Cascade Reactions for the Synthesis of Polycyclic Aromatic Hydrocarbons and Carbon Nanoribbons Philip M

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2013 Cascade Reactions for the Synthesis of Polycyclic Aromatic Hydrocarbons and Carbon Nanoribbons Philip M. Byers

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COLLEGE OF ARTS AND SCIENCES

CASCADE REACTIONS FOR THE SYNTHESIS OF POLYCYCLIC AROMATIC

HYDROCARBONS AND CARBON NANORIBBONS

PHILIP M. BYERS

A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy

Degree Awarded: Summer Semester, 2013 Philip Byers defended this dissertation on June 17, 2013. The members of the supervisory committee were:

Igor V. Alabugin Professor Directing Dissertation

Rufina Alamo University Representative

Geoffrey Strouse Committee Member

Sourav Saha Committee Member

The Graduate School has verified and approved the above-named committee members, and certifies that the dissertation has been approved in accordance with university requirements.

To Loretta Jacqueline Jahoda Your patience, love and strength are an inspiration to me every day.

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ACKNOWLEDGMENTS

This body of work would not have been possible without the support and guidance of my professors, peers, friends and family. After moving from western New York to Tallahassee in 2008, it has been a blessing to meet so many amazing people that have helped me succeed in my graduate career at Florida State. I would like to acknowledge my advisor, Professor Igor V. Alabugin, for accepting me into his group and supporting me during my research at FSU. Without his teachings and advice, the discoveries made during my graduate career would not have been possible. I have also had the opportunity to work with a number of amazing research scientists in my lab that helped shape me into the scientist I am today. I am grateful to Dr. Raja Angamuthu, Dr. Samuya Roy, Dr. Nikolay Shevchenko, Dr. Sergei Emets, Dr. Sayantan Mondal, Dr. Kishore Pati and especially Dr. Runa Pal who helped train me when I first joined the group. I would also like to recognize my labmates current and past, Dr. Jason Abrams, Dr. Wang-Yong Yang, Dr. Kerry Gilmore, Dr. Paul Peterson, Brian Gold, Kemal Kaya, Rana Mohamed, Trevor Harris, Audrey Hughes and Matthew Dickman. They have made coming to the lab every day an enjoyable experience. I have also had the opportunity to meet and learn from a number of great scientists at FSU. I would like to especially recognize Dr. Marilda Lisboa, Dr. David Jones, Dr. Umesh Goli, Dr. Tania Houjeiry, Steven Freitag, Michael Rosana, and Dr. Tyler Simmons for great technical and academic discussions. The undergraduate researchers that worked with me were also very influential in the success of my projects, including Julian Rashid, Ilya Piskun, Vekarius Barnes, Sheeva Yazdani, Artem Bobylev and Audrey Smith. I also have had the opportunity to meet a number of amazing people in Tallahassee who made my time here unforgettable, especially Jessica McBride, Kyle Rininger, Catherine Callahan, and pretty much the whole crew over at Momo’s pizza. Most importantly I have to thank my family, Richard and Kimberly, and my sisters Lindsay and Jessica, who without their support financially and otherwise, this would not have been possible. Thank you for your unwavering belief in me throughout my graduate career and all of my endeavors.

TABLE OF CONTENTS

List of Tables ...... vii List of Figures ...... viii Abstract ...... xviii 1. INTRODUCTION TO RADICAL CASCADE REACTIONS ...... 1 1.1 Radical Cascades ...... 1 1.1.1 Cascade Reactions by Chain Radical Processes ...... 1 1.1.2 Radical Cascade Reactions Involving Non-Chain Redox Processes ...... 9

2. POLYAROMATIC RIBBONS FROM OLIGO-ALKYNES VIA SELECTIVE RADICAL CASCADE: STITCHING AROMATIC RINGS WITH POLYACETYLENE BRIDGES ...... 14 2.1 Background ...... 14 2.2 Enediyne Synthesis and Radical Cascades ...... 17 2.3 Tetrayne Synthesis and Radical Cascades ...... 23 2.4 Conclusion and Future Work ...... 26

3. ELECTROPHILE-PROMOTED NUCLEOPHILIC CLOSURE CASCADE REACTIONS THROUGH GOLD CATALYSIS ...... 29 3.1 Introduction ...... 29 3.2 Examples of Gold Catalysis used for Cascade Reactions ...... 31 3.3 Examples of Gold Catalyzed Hydroarylation Reactions ...... 36 3.4 Synthesis of Polycyclic Aromatic Hydrocarbons through Gold Catalyzed Cascade Reactions Initiated by Hydroamination Cyclizations ...... 40

4. GOLD CATALYSED CASCADE REACTION OF ENEDIYNES AND TRIYNE FOR THE SYNTHESIS OF FUSED BENZOFURAN POLYCYCLIC AROMATIC HYDROCARBONS ...... 45 4.1 Introduction ...... 45 4.2 Gold Catalyzed Cascade of Enediynes and Triyne ...... 45 4.3 Conclusions ...... 53

5. FUTURE WORK AND CONCLUSIONS ...... 54 5.1 Future Work ...... 54 5.2 Conclusions ...... 60

APPENDICES ...... 62

A. EXPERIMENTAL DETAILS FOR RADICAL CASCADE (CH. 2) ...... 62

B. COMPUTATIONAL COORDINATES FOR RADICAL CASCADE (CH. 2) ...... 73

C. NMR SPECTRA OF STARTING MATERIALS AND CASCADE PRODUCTS (CH. 2) ...... 116

D. EXPERIMENTAL DETAILS FOR GOLD CATALYZED CASCADE AND OPTIMIZED COORDINATES OF 21 (CH. 4) ...... 165

E. NMR SPECTRA OF STARTING MATERIALS AND CASCADE PRODUCTS (CH. 4) ...... 178

REFERENCES ...... 217

BIOGRAPHICAL SKETCH ...... 227

LIST OF TABLES

1 Computational analysis of enediyne cascade (B3LYP/6-31+ (d, p)), kcal/mol...... 22

2 Optimization of the catalyst system...... 49

3 Tandem Sonogashira/cascade of substituted enediynes...... 50

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LIST OF FIGURES

1 Stereoselective radical cascade as a key step in the construction of AB rings of azadirachtin...... 3

2 Intermolecular iodine atom transfer cascades of alkynes to form vinyl iodides...... 4

3 Access to polycyclic indoles by radical addition/cyclization...... 5

4 O-neophyl rearrangement/fragmentation cascade for the conversion of phenols into benzoates and benzamides...... 6

5 Radical cyclization strategies to access complex polycyclic frameworks...... 8

6 Radical/aldol sequence from dialdehyde compounds using SmI2...... 10

7 Carbodiazenylation of alkenes from aryldiazonium salts using TiCl3...... 11

8 Mn(III)-promoted 5-exo/6-endo radical cyclization reactions...... 12

9 B3LYP calculated barriers for radical cascade transformation of tris-o- aryleneethynylenes via selective intermolecular activation...... 15

10 Proposed extension of the alkyne radical cascade towards longer graphene ribbons and importance of selective radical attack at the central alkyne...... 16

11 Synthesis of enediyne compounds for model radical cascade reactions...... 18

12 Optimization of cascade conditions...... 18

13 HSQC and HMBC experiments for the cyclization of p-OMe-substituted enediyne 2d...... 20

14 Yields and potential energy surfaces for the cascade cyclization of substituted enediynes (B3LYP/6-31+(d,p), kcal/mol)...... 21

15 a) HMBC NMR correlations used to establish the structure of cascade product 13a and b) H and C chemical shifts for cascade product 13a...... 24

16 Synthesis of o-aryleneethynylene tetramers and the proposed mechanism of cascade transformation...... 25

17 Relative energies and structures of intermediates for the cascade radical transformation of tetraynes (B3LYP/6-31+G(d,p), kcal/mol). HOMO and LUMO for the final product 13b are given on top...... 26

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18 Conceptual approaches for the use of alkyne functionality in preparation of graphene ribbons...... 27

19 Alkynes behaving as a) nucleophiles in which they coordinate to metal centers like Au and as b) electrophiles in which the alkyne is attacked from methoxy anion to form methyl vinyl ether...... 30

20 Formation of gold (I)-alkynyl complexes B and dual π-coordinated/gold-alkynyl-σ-bond complex C...... 30

21 The fundamental reactivity pattern in gold catalysis...... 31

22 Reaction conditions for gold(I)-catalyzed reaction of alkynoic acids. (a) AuPPh3Cl/AgOTf (1 mol %), toluene, rt, 71%; (b) AuPPh3/AgOTf (1 mol %), toluene, reflux, 68%; (c) AuPPh3Cl/AgOTf (1 mol %), toluene, rt, 3 h then reflux, 2 days, 81%. 32

23 Synthesis of complex α-pyrones by a gold-catalyzed cascade reaction...... 33

24 Gold (I) catalyzed alkynylation/cyclization...... 34

25 Mechanism for the gold(I)-catalyzed cascade alkynylation/cyclization...... 35

26 Synthesis of pyrrolo[1,2-a]quinolin-1(2H)-ones...... 35

27 Catalytic cycle for the synthesis of pyrrolo[1,2-a]quinolin-1(2H)-ones catalyzed by AuBr3/AgSbF6...... 36

28 Intermolecular addition of benzene to 1,2-dialkynylarenes toward naphthalene derivatives...... 37

29 Mechanistic model to explain the formation of β-phenylnaphthalenes through dual Au activation...... 38

30 Synthesis of 1,2 and 1,3 substituted naphthalenes through metal catalyzed hydroarylation reactions...... 39

31 a) Plausible catalytic cycle for the formation of 1,3 disubstituted naphthalenes through gold catalysis. b) Reaction of silyl enol ether G under standard reaction conditions to confirm that the reaction pathway proceeds through intermediate D...... 40

32 Synthesis of aryl-annulated fused indoles...... 41

33 Effect of various arene tethers on gold catalyzed cascade reaction...... 42

34 a) Proposed reaction mechanism for gold catalyzed cascade reaction for the synthesis of fused carbazoles. b) Cyclization of intermediate G using standard reaction conditions. .43

35 a) Tetrayne and b) Pentayne synthesis of fused complex carbazole structures...... 44

36 Preferred trajectories for alkyne cyclizations and the possible switch from the “all-exo” radical cascade to the “all-endo” metal-assisted cascade...... 47

37 Synthesis of enediynes...... 47

38 Au-assisted 6-endo-dig cyclization...... 51

39 Triyne synthesis and cascade reaction with 2-iodophenol (A) and comparison of “all-exo” and “all-endo” strategies towards the preparation of graphene ribbons (B)...... 52

40 Comparison of gold catalyzed electrophile-promoted nucleophilic ring closure cascades for the goal of designing an all 6-endo-dig cascade process...... 55

41 Examples of 6-endo hydroarylation reactions through ruthenium catalysis...... 56

42 Iodine promoted hydroarylations for the synthesis of poly-heterocyclic structures...... 57

43 Gold catalysis promotes 6-endo-dig hydroarylation over 5-exo-dig hydroarylation...... 58

44 Synthesis of starting materials for gold catalyzed hydroarylation cascade incorporating donor and acceptor substituents to promote consumption of all alkynes present...... 59

45 Synthesis of PAH and carbon nanoribbons through gold catalyzed hydroarylation cascade and Scholl or Mallory oxidative ring closing reactions...... 60

46 1H NMR spectra of 1-(2-bromoethoxy)-2,3-diiodobenzene...... 116

47 13C NMR spectra of 1-(2-bromoethoxy)-2,3-diiodobenzene...... 117

48 1H NMR spectra of 1a...... 117

49 13C NMR spectra of 1a...... 118

50 1H NMR spectra of 1b...... 118

51 13C NMR spectra of 1b...... 119

52 1H NMR spectra of 1c...... 119

53 13C NMR spectra of 1c...... 120

54 1H NMR spectra of 1d...... 120

55 13C NMR spectra of 1d...... 121

56 1H NMR spectra of 1e...... 121

57 13C NMR spectra of 1e...... 122

58 1H NMR spectra of 1f...... 122

59 13C NMR spectra of 1f...... 123

60 1H NMR spectra of 1g...... 123

61 13C NMR spectra of 1g...... 124

62 1H NMR spectra of 3...... 124

63 13C NMR spectra of 3...... 125

64 1H NMR spectra of 11a...... 125

65 13C NMR spectra of 11a...... 126

66 1H NMR spectra of 12a...... 126

67 13C NMR spectra of 12a...... 127

68 1H NMR spectra of 11b...... 127

69 13C NMR spectra of 11b...... 128

70 1H NMR spectra of 12b...... 128

71 13C NMR spectra of 12b...... 129

72 1H NMR spectra of 11c...... 129

73 13C NMR spectra of 11c...... 130

74 1H NMR spectra of 12c...... 130

75 13C NMR spectra of 12c...... 131

76 1H NMR spectra of 11d...... 131

77 13C NMR spectra of 11d...... 132

78 1H NMR spectra of 12d...... 132

79 13C NMR spectra of 12d...... 133

80 1H NMR spectra of 2a...... 133

81 13C NMR spectra of 2a...... 134

82 COSY NMR spectra of 2a...... 134

83 1H NMR spectra of 2b...... 135

84 13C NMR spectra of 2b...... 135

85 COSY NMR spectra of 2b...... 136

86 1H NMR spectra of 2c...... 136

87 13C NMR spectra of 2c...... 137

88 COSY NMR spectra of 2c...... 137

89 1H NMR spectra of 2d...... 138

90 13C NMR spectra of 2d...... 138

91 gHSQC NMR spectra of 2b. Important direct C-H couplings are shown with colored circles. Numbers on cascade product correspond to the following C,H couples. 1: (7.25, 114.2 ppm), 2: (6.92, 126.5 ppm), 3: (6.76, 116.5 ppm), 4: (4.30, 67.2 ppm), 5: (2.96, 25.3 ppm), 6: (7.34, 158.9 ppm), 7: (6.96, 113.79 ppm), 8: (3.87, 55.3 ppm), 9: (7.19, 134.1 ppm), 10: (7.53, 159.7 ppm), 11: (7.00, 113.8 ppm), 12: (3.88, 55.3 ppm)...... 139

92 1H and 13C chemical shifts determined by 2D NMR for compound 2d...... 139

93 HMBC NMR spectra of 2b. a) Full spectrum. b) Aromatic region...... 140

94 gCOSY spectrum of 2d shows hydrogen correlations in the methoxy-substituted benzene rings and also correlation between CH2’s of the –OCH2CH2- moiety...... 142

95 1H NMR spectra of 2e...... 143

96 13C NMR spectra of 2e...... 143

97 HSQC NMR spectra of 2e...... 144

98 1H and 13C chemical shifts determined by 2D NMR for compound 2e...... 144

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99 HMBC NMR spectra of 2e...... 145

100 COSY NMR spectra of 2e...... 146

101 The stereochemistry of 2e was determined by 1D nOe experiment...... 146

102 1H NMR spectra of 2f...... 147

103 13C NMR spectra of 2f...... 148

104 COSY NMR spectra of 2f...... 148

105 1H NMR spectra of 4...... 149

106 13C NMR spectra of 4...... 149

107 1H NMR spectra of 5...... 150

108 13C NMR spectra of 5...... 150

109 1H NMR spectra of 13a...... 151

110 13C NMR spectra of 13a...... 151

111 Full HSQC NMR spectra of 13a...... 152

112 Full HMBC NMR spectra of 13a...... 152

113 HSQC NMR spectra of 13a for aliphatic and aromatic regions...... 153

114 HMBC NMR spectra of 13a for aliphatic and aromatic regions...... 154

115 1H and 13C chemical shifts determined by 2D NMR for compound 13a...... 155

116 1H NMR spectra of 13a2...... 156

117 13C NMR spectra of 13a2...... 156

118 1H NMR spectra of 13b...... 157

119 13C NMR spectra of 13b...... 157

120 Full HSQC NMR spectra of 13b...... 158

121 Full HMBC NMR spectra of 13b...... 158

xiii

122 HSQC NMR spectra of 13b aliphatic region...... 159

123 HSQC NMR spectra of 13b aromatic region...... 159

124 HMBC NMR spectra of 13b aliphatic region...... 160

125 HMBC NMR spectra of 13b aromatic region...... 160

126 1H NMR spectra of 13c...... 161

127 13C NMR spectra of 13c...... 161

128 Full HSQC NMR spectra of 13c...... 162

129 Full HMBC NMR spectra of 13c...... 162

130 HSQC NMR spectra of 13c aliphatic region...... 163

131 HSQC NMR spectra of 13c aromatic region...... 163

132 HMBC NMR spectra of 13c aliphatic and aromatic regions...... 164

133 1H NMR spectra of 16a...... 178

134 13C NMR spectra of 16a...... 179

135 1H NMR spectra of 16b...... 179

136 13C NMR spectra of 16b...... 180

137 1H NMR spectra of 16c...... 180

138 13C NMR spectra of 16c...... 181

139 1H NMR spectra of 16d...... 181

140 13C NMR spectra of 16d...... 182

141 1H NMR spectra of 16e...... 182

142 13C NMR spectra of 16e...... 183

143 1H NMR spectra of 16f...... 183

144 13C NMR spectra of 16f...... 184

xiv

145 1H NMR spectra of 16g...... 184

146 13C NMR spectra of 16g...... 185

147 1H NMR spectra of 16h...... 185

148 13C NMR spectra of 16h...... 186

149 1H NMR spectra of 16i...... 186

150 13C NMR spectra of 16i...... 187

151 1H NMR spectra of 16j...... 187

152 13C NMR spectra of 16j...... 188

153 1H NMR spectra of 17a...... 188

154 13C NMR spectra of 17a...... 189

155 1H NMR spectra of 17b...... 189

156 13C NMR spectra of 17b...... 190

157 1H NMR spectra of 17c...... 190

158 13C NMR spectra of 17c...... 191

159 1H NMR spectra of 17d...... 191

160 13C NMR spectra of 17d...... 192

161 1H NMR spectra of 17e...... 192

162 13C NMR spectra of 17e...... 193

163 1H NMR spectra of 17f...... 193

164 13C NMR spectra of 17f...... 194

165 1H NMR spectra of 17g...... 194

166 13C NMR spectra of 17g...... 195

167 1H NMR spectra of 17h...... 195

168 13C NMR spectra of 17h...... 196

169 1H NMR spectra of 17i...... 196

170 13C NMR spectra of 17i...... 197

171 1H NMR spectra of 17j...... 197

172 1C NMR spectra of 17j...... 198

173 1H NMR spectra of 18a...... 198

174 13C NMR spectra of 18a...... 199

175 1H NMR spectra of 18b...... 199

176 13C NMR spectra of 18b...... 200

177 1H NMR spectra of 18c...... 200

178 13C NMR spectra of 18c...... 201

179 1H NMR spectra of 18d...... 201

180 13C NMR spectra of 18d...... 202

181 1H NMR spectra of 18e...... 202

182 13C NMR spectra of 18e...... 203

183 1H NMR spectra of 18f...... 203

184 13C NMR spectra of 18f...... 204

185 1H NMR spectra of 18h...... 204

186 13C NMR spectra of 18h...... 205

187 1H NMR spectra of 18i...... 205

188 13C NMR spectra of 18i...... 206

189 1H NMR spectra of 18j...... 206

190 13C NMR spectra of 18j...... 207

xvi

191 1H NMR spectra of 19...... 207

192 13C NMR spectra of 19...... 208

193 1H NMR spectra of 20...... 208

194 13C NMR spectra of 20...... 209

195 1H NMR spectra of 21...... 209

196 13C NMR spectra of 21...... 210

197 HSQC NMR spectra of 18a...... 211

198 HMBC NMR spectra of 18a...... 212

199 1H and 13C chemical shifts determined by 2D NMR for compound 18a...... 213

200 Full HSQC NMR spectra of 21...... 213

201 HSQC NMR spectra of 21 aromatic region...... 214

202 Full HMBC NMR spectra of 21...... 215

203 HMBC NMR spectra of 21 aromatic region...... 215

204 1H and 13C chemical shifts determined by 2D NMR for compound 21...... 216

xvii

ABSTRACT

Radical and electrophile-promoted nucleophilic closure cascade reactions have been used for the synthesis of polycyclic aromatic hydrocarbons (PAHs) and carbon nanoribbons. Chapter 1 provides a discussion on radical cascade reactions, with a brief history and examples of well documented radical cascade reactions. Investigations into radical chain processes as well as redox processes are discussed. There is much development in these cascades currently due to the complex products that can be formed in a minimal amount of synthetic steps. Chapter 2 discusses the radical cascade that we developed, using a radical chain process. Selective radical generation in conjugated oligomeric o-aryleneethynylenes initiates a cascade which involves five fast radical cyclizations followed by aromatization via a 1,5-H shift to yield PAHs. Computation and 2D NMR studies were performed to determine the final cascade products. Chapter 3 discusses the growing trend in which gold catalysts are used to initiate cascade reactions through an electrophile-promoted nucleophilic closure mechanism. A number of current examples are also provided which demonstrate how gold catalyzed cascade reactions can efficiently synthesize complex PAH molecules. Chapeter 4 demonstrates our approach for the synthesis of fused benzofuran structures through gold catalysis. Through a gold catalyzed electrophile-promoted nucleophilic closure, PAHs containing benzofuran units with a polycyclic aromatic backbone were synthesized through a Sonogashira/5-endo-dig/6-endo-dig cascade. Depending on which mechanism is used, all exo cyclizations can be achieved (radical), or all endo cyclizations (electrophile-promoted nucleophilic closure). Starting materials for either cascade mechanism can be synthesized in a modular fashion, allowing for the systematic and controlled preparation of functionalized PAHs and carbon nanoribbons where, potentially, each of the peripheral aromatic rings can be different. The materials synthesized have future applications in the nano-materials and –electronics industries. Chapter 5 discusses future work in the field of gold catalyzed cascade reactions and provides conclusions on the work presented here within.

xviii

CHAPTER ONE

INTRODUCTION TO RADICAL CASCADE REACTIONS

1.1 Radical Cascades

“Cascade” radical reactions, also known as “tandem” or “domino” radical radical reactions, proceed through two or more consecutive steps under involvement of both intra- and intermolecular reactions. Radical cascades are synthetically very attractive because they enable access to highly complex and often polycyclic molecular frameworks in only a few synthetic steps. Employed in numerous syntheses of natural products,1 they embody control over chemical reactivities. Furthermore, they contribute to progress toward green chemistry since they allow a large increase in molecular complexity in a minimum of steps, and hence avoid waste generation.

The usually mild conditions of radical reactions are compatible with many functional groups so that time-consuming protection strategies can be minimized. Because of the excellent stereo-2 and enantiocontrol3 in radical reactions, complex structures can be synthesized in a minimum number of steps. Organic radicals are thus tools of choice for the development of efficient and selective cascade reactions as illustrated by the large number of applications reported in the literature.4,5,6,7,8

1.1.1 Cascade Reactions by Chain Radical Processes

The majority of radical cascades involve sequences of intramolecular steps when the overall propagation is a unimolecular process, with exclusion of the initiation and termination steps. In addition, tandem radical procedures that involve a combination of intra- and intermolecular steps

1 or are even multicomponent reactions have also been developed.9,10 Cascade reactions that are initiated by intermolecular addition of both carbon- and heteroatom-centered radicals to π systems have predominantly been explored with C=C, C=N, and C=O double bonds acting as radical acceptors.11,12 However there are not as many examples of intermolecular attack on sp carbons such as C≡C or C≡N due to the relatively low stability of the intermediate vinyl radicals.13,14

Poly 5- or 6-exo cyclizations are the most straightforward strategies for the construction of polycyclic frameworks. In a synthetic study toward azadirachtin, Wantanabe employed a cascade involving 5-exo-dig/6-exo-trig radical cyclization using a tetra-substituted allene and α,β- unsaturated lactone as radical acceptors.15 The rigidity of the spirolactone ring embedded in the precursor seemed to favor the cyclization and allowed the synthesis of the two key carbocycles of the target molecule in a diastereoselective manner and with an excellent 90% yield (Figure 1).

An efficient synthesis of angularly fused carbocycles by a combination of 5-exo-dig and 5-exo- trig cyclizations was described by Mohanakrishnan.16

Alkyl iodides are common precursors in the formation of carbon-centered radicals as iodine is most easily abstracted by Sn or Si radicals due to the weakness of the C-I bond. In radical reactions, iodine can also be transferred to a different part of the molecule and serve as an activating group in additional couplings. The intermolecular iodine atom transfer addition of alkyl iodides to alkynes has been used to access vinyl iodides,17 as well as in radical cascade processes under radical-chain conditions.

Figure 1. Stereoselective radical cascade as a key step in the construction of AB rings of azadirachtin.

Curran et al. described a procedure that involves a radical-mediated addition of alkyl iodides to alkynes at the final stage of the sequence (Figure 2a). Cyclohexenyl-substituted alkyl

˙ radicals C generated from the corresponding iodide A using tin radicals (Bu3Sn ) as the initiator

undergo first a cis selective 5-exo cyclization to yield cyclohexyl-derived radicals D. The latter

are subsequently trapped from the sterically less congested convex side through intermolecular

addition to the alkyne terminus of methyl propiolate. Reaction of the vinyl radical intermediate E

with the starting material A in a chain-propagation step gives bicyclic vinyl iodide B as E/Z

mixture (the E/Z ratio was not determined).18 Oshima et. al. used triethylborane to initiate a

conjugate addition of tert-butyl iodide to enyne F to access 2,3,4-trisubstituted tetrahydrofurans

G as mixture of E/Z isomers (Figure 2b). The cascade proceeds via first regioselective addition

of the nucleophilic tert-butyl radicals, t-Bu˙, to the sterically less hindered alkyne π system in F, followed by 5-exo cyclization of vinyl radical H and iodine abstraction by the cyclized radical intermediate I.19

(a) Curran et al. CO2Me CO2Me I I (Bu3Sn)2 (10%) H

C6H6, hv, reflux A H B 14% C

Bu3Sn Bu SnI 3 A CO2Me

H H 5-exo CO2Me

H H C D E

(b) Oshima et al. t-BuI

Et3B (0.5 equiv) t-Bu O O hexane, 60 oC n-Bu n-Bu F G I 42%

t-Bu t-BuI

t-Bu 5-exo O O

n-Bu n-Bu HI

Figure 2. Intermolecular iodine atom transfer cascades of alkynes to form vinyl iodides.

Xanthates have also been reported to initiate cascades through a radical chain process. Zard reported the formal synthesis of mersicarpine through an intermolecular radical

addition/cyclization cascade.20 Activation of an indole xanthate (such as A, Figure 3) by lauroyl peroxide allows the addition of the resulting carbon-centered radical on a terminal olefin, delivering the intermediate B, which then undergoes 6-exo-trig cyclization at the indole ring C.

This radical led to the products D and E, obtained either through disproportionation or by hydrogen abstraction by additional lauroyl peroxide. The authors reported that the presence of an electron-withdrawing carboxylate substituent at the 3-position of the heterocycle is crucial for the process, suggesting that the reversibility of the radical addition onto the indole could be overcome by proper stabilization of the intermediate C.

Figure 3. Access to polycyclic indoles by radical addition/cyclization.

The thiocarbonyl group of xanthates is an excellent functional group for the formation of carbon centered radicals for cascade reactions but can also be useful for selective rearrangements

in the presence of different functional groups. A recent report for the metal-free transformation

of phenols into benzoates21 and benzamides22 was designed to proceed through an O-neophyl rearrangement/fragmentation cascade. Diaryl thiocarbonates and thiocarbamates, available in a single high yielding step from phenols, selectively add silyl radicals at the sulfur atom of the

C=S moiety. This addition step, analogous to the first step of the Barton-McCombie reaction, produces a carbon radical which undergoes 1,2 O→C transportation through an O-neophyl rearrangement. The usually unfavorable equilibrium in the reversible rearrangement step is shifted forward via a highly exothermic C-S bond scission in the O-centered radical, which furnishes the final benzoic ester or benzamide product (Figure 4).23

Figure 4. O-neophyl rearrangement/fragmentation cascade for the conversion of phenols into benzoates and benzamides.

Radical cyclization cascades have proven to be excellent strategies for the formation of complex polycyclic frameworks in one step with excellent stereocontrol. It is not surprising that this strategy has been used as the key steps in a number of natural product syntheses24 as radicals have orthogonal reactivity to a number of common functional groups. In the total synthesis of the pentacyclic sesquiterpene (±)-merrilactone A by Frontier et al., the core tricyclic motif B was

produced through regioselective 5-exo cyclization of the initially formed nucleophilic vinyl radical to the less electron-rich π system in the dihydrofuranone ring in dienyne A (Figure 5a).25

Similar polar effects were also used by Kaliappan et al. to direct the 5-exo cyclization of the

vinyl radical formed after addition of Sn-radicals to the alkyne moiety in C. The resulting product D was subsequently transformed into the oxatetracyclic compound E, which is a core

structure of antibiotic platensimycin (Figure 5b).26 In order to access the structural isowistane core motif H of the fungal metabolite CP-263114 (structure not shown), a 5-exo vinyl radical cyclization onto a carbonyl group was used by Wood et al. to transform the tricyclic enynone F into the tetracyclic species G (Figure 5c).27 The tricyclic ring system in (-)-4a,5- dihydrostreptazolin was generated by Cossy et al. from the propargyl alcohols I using a cascade consisting of Sn-radical addition and cis selective 5-exo cyclization J (Figure 5d).28 The heptacyclic framework of the hetisine-type aconite alkaloid (±)-nominine has been synthesized by Muratake and Natsume through a 6-endo vinyl radical cyclization following Sn-radical addition to the alkyne terminus in K (Figure 5e).29 Apart from the desired major product L, small

amounts of a product that results from competing 5-exo-cyclization were also obtained (not shown).

Figure 5. Radical cyclization strategies to access complex polycyclic frameworks.

1.1.2 Radical Cascade Reactions Involving Non-Chain Redox Processes

It has been well documented that a number of transitions metals can initiate radical cascade reactions through one electron transfer redox processes. For example, samarium diiodide became a popular reducing agent in organic synthesis since its discovery by Kagan in 1977.30 This one- electron-transfer reagent has been largely used due to its high reactivity under mild conditions and the generally high chemoselectivity. Moreover, SmI2 is known to induce either radical or ionic processes. Procter reported “radical then aldol” cyclization cascades from dialdehyde substrates A, leading to tricyclic products B (Figure 6).31 The reduction of one of the aldehydes afforded the corresponding ketyl radical anion C, which underwent an anti-selective 5-exo-trig radical cyclization onto the activated olefin with the formation of samarium enolates. By chelation to samarium (III), a diastereoselective aldol cyclization involving a six-membered transition structure D occurred and the final tricyclic compound B was obtained. Precoordination of samarium to the ester would favor the reduction of the nearer aldehyde selectively, thus explaining the difference in reactivity between the two aldehyde groups. This methodology has been applied by the same group to an original approach to pleuromutilin.32

Figure 6. Radical/aldol sequence from dialdehyde compounds using SmI2.

Titanium complexes have also been well documented for promoting radical cascade reactions, as they are remarkable single-electron reductive reagents. As reported by Heinrich, carbodiazenylation of non-activated olefins can be accomplished with aryl-diazonium salts in the

33 presence of TiCl3. The reduction of the diazonium salt by Ti (III) generates an aryl diazenyl radical. After nitrogen extrusion, the liberated aryl radical can add to the olefin to form an intermediate alkyl radical, which then reacts with a second equivalent of diazonium salt. The resulting aminyl radical cation is finally reduced to the azo compound (Figure 7). This process allowed carbodiazenylation of nonactivated alkenes. Neither dry solvents nor an inert atmosphere were needed. The carbodiazenylation was then extended to aliphatic derivatives through initial radical iodine atom transfer reactions of iodoacetonitrile and iodoacetate with the olefin.34

Figure 7. Carbodiazenylation of alkenes from aryldiazonium salts using TiCl3.

While titanium (III) salts are able to induce radical cascade cyclizations through reductive processes, manganese (III) salts are able to induce similar cascade reactions but through oxidative processes. In 2006, Chen disclosed an efficient synthesis of various polycyclic core skeletons of natural products such as ageliferin or massadine, involving Mn (III)-mediated oxidative heterobicyclizations leading to the formation of two C-C bonds and three stereogenic

35 centers. The treatment of allylic β-imidazolinonyl-β-ketoesters with Mn(OAc)3 produced lactone tricyclic compounds by either a 5-exo-trig/6-endo-trig or a 5-exo-trig/5-exo-trig cascade radical cyclization. The regioselectivity depends on the substitution of the imidazolinonyl ring.

For instance, the allylic β-imidazolinonyl-β-ketoester A is first oxidized by the Mn (III) salt to form a radical species, which then cyclizes cleanly into the tricycle B. The resulting radical was

oxidized by another equivalent of Mn(III) and a proton was eliminated (Figure 8). Most of the

transformations were performed with good yields and regio- and diastereoselectivities.

O O NBn BnN BnN NBn Mn(OAc)3 H O O AcOH, 60 oC H O 63% O O O A

Mn(III) Mn(III) -H+

O O NBn BnN NBn BnN H 5-exo/6-endo-trig O O H O O O B O

Figure 8. Mn (III)-promoted 5-exo/6-endo radical cyclization reactions.

A number of other transition metals can induce radical cascade reactions through redox

processes including Fe,36,37 Cu,38,39 Zn,40,41 Ag,42,43 and Ce. Cerium ammonium nitrite (CAN) is the most commonly used reagent in these types of reactions.44,45

1.2 Conclusions

These given examples demonstrate that intra- and intermolecular radical addition to alkynes is a very powerful synthetic methodology for initiation of radical cascade processes that lead to complex structural frameworks with excellent stereo- and regiocontrol under mild conditions.

The success of these cascades is due to the initially formed highly reactive vinyl radicals rapidly

12 undergo intra- or intermolecular reactions. Radical addition to C-C triple bonds is the most convenient way for the generation of vinyl radicals.

Initial radical addition to the alkyne is highly regioselective and in reactions with substrates possessing several π systems, for example, enynes and dienynes, the alkynes moiety is usually attacked with high preference. Due to their high reactivity, vinyl radicals that are formed through radical attack at the alkyne moiety in enynes, for example, are rapidly and irreversibly trapped through subsequent reactions. In contrast to this, alkyl radicals resulting from radical addition to an alkene are far less reactive so that the competing dissociation and regeneration of the starting materials is often faster than the forward reaction steps. The knowledge of this radical cascade precedence is of fundamental importance for successful design of a new cascade reaction that is triggered by radical addition to alkynes.

CHAPTER TWO

POLYAROMATIC RIBBONS FROM OLIGO-ALKYNES VIA SELECTIVE RADICAL CASCADE: STITCHING AROMATIC RINGS WITH POLYACETYLENE BRIDGES

2.1 Background

Interest in polycyclic aromatic hydrocarbons (PAHs) was refuelled by their structural relation to graphene, a form of carbon whose mechanical and electronic properties46,47 are distinctly different from those other carbon nanostructures.48 Because structural variations (e.g., size, shape, curvature,49 edge geometry50 and composition51) affect electronic properties strongly, progress in this field depends on the development of rationally designed “bottom-up”52 approaches towards chemically and structurally uniform graphene substructures. While a number of elegant approaches53 to the design of symmetric graphene nanoribbons have been reported, efficient and flexible approaches to non-symmetrically substituted graphene nanoribbon structures are scarce.54,55,56 These approaches become even more valuable considering recent reports where relatively large polycyclic aromatic hydrocarbons were used to create even larger carbon nanostructures using surface-assisted coupling57 and template-initiated growth.58

Alkyne functionality is an attractive entry point for the preparation of carbon-rich materials59 due to its high carbon content (atom economy), the possibility of modular assembly via reliable cross-coupling chemistry, and the propensity of alkynes to participate in well- choreographed cascade transformations leading to the rapid construction of polycyclic frameworks.60 These advantages are illustrated by the recently reported radical cascade transforming triynes (1,2-bis(2-arylethynyl)phenyl ethynes) into an extended polyaromatic 14

system (benzo[a]indeno[2,1-c]fluorene) in >70%.61 The efficiency of this cascade hinges on the chemoselective intermolecular attack of tributyl tin (Bu3Sn) radical at the central alkyne of the

triyne system (Figure 9). This step initiates an efficient cascade, where each of the subsequent

steps (5-exo-dig, 6-exo-dig cyclizations, attack at the aromatic ring and 1,5-shift-induced

rearomatization) has a low barrier following a favorable energy landscape to progressively more

and more stable intermediates.

Intermolecular attack R at the central alkyne R R

Bu3SnH, AIBN

X X 1. 1,5-H shift R X=H, R=H, CH : X=SnBu 2. H-abstraction 3 3 >70% 3. Destannylation (HCl, CH2Cl2) R R R A A A R R 4 R D D D 3 3 B B B 2 2 2 C C C X 1 X 1 X 1

Ea=3.2 kcal/mol Ea=5.9 kcal/mol Ea=12.3 kcal/mol

Figure 9. B3LYP calculated barriers for radical cascade transformation of tris-o- aryleneethynylenes via selective intermolecular activation.

Mechanistic studies together with DFT computational analysis revealed the reasons for this

efficiency and suggested that this cascade can be expanded to the preparation of larger molecules

of different sizes and architectures. In particular, we were encouraged by the lower calculated

barriers for the key 5-exo-dig and 6-exo-dig cyclization steps62 (~3 and ~6 kcal/mol,

respectively) relative to the barrier for the final ring formation via radical attack at an aromatic

system (12 kcal/mol, Figure 9). According to these values, the final cyclization step is ~100,000

times slower than the 6-exo-dig closure on the pendant alkyne. The energetics suggests that if the starting material had additional triple bonds capable of extending the cascade, preparation of larger carbon nanostructures would be feasible.

However, when we applied intermolecular initiation to the longer polymers, the selectivity decreased dramatically and complex mixtures were formed.63 For this cascade to go to

completion, the radical cascade must be initiated via selective attack at the central alkyne.

Attack at any other alkyne would require an unfavorable cascade that involves a relatively

inefficient64 5-endo (or 4-exo) closure (Figure 10).

Figure 10. Proposed extension of the alkyne radical cascade towards longer graphene ribbons and importance of selective radical attack at the central alkyne. 16

2.2 Enediyne Synthesis and Radical Cascades

The similarity of electronic and steric properties of alkynes in the larger polyalkyne oligomers precludes selective intermolecular radical attack at the central alkyne. We describe here a strategy that targets the central alkyne by intramolecular radical attack. A suitable initiator

(the “weak link”) is built-in directly at the central ring to ensure that the cascade begins at the right part of the molecule. Selective radical formation in the presence of multiple triple bonds initiates the complete “zipping” of the oligo alkynes into a fully aromatic ribbon.

Since radical cascades are often compatible with a variety of functional groups,58 we have concentrated on radical initiation of the cascade. Because finding suitable conditions for the chemoselective alkyl radical generation in the presence of multiple alkynes is challenging, we turned to model compounds with two triple bonds (enediynes).

We chose the first intramolecular step in the radical cascade to 6-exo-dig closures to avoid the unfavorable arrangement of two fused five-membered rings.60c The requisite library of enediynes was synthesized through the Sonogashira reaction of 1-(2-bromoethoxy)-2,3- diiodobenzene with a number of substituted alkynes 1a-1e. Bis-1-naphthyl enediyne 1g was prepared through a slightly different procedure based on Sonogashira coupling of the terminal enediyne 1f with 1-iodonaphthalene (Figure 11).

Our initial efforts using triethylsilane and tris(trimethylsilyl)silane (Et3SiH and TTMSS) led to the products of the desired cascade transformation. However, the reactions were sluggish and the yields were low (21-25%). A dramatic increase in efficiency was observed when the

Bu3SnH/AIBN system was used for the chemoselective cascade initiation. We also attempted anionic 6-exo-dig cyclization but found that phenoxide elimination dominates, leading to

17 compounds 5 which can be converted into heterocycle 4, via an anionic 5-endo-dig closure

(Figure 12).

Figure 11. Synthesis of enediyne compounds for model radical cascade reactions.

Figure 12. Optimization of cascade conditions.

Selective radical attack at the alkyl halide in the presence of two alkynes is remarkable

considering that alkynes are also reactive under these conditions.65 Structures of the cascade cyclization products were elucidated by heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond correlation (HMBC) and nuclear Overhauser effect (NOE) NMR experiments. The 2D experiments confirmed that products originate from the 6-exo-dig, 5-exo- dig cascade. Results for the cyclization of the p-methoxy substituted enediyne are discussed in more detail.

No gHMBC correlations for the vinyl C-H and the C3-H at the trisubstituted benzene ring

were observed (Figure 13). The lack of correlation implies that a 5-exo-dig cyclization took

place in the 2nd step giving an exocyclic double bond. The product of an endo-dig cyclization

would be expected to display this gHMBC correlation. All protons of the OMe-substituted rings

were identified by their multiplicity and long range couplings between the two deshielded C(-

OMe) carbons and the respective aromatic meta C-H bonds (H at 7.53 couples to the carbon at

159.7 ppm and H at 7.34 ppm couples to the carbon at 158.6 ppm). One of the two meta C-H

groups (7.53, 130.3 ppm) also displays a HMBC correlation with the vinyl C-H (7.19, 134.1

ppm), which identifies the terminal anisole moiety. The gCOSY spectrum shows hydrogen

correlations in the methoxy-substituted benzene rings and also correlation between the CH2’s of

the –OCH2CH2- moiety.

b) HMBC CHCl3 6 9 11 7 10 1 2 3

e O d g c

f O g

f a b,b' C,H c b' O b C,H C C,H

Vinyl C,H

d a

Figure 13. HSQC and HMBC experiments for the cyclization of p-OMe-substituted enediyne 2d. aTop HSQC NMR highlights select direct C-H couplings. The insert shows all H and C chemical shifts for enediyne 2d. bBottom HMBC NMR shows selected C /H through-bond correlations (colored arrows).

In the tricyclic core, the quaternary carbon (150.8 ppm) ipso to the oxygen of the –

OCH2CH2- moiety shows HMBC couplings with both the aromatic meta C-H (6.92 and 126.5 ppm) and the O-CH2 protons (4.30 and 67.2 ppm). Both the ortho proton at 7.25 ppm and the β-

CH2 group (2.96, 25.3 ppm) correlate with the quaternary aromatic carbon (114.2 ppm) at the

junction of the three cycles (see appendix C for the full list of HMBC correlations), confirming that an initial cyclization followed a 6-exo-dig rather than the 7-endo-dig path. In the latter case,

correlation with the β-protons would not be expected due to the additional bond separating these

atoms. Finally, protons in the CH2 groups remain magnetically equivalent, indicating the absence

of radical closure at the terminal aryl group (in contrast to the cascade transformation of

tetraynes discussed in a subsequent section).

Figure 14. Yields and potential energy surfaces for the cascade cyclization of substituted enediynes (B3LYP/6-31+(d,p), kcal/mol).

As expected from general trends in alkyne cyclizations 59,66 both intramolecular radical

attacks at the triple bonds proceed via an exo-closure leading to the selective formation of

substituted 1-benzylidene-2-phenyl-3,4-dihydro-1H-5-oxa-acenaphthylenes 2. Literature

examples of two consecutive ring closures in bis-TMS-acetylenes67 are scarce. The 87% yield for

the cyclization of bis-TMS-enediyne 2e is a particularly convincing illustration for the efficiency of this radical cascade.

We have explored the cyclization potential energy surfaces for all of the enediynes computationally (Figure 14). Several observations are noteworthy. The activation barrier for the first (6-exo) step is ~5 kcal/mol higher than the barrier for the second (5-exo) ring closure.

Although both cyclization barriers are relatively insensitive to the nature of substituents in the

aromatic ring (0.3-0.6 kcal/mol variations), the sterically demanding TMS group deactivates the

alkyne moiety and increases the activation barriers for both cyclizations by ~2 kcal/mol. Because

this additional barrier does not lead to a lower experimental yield for the cascade transformation

of the TMS-substituted enediyne (in fact, the cascade product yield is the highest for this

substrate!). We conclude that reaction yields reflect the relative selectivity of C-Hal bond

activation vs. attack at a triple bond rather than relative cyclizations rates for the different

substituents. Importantly, both cyclization steps are highly exothermic and irreversible and the

cascade moves down the potential energy slope with each newly formed C-C bond.

Table 1. Computational analysis of enediyne cascade (B3LYP/6-31+ (d, p)), kcal/mol.

R= a) Ph b) p-CH3Ph c) p-FPh d) p-OCH3Ph e) TMS

ΔG‡ 7.9 8.0 7.8 7.7 10.2 6-exo -36.0 -28.1 -35.8 -36.0 -29.9 ΔG1 (68)

ΔG‡ 2.9 2.5 2.6 3.1 4.6 5-exo -30.2 -27.5 -29.6 -29.7 -26.1 ΔG2 (810) -55.3 -55.6 -54.9 -54.8 -41.2b ΔGtotal

2.3 Tetrayne Synthesis and Radical Cascades

Encouraged by these results, we investigated the cascade cyclization of tetra-alkynes 11a-c.

The fully “zipped” cascade product (Figure 16) formed as expected. Although the yield was low

for X=Br (26-35%), the bromide can be quantitatively exchanged to form the iodo tetraalkynes

12a-c, which transform to the fully closed nanoribbons 13a-c in higher yields (52-55% overall,68

~93% per step). This increase again indicates that the reaction yields reflect the chemoselectivity of the first step (intermolecular activation) rather than the efficiency of the cyclizations

(intramolecular propagation). Mass-spectrometry of side products isolated in minor amounts suggests that addition of Bu3Sn moiety to the triple bonds is indeed still a problem.

2D HSQC and HMBC NMR analysis fully confirmed the expected polycyclic skeleton of the two diastereomers of the product (Figure 15 presents the results for this analysis for R=Me, see appendix C for the details). The absence of triple bond carbon resonances confirms that cascade proceeded fully utilizing all alkynes in the process. The presence of diastereotopic CH2 groups confirms the formation of a chirality center in the molecule. Connectivity in the OCH2CH2CH- moiety is supported by the 2D correlations in the gHSQC spectrum in which the two hydrogens at 4.97 and 4.69 ppm are bound to the 65.2 ppm carbon, the two hydrogens at 3.57 and 1.98 ppm to the 30.8 ppm carbon, and the methine proton at 2.03 ppm to the 21.1 ppm carbon. For the bottom part of the ribbon, 2D correlations readily identify all carbons in the free standing and the fused tolyl groups. The CH singlet at 5.28 ppm on the bottom part of the ribbon displays gHMBC correlations with carbons 135.8 in the ipso position of the free tolyl and 129.7 ppm carbon of the isolated CH on the fused tolyl ring. The 5.28 ppm singlet also confirms that the final cyclization and subsequent aromatization took place. Full cascade is also consistent with the presence of only one set of characteristic doublets of a para substituted aromatic rings. Interior

aromatic carbons can be identified by comparing gHMBC with gHSQC. The presence of

gHMBC cross-peaks which are not present in the gHSQC spectrum, indicates the interior

quaternary carbons in the aromatic region. The ortho aromatic C-H in the central ribbon can be

identified due to their significant deshielding (9.08, 128.5 and 8.50, 124.4 on the side with the

fused tolyl ring and 9.02, 128.9 and 7.91, 123.4 on the other side). By identifying these outlying

CH bonds along the perimeter of the structure, one can map the connections of the interior

carbons (Figure 15).

Figure 15. a) HMBC NMR correlations used to establish the structure of cascade product 13a and b) H and C chemical shifts for cascade product 13a.

The proposed cascade mechanism is presented in (Figure 16). Once selective activation of the “weak link” in the presence of four alkynes is accomplished, a cascade of four sequential

exo-dig alkyne cyclizations occurs. Only after all four alkynes are consumed by the radical

cascade does the vinyl radical attack the terminal aryl ring. This attack disrupts aromaticity in

this ring and is only observed when three or more alkynes are present in the starting material

(e.g., this step does not occur in the enediyne cyclizations). We suggest that, for these longer

oligomers, this loss of aromaticity is partially compensated by aromatization in one of the

previously formed rings (i.e., ring 3, Figure 16). The subsequent 1,5 H-shift is also favorable

(ΔG~-34 kcal/mol) because it is assisted by rearomatization (rings 4 and E).69 With each

following step, this molecular system continues thermodynamic descent, resulting in an overall

transformation that is ~ 160 kcal/mol exergonic (Figure 17)!

Figure 16. Synthesis of o-aryleneethynylene tetramers and the proposed mechanism of cascade transformation.

The final H-abstraction step has low stereoselectivity due to the near planarity of the sterically unencumbered radical center. The fully “zipped” ribbon has good solubility in common

organic solvents due to the presence of non-planar parts in the structure. In particular, the

polycyclic core is distorted due to the steric C-H interactions between o-hydrogens in the

peripheral aryl groups.

Figure 17. Relative energies and structures of intermediates for the cascade radical transformation of tetraynes (B3LYP/6-31+G(d,p), kcal/mol). HOMO and LUMO for the final product 13b are given on top.

2.4 Conclusions and Future Work

To a large extent, the highly favorable thermodynamics of the reaction cascade stems from the high energy content of alkyne functional group. This feature has been harnessed before for the preparation of graphene ribbons (Figure 18).

For example, Swager and coworkers utilized electrophile-induced alkyne cyclizations to anneal additional cycles onto a polyphenylene backbone.70 Among the many approaches

developed by Müllen and coworkers for the preparation of polyaromatic scaffolds, the Diels-

Alder polymerization of bis-cyclopentadienones with bis-alkynes incorporates alkyne carbons in

the backbone.71

Expansion of radical cascades described in our work to longer oligoalkynes would

potentially lead to the conceptually different approach toward the preparation of graphene

ribbons. In this approach, the central “polyacetylene” backbone is fully assembled from the

alkyne groups of the starting material via radical polymerization.

Center is assembled via cross-coupling: Alkynes are used to make the side rings Electrophile-induced cyclization Swager

Center is assembled via Diels-Alder reactions: Alkynes are partially incorporated in the center Müllen

O + O

Central rings are assembled via alkyne cyclizations: All central atoms are derived from alkynes

Extension X of the this work

Figure 18. Conceptual approaches for the use of alkyne functionality in preparation of graphene ribbons.

In summary, we have found that selective radical generation from alkyl halides is possible in conjugated oligomeric o-aryleneethynylenes. Subsequent intramolecular transformation proceeds with the yield of >93% per step as a cascade of five fast radical cyclizations followed by aromatization via a 1,5-H shift. This radical cascade may open a new avenue for the preparation of functionalized graphene nanoribbons where, potentially, each of the peripheral

aromatic rings can be unique. Future work includes expansion of this radical cascade towards the

preparation of longer and wider nanoribbons with a variety of functional groups, development of new “weak links” which avoid pentagons in the ribbon, and optimization of conditions for the further aromatization at the peripheral aromatic rings.

CHAPTER THREE

ELECTROPHILE-PROMOTED NUCLEOPHILIC CLOSURE CASCADE REACTIONS OF ALKYNES THROUGH GOLD CATALYSIS

3.1 Introduction

Gold catalysis continues to gain popularity, despite only recently garnering much attention.

It has been ~25 years since the initial breakthroughs of Hutchings and Haruta72 but new Au- catalyzed reactions continue to emerge. As a catalyst, gold provides chemical transformations not yet accomplished by any other metal. 73,74 In the field of homogeneous gold catalysis, the alkyne is one of the most popular substrates. The reason for that popularity is the high reactivity of the alkynes which originates from their electronic structure.75

Alkynes are a unique substrate in that they can act as nucleophiles or electrophiles. On one hand, alkynes possess two orthogonal π-orbitals high in energy occupied by two electrons each.

These react with electrophilic reagents such as halogens in organic synthesis or electrophilic metal centers like gold in the field of transition metal catalysis.76,77 In the interaction with a metal center, both the π-orbital in the plane of metal coordination and the π-orbital perpendicular to it can interact with the d-orbitals of the metal (Figure 19a).

On the other hand, the lowest unoccupied orbital of alkynes is low in energy and thus react with strong nucleophiles like in Reppe’s base-catalysed synthesis of vinyl ethers (Figure 19b).

Figure 19. Alkynes behaving as a) nucleophiles in which they coordinate to metal centers like Au and as b) electrophiles in which the alkyne is attacked from methoxy anion to form methyl vinyl ether.

Weak nucleophiles do not react directly with alkynes, but this is often desired in organic synthesis. However, the alkyne can be activated by coordination to the electrophilic gold complexes as mentioned above. This coordination withdraws electron density from the alkyne and thus makes the alkyne more electrophilic, enabeling the desired attack of weak nucleophiles.

For terminal alkynes A, a second mode of interaction with gold (I)-complexes is known.

The gold replaces the hydrogen atom in the presence of a base and forms gold (I)-alkynyl complexes B. Occasionally both structural motives, the π-coordination and gold-alkynyl-σ-bond like in C can be found in some structures (Figure 20).78,79

Figure 20. Formation of gold (I)-alkynyl complexes B and dual π-coordinated/gold-alkynyl-σ- bond complex C.

The ability to catalyze reactions at low temperatures opens new possibilities for organic synthesis with characteristics not previously encountered with other transition metal catalysts.80

Gold catalysis is a powerful tool for the promotion of cascade reactions because it can

promote nucleophilic reactions through the electrophilic activation of carbon-carbon multiple

bonds.81 Specifically, intra- or intermolecular additions on alkynes, initiated by alkynophilic π- acidic gold catalyst complexes, are important for such strategies. The mechanism of gold catalyzed cyclizations (Figure 21), usually involve nucleophilic groups bearing hydrogen atoms.

The nucleophilic group attacks a coordinated gold-alkyne complex, which then proceeds through a deprotonation-reprotonation sequence that sets free the gold catalyst and the reaction product.82

For cascade processes, once the gold (I) species is regenerated in situ, it coordinates to the next sequential alkyne for additional cyclization till all alkynes are consumed.

Figure 21. The fundamental reactivity pattern in gold catalysis.

3.2 Examples of Gold Catalysis used for Cascade Reactions

Gold catalysis has been utilized to improve upon many existing transformations. For example, the addition of water to alkynes is a synthetic method for the generation of carbonyl compounds. Unlike many other syntheses of carbonyl compounds, the hydration of alkynes is an 31

atom-economical addition without energy-intensive redox chemistry. Since Kucherov’s observation in 1881 that mercury (II) salts catalyze the hydration of alkynes under mild conditions, the reaction has seen many applications in synthesis. The toxicity of mercury compounds and the problems associated with their handling and disposal make the Kucherov reaction unsuitable for modern, sustainable organic synthesis or any large-scale application.

Work by Dixon has demonstrated that these transformations can be achieved more efficiently and environmentally friendly through a gold catalyzed reaction.83 For this particular example, gold(I)-catalyzed cyclization of alkynoic acids were exploited as the first step in a sequence leading to an N-acyl iminium ion cyclization resulting in the formation of complex multi-ring

heterocyclic products of the general structure (Figure 22).

Figure 22. Reaction conditions for gold(I)-catalyzed reaction of alkynoic acids. (a) AuPPh3Cl/AgOTf (1 mol %), toluene, rt, 71%; (b) AuPPh3/AgOTf (1 mol %), toluene, reflux, 68%; (c) AuPPh3Cl/AgOTf (1 mol %), toluene, rt, 3 h then reflux, 2 days, 81%.

It has also been well established that gold catalyzes reactions of alkynes bearing a

proximate oxygen nucleophile. For example, convergent syntheses of α-pyrones have

traditionally involved the lactonization of ketoesters.84 Transition-metal catalyzed

cycloaddition85 and annulation86 reactions are recent alternatives that have attracted much

attention, but most are limited by the poor regioselectivity or the requirement for harsh reaction

conditions. However, the readily accessible propargyl propiolate A could be converted to

different complex α-pyrones B by a gold-catalyzed cascade process with good yields (Figure

23).87

Figure 23. Synthesis of complex α-pyrones by a gold-catalyzed cascade reaction.

Li has also demonstrated a gold (I) catalyzed cascade reaction that forms isochromene heterocycles, which have interesting antibiotic properties.88 This cascade involved an

alkynylation-cyclization of terminal alkynes with ortho-alkynylaryl aldehydes leading to 1-

alkynyl-1H-isochromenes (Figure 24).89

Figure 24. Gold (I) catalyzed alkynylation/cyclization.

The mechanism involves the reaction of terminal alkynes with Me3AuCl in the presence of

a weak base that generates the gold (I) acetylide species A, which then forms the chelate

intermediate B and activates the carbonyl group. The acetylide then reacts with the aldehyde to

give intermediate C followed by attack to the triple bond to give the vinylgold intermediate D.

The carbon-gold bond is then quenched to give the final product E by protonolysis, which in turn regenerates the catalyst (Figure 25).

In a number of examples, nitrogen containing heterocycles are formed through gold (I)- catalyzed process. An efficient protocol was developed by Liu and coworkers for the synthesis of fused heterocyclic multi-ring compounds, pyrrolo[1,2-a]quinolin-1(2H)-ones via a

90 AuBr3/AgSbF6-catalyzed cascade transformation. This strategy affords a straightforward approach to construction of tricyclic lactams in which two new carbon-carbon bonds and one new carbon-nitrogen bond are formed in a one-pot synthetic operation from simple starting material (Figure 26). This intermolecular cascade is unusual because most cascades are intramolecular.91

Figure 25. Mechanism for the gold(I)-catalyzed cascade alkynylation/cyclization.

Figure 26. Synthesis of pyrrolo[1,2-a]quinolin-1(2H)-ones.

The catalytic cycle for this transformation is similar to the gold-catalyzed cascade reactions reported by Li.59,92 For this reaction, the terminal alkyne moiety of the starting material is activated by the AuBr3/AgSbF6 catalyst system to generate intermediate A, which then converts to enamine intermediate B via intramolecular hydroamination. Attack of enamine B by an alkyne

in the presence of AuBr3/AgSbF6 generates a propargylamine C. Finally, the propargylamine is

also activated by a gold-/silver catalyst to generate D, which undergoes intramolecular

hydroarylation to yield the final product E (Figure 27).

B [Au] O N [Au] [Au]

[Au] O NH R1

R1 O NH A O N

R1 [Au] R1 C SM

[Au] O N [Au] R2 O N R1 D R2

R 1 E

Figure 27. Catalytic cycle for the synthesis of pyrrolo[1,2-a]quinolin-1(2H)-ones catalyzed by AuBr3/AgSbF6.

3.3 Examples of Gold Catalyzed Hydroarylation Reactions

If one wishes to design cascade reactions in which a large conjugated carbon containing molecules are formed , one most likely will have to achieve multiple hydroarylation cyclizations.

Hydroarylation is addition in which a hydrogen atom and an aryl group are attached across a double or triple bond. Pd has proven to be a powerful catalyst for these types of reactions, (e.g. 36

the Heck reaction), over the past couple of decades.93,94 The Catellani reaction is another Pd catalyzed reaction based off the Heck reaction which uses norbornene as a template to form complex products with ortho substitution.95 Most hydroarylations of this type involve reactions with alkenes, which is of limited use in the design of highly conjugated PAHs.

As stated above, gold does an excellent job of activating alkynes for addition reactions through a catalytic process. 96 Diynes have attracted gold chemists as well, opening the field for new cascade reactions by initial attack of a nucleophile to the triple bond followed by subsequent reactions with the so-formed reactive intermediates.97

Hashmi and coworkers demonstrated that terminal 1,2-dialkynylarenes undergo an unexpected cyclization / hydroarylation reaction toward naphthalene derivatives through gold (I) catalysis.98 The regioselectivity of the reaction can be controlled by careful catalyst tuning

(Figure 28). Gold plays an important dual role in this reaction, serving to both catalyze the

reaction and activate the substrate by Au-C-σ bond formation.

Figure 28. Intermolecular addition of benzene to 1,2-dialkynylarenes toward naphthalene derivatives.

Much insight went into determining the mechanism of this transformation, as the gold catalyst plays multiple roles in the mechanism. From the many experimental results obtained, the following mechanism emerged as the most plausible (Figure 29). First, the acetylide B is formed

with the help of a basic additive. The dual activated intermediate C then causes a dual role of

gold, where one gold center activates the triple bond as an electrophile by π-coordination and the

gold acetylide reacts as a nucleophile at the β-carbon. Thus, a five-membered ring is formed

producing D. When benzene E is formed, a [1,3]-shift of the proton then provides the gold (I)

carbenoid F. A ring expansion by a [1,2]-shift of the reactive allylic group delivers G.99 After

elimination of [Au]+, the observed arylgold (I) complex100 H is formed, the latter in equilibrium

with the observed digold species I. Finally, a proto-deauration step regenerates the gold (I)

species for additional alkyne activation and delivers the final β-hydroarylation product J.

Figure 29. Mechanistic model to explain the formation of β-phenylnaphthalenes through dual Au activation.

The group of Ohno has also been a strong contributor to the field of gold-catalyzed cascade reactions. They also developed a reaction in which substituted naphthalenes are synthesized from

o-dialkynylbenzene. No dual activation is proposed in this reaction. Instead, regioselective addition of an external nucleophile toward the one terminal alkyne of the starting material and

subsequent 6-endo-dig cyclization into 1,3-disubstituted naphthalenes were proposed.101

Conceptually similar work of Liu and co-workers reported ruthenium-catalyzed naphthalene formation via nucleophilic addition/insertion cascade of dialkynylbenzenes to afford 1,2- disubstituted naphthalene derivatives.102 The nucleophilic addition of external nucleophiles to diynes A bearing internal and terminal alkyne moieties regioselectivly proceeds at the internal alkyne to produce compound B. Ohno’s work uses a similar starting material but, through gold

catalysis, a different regioisomer C is formed (Figure 30).

Figure 30. Synthesis of 1,2 and 1,3 substituted naphthalenes through metal catalyzed hydroarylation reactions.

Although the exact role of the gold catalyst could not be confirmed, it is possible that this reaction also benefits from dual activation of the gold catalyst. The proposed mechanism for this reaction proceeds through a stepwise pathway including intermolecular nucleophilic addition to

A onto terminal alkyne or gold acetylide as depicted in B, protodeauration of C, intramolecular nucleophilic addition of the resulting enol ether/enamine-type intermediate D, and aromatization of E involving protodeauration (1,3-proton shift and /or intermolecular protonation) leading to the naphthalenes F (Figure 31a). To support their catalytic cycle including the formation of

intermediate D, a related silyl enol ether G was prepared and subjected to the cyclization

conditions which gave the corresponding naphthol derivatives Ha and Hb (Figure 31b).

Figure 31. a) Plausible catalytic cycle for the formation of 1,3 disubstituted naphthalenes through gold catalysis. b) Reaction of silyl enol ether G under standard reaction conditions to confirm that the reaction pathway proceeds through intermediate D.

3.4 Synthesis of Polycyclic Aromatic Hydrocarbons through Gold Catalyzed Cascade Reactions Initiated by Hydroamination Cyclizations

Gold-catalyzed inter- or intramolecular hydroamination of alkynes and inter- or

intramolecular hydroarylation of alkynes provide effective avenues for the formation of complex

heterocyclic structures.103 Gold plays a pivotal role in these cascade transformations due to the

ability to promote several types of nucleophilic reactions through electrophilic activation of

carbon-carbon triple bonds and double bonds.104 Ohno and coworkers are the first to devise a

reaction in which extended conjugated carbon systems through gold catalyzed cascade reactions.

These reactions proceed through initial 5-endo-dig hydroaminations105 followed by consecutive

6-endo-dig hydroarylations106 depending on how many o-alkynes are present in the starting

material, yielding fused indole products (Figure 32). Synthesis of other heterocyclic indoles,

such as dihydrobenzoindole, oxepinoindole, and cycloheptaindole derivatives were also

synthesized with this method.107

Figure 32. Synthesis of aryl-annulated fused indoles.

After optimization of the catalytic conditions, the cascade was performed on aniline enediyne starting materials in excellent yields were observed (74-98% except when R was o-

NCC6H4 10%). Substituents included aromatic and aliphatic rings with both donating and accepting substituents on the rings. An additional investigation into the reactivity was achieved by including different arene bridges between the two alkyne systems. These also gave favorable results except for the case in which a pyridine was included in the ring system (15%) (Figure 33).

These were important findings in that these catalytic conditions for this cascade reaction are labile with a number of different functional groups and substituted arene rings which can make products with interesting electronic properties.

Ar XPhosAuCl/AgOTf (5-20 mol %) Ar o N MeCN, 80 C H NH2

N O Ar = 92% 84% 15% 98% F

Figure 33. Effect of various arene tethers on gold catalyzed cascade reaction.

The key to the success of additional hydroarylation steps is the ability to regenerate the catalytic gold (I) species many times throughout the cascade. The proposed mechanism suggests that a weak acid present in the solution is strong enough to regenerate the gold (I) species. The proposed mechanism for the cascade of two alkyne systems is as follows: Initial activation of the

alkyne between two arenes of A by the cationic gold complex (as depicted by B) promotes 5-

endo-dig cyclization to form indolylgold intermediate C. A proto-deauration step then regenerates the gold (I) species and the first cyclization product D. Further activation of the

second alkyne by the gold catalyst to form D leads to a 6-endo-dig cyclization at the C-3 position

of the indole and subsequent rearomatization to give arylgold intermediate E. Finally, proto-

deauration of E produces the fused carbazole F to regenerate the catalyst (Figure 34a). This

mechanism, including cyclization after proto-deauration of the vinyl gold intermediate C, is

supported by a similar reaction with isolated intermediate G. Treatment of G under standard

reaction conditions proceeded to afford the desired carbazole F (Figure 34b).

Figure 34. a) Proposed reaction mechanism for gold catalyzed cascade reaction for the synthesis of fused carbazoles. b) Cyclization of intermediate G using standard reaction conditions.

Additional hydroarylation cyclizations were also able to be achieved by synthesizing extended o-alkyne systems. A hydroamination-double hydroarylation cascade using aniline

derivatives bearing a triyne moiety as the substrate was promoted by a gold(I) catalyst. Similar to

the cascade reaction of enediynes, this produced benzo[a]naphtha[2,1-c] carbazole derivatives in good yields.108 This reaction, like the one with enediynes, is applicable to various substituted

trienyne-type anilines, including 2,3-diethynylthiophene derivatives. The system was able to be

extended to systems with 4 and even 5 alkynes creating compounds with high π conjugation.

These reactions of anilines bearing a tetrayne (Figure 35a) and pentayne (Figure 35b) moiety

allow for the direct construction of highly fused carbazoles. This gold catalyzed cascade process

has produced some of the largest PAHs to date, proving gold catalysis as a viable route for the

synthesis of carbon nanoribbon type structures. In the following chapter, cascades will be

discussed in which fused benzofuran PAHs are synthesized through a similar synthetic route.

Figure 35. a) Tetrayne and b) Pentayne synthesis of fused complex carbazole structures.

CHAPTER FOUR

GOLD CATALYZED CASCADE REACTION OF ENEDIYNES AND TRIYNE FOR THE SYNTHESIS OF FUSED BENZOFURAN POLYCYCLIC AROMATIC HYDROCATBONS

4.1 Introduction

Alkynes are valuable precursors for the preparation of carbon-rich materials109 due to their

high carbon content, modular assembly via reliable cross-coupling chemistry, and propensity for

participating in coordinated and efficient cascade transformations leading to the construction of

polycyclic frameworks.110 Heteroatom incorporation into polycyclic aromatic frameworks fine- tunes their electronic properties, leading to major advances in the field of organic materials.

Annealing of donor heterocycles can expand the utility of carbon rich compounds in materials111,112 and molecular devices.113

As a continuation of our work on alkyne cyclizations,114 we recently reported a cascade transformation of four alkynes into extended polyaromatic structures through a sequence of four exo-dig radical cyclizations.115 The exclusive exo-selectivity in that reaction design relied on the revised rules for alkyne cyclizations116 where, contrary to the original Baldwin rules,117 the preferred approach of a radical or a nucleophile follows the Burgi-Dunitz trajectory.118

4.2 Gold Catalyzed Cascade of Enediynes and Triyne

Guided by the stereoelectronic reasons (“the LUMO-umpolung”) for the switch to endo

selectivity in alkyne cyclizations when alkyne coordinates to an external Lewis Acid

(“electrophile-assisted cyclizations”)51 and intrigued by the expanding list of Au-mediated

45 organic approaches towards polycylic compounds,119 we investigated the feasibility of a sequence which would involve only endo-dig cyclizations by merging three metal-catalyzed steps: 1) Sonogashira cross-coupling, 2) 5-endo-dig cyclization of ortho-alkynyl phenols, and 3)

Au-catalyzed alkyne cyclizations (Figure 36). We also tested whether this cascade can be expanded further via the participation of additional alkynes. These tandem transformations would allow benzofuran fusion to naphthalene, chrysene and related polyaromatic cores.

Tandem of Sonogashira cross-coupling / 5-endo-dig cyclization with a nucleophilic group at the ortho-position (e.g. –OH) has ample literature precedents.120 Our challenge was in extending the cyclization process past the initial 5-endo-dig cyclization toward annealing additional aromatic rings and extending the conjugated framework. In our strategy, we were guided by the work of

Ohno and coworkers, which demonstrated the efficiency of Au-catalyzed hydroamination/ hydroarylation cascades for the preparation of fused indoles and carbazoles.121 Wu et al. has demonstrated the utility of similar cascades mediated by iodine.122 Hashmi used Au(I)-catalysis for the synthesis of naphthalene derivatives from enediynes.123

The library of enediynes was prepared using the differentiated reactivity of the two halogen atoms of 2-bromoiodobenzene in Sonogashira reactions. The aryl iodide was coupled at room temperature under standard Sonogashira conditions using PdCl2(PPh3)2 and CuI in triethylamine whereas subsequent coupling with the less reactive aryl bromide necessitated Pd(PhCN)2Cl2/P(t-

124 Bu)3 as catalyst with the bulky electron rich ligand (Figure 37).

Obtuse trajectory: LUMO of alkyne Y Radical cyclizations (Y=X ) R = allexo R R

Earlier Ref. 9 X

X X

Acute trajectory: "LUMO umpolung" Y M+-assisted cyclizations Y=Nu:

= all endo? Nu E+

Nu Nu Present H+ work + R M R R M+ M

Figure 36. Preferred trajectories for alkyne cyclizations and the possible switch from the “all- exo” radical cascade to the “all-endo” metal-assisted cascade.

Figure 37. Synthesis of enediynes.

Conditions for the cyclization cascades were optimized using 3-((2- ethynylphenyl)ethynyl)thiophene as a model substrate (Table 2). In the presence of Au species, the use of standard Sonogashira solvents (i.e., neat amines) gave low yields of the monocyclized

5-endo product. Use of only two equivalents of base along with o-xylene as a high boiling solvent increased the benzofuran yield to 57%. In the absence of Pd the yields were dramatically decreased (entry 14 and 15).125 Formation of homocoupled products due to the Hay reaction was minimized by utilizing Cu-free conditions. Although addition of Au (I) and Au (III) species decreased the efficiency of benzofuran formation, the addition of Ag salts restored the reactivity.

The 10% ClAuPPh3/AgOTf system provided the first evidence that the full cascade is viable, albeit in a low yield. Better yields of the cascade products 18 were obtained when enediyne, 2-iodophenol, Et3N, and PdCl2(PPh3)2 were allowed to react in o-xylene for one hour at room temperature before the addition of ClAuPPh3/AgOTf and heating in a sealed tube. The various synthesized substituted enediynes were subjected to the optimized conditions in which the full cascade product was observed for most examples albeit in low yields (Table 3). All examples gave a mixture of the monocyclization and the cascade product except for entry 7 in which only the monocyclized product was able to be isolated.

Table 2. Optimization of the catalyst system. a 0.1 M substrate in o-xylene and 2 equiv. of triethylamine were used unless stated otherwise. All reactions were run for 8 hours. b Yields were determined by 1H NMR except for example 9 where the product was isolated. c 1 equiv. of d e Et3N. K2CO3 was used as a base. Reaction was run without PdCl2(PPh3)2.

b entrya catalyst % product: yield

PdCl2(PPh3)2 17a: 57% / 18a: 0% 1 no Au

effect of Au: 2 AuCl 5% 17a: 12% / 18a: 0% 3 AuCl 10% 17a: 20% / 18a: 0% 17a: 19% / 18a: 0% 4 ClAuPPh3 10% 17a: 10% / 18a: 0% 5 AuCl3 10%

effect of Ag: 6 AgOTf 10% 17a: 19% / 18a: 0% 7 AuCl 10% 17a: 13% / 18a: 1% AgBF4 10% 8 AuCl 10% 17a: 32% / 18a: 16% AgOTf 10% 9 ClAuPPh3 10% 17a: 22% / 18a: 12% AgBF4 10% 10 ClAuPPh3 17a: 57% / 18a: 21% AgOTf 10%

effect of base: c 11 ClAuPPh3 10% 17a: 64% / 18a: 11% AgOTf 10% d 12 ClAuPPh3 10% 17a: 0% / 18a: 0% AgOTf 10%

effect of metal: 13 ClAuPPh3 10% 17a: 18% / 18a: 0% AgOTf 10% CuI 5% e 14 ClAuPPh3 10% 17a: 15% / 18a: 0% AgOTf 10% e 15 ClAuPPh3 10% 17a: 5% / 18a: 0%

Table 3. Tandem Sonogashira/cascade of substituted enediynes. aIsolated yield %.

entry enediyne product: yielda

The overall cascade merges the two metal-catalyzed transformations. First, 2-iodophenol

cross-couples with a terminal alkyne via the classic Sonogashira path, followed by 5-endo-dig

attack of oxygen at the activated alkyne. In domino reactions of this nature, a variety of soft

Lewis acidic metals can activate alkynes for an intramolecular nucleophilic attack.126

In the second part of the transformation, gold(I) activates the alkyne towards the 6-endo-dig cyclization where the electron-rich furan moiety serves as a nucleophile (Figure 38). Because the catalytic Au(I) species are regenerated by proto-deauration of the cyclized intermediates, the presence of base in the Sonogashira conditions may be responsible for the relative inefficiency of the full cascade by preventing protodemetallation.127 Alternatively, basic amines may inhibit the

addition step by directly coordinating at gold.128

Figure 38. Au-assisted 6-endo-dig cyclization.

Considering the two possible roles of the basic media, we heated the monocyclized

substituted benzofurans in o-xylene with 10 mol % of ClAuPPh3/AgOTf in the absence of base.

Indeed, all intermediate products were converted into the full cascade product in excellent yields.

In order to extend the Au-catalyzed transformation further, triyne 19 was prepared from enediyne 16c. Reaction of this triyne with 2-iodophenol under the Sonogashira conditions provided only traces of the full cascade product. However, after removal of the base, the 5-endo product underwent clean metal-assisted cascade ring closure induced by ClAuPPh3/AgOTf in o- xylene to form 21. The intermediate products corresponding to monocyclization of the 5-endo product 20 were not observed (Figure 39).

Figure 39. Triyne synthesis and cascade reaction with 2-iodophenol (A) and comparison of “all- exo” and “all-endo” strategies towards the preparation of graphene ribbons (B).

4.3 Conclusions

In conclusion, cross-coupling of 2-iodophenol with a terminal enediyne or triyne sets up an

“all endo” cascade of alkyne cyclizations. The full cascade is more efficient in a two-step procedure which removes base but does not require further purification or isolation. The final

° alkyne cyclizations are promoted by ClAuPPh3/AgOTf system in o-xylene at 150 C. Future

work will optimize reaction conditions for the cyclizations of extended ortho alkyne oligomers in

these domino reactions.

CHAPTER FIVE

FUTURE WORK AND CONCLUSIONS

5.1 Future Work

If ones ultimate goal is to create graphene nanoribbon structures, one must design a system which consists of only six-membered rings. In the earlier chapters, we presented methods to form highly conjugated PAHs through a radical cascade pathway in which all exo cyclizations are achieved (chapter 2), or by a gold catalyzed electrophile-promoted nucleophilic ring closure cascade in which all endo cyclizations are achieved (chapter 4). While both of these processes have proven to be viable methods for synthesizing PAHs, they both contain 5-membered ring formation steps. In the case of the radical cascade, the second cyclization goes through a 5-exo-

dig ring closure due to the design of the starting material. For the gold catalyzed cascade, the

initial cyclization goes through a 5-endo-dig ring closure. In order to achieve all 6-membered

ring formation, the cascade starting material must be redesigned.

In regard to the electrophile-promoted nucleophilic ring closure cascade, after the initial

cyclization, all following steps presented by Ohno and by us go through 6-endo-dig

hydroarylation cyclizations. It was also demonstrated that any isolated intermediates that did not

proceed to completion during the cascade process, could be subject to the standard gold catalytic

conditions to complete the addition cyclizations at near quantitative yields. With those

advantageous results, the future work will develop a gold catalyzed cascade reaction in which all

6-membered rings are formed. We plan to achieve it by initiating the cascade with a 6-endo-dig

hydroarylation by designing a starting material with a biphenyl moiety at the end of the ortho alkyne scaffold (Figure 40).

NH2 R OH R R

OhnoAu/Ag Byers Au/Ag 5-endo 5-endo Au/Ag 6-endo R R HN O

R R [Au] [Au]

N O H

6-endo-dig 6-endo-dig R Hydroarylation Hydroarylation 6-endo-dig [Au] Hydroarylation

R [Au] R [Au] All 6-Membered Rings Formed in Cascade N O H

Figure 40. Comparison of gold catalyzed electrophile-promoted nucleophilic ring closure cascades for the goal of designing an all 6-endo-dig cascade process.

There have been a number of examples of 6-endo-dig hydroarylations presented in the

literature, but no examples have been reported in which this reaction has initiated a cascade

process. Liu has demonstrated the efficiency of this cyclization by performing the discussed 6-

endo hydroarylation reaction on a number compounds in which a sp carbon was being attacked through the use of a ruthenium catalyst.129 Examples of cyclizations at sp2 carbons were also

given but the yields suffered compared to cyclizations at sp carbons. While the cyclization

55 reported did not involve a cascade process, highly conjugated materials such as coronene were synthesized which have potential optoelectric applications.130,131 This cyclization reaction was also efficient in the presence of heterocyclic rings (Figure 41).

Figure 41. Examples of 6-endo hydroarylation reactions through ruthenium catalysis.

Work by Flynn and co-workers also utilized hydroarylation reactions to form complex

structures with a number of functional handles, whereby additional chemistry can be

performed.132 Iodine was used to promote these hydroarylations, and an iodo group was present in the final product. The formation of vinyl iodides in the final product allow for additional coupling reactions to take place to add more complexity and conjugation to the final product

(Figure 42). Due to the precedent discussed above of hydroarylation reactions being able to form complex polycyclic structures and the ability of gold (I) catalysts to promote these reactions, a cascade reaction initiated by a hydroarylation cyclization in which all rings formed throughout the cascade are 6-membered should be attainable (Figure 43).

Figure 42. Iodine promoted hydroarylations for the synthesis of poly-heterocyclic structures.

Figure 43. Gold catalysis promotes 6-endo-dig hydroarylation over 5-exo-dig hydroarylation.

To help promote completion of the cascade shown in Figure 44, donor substituents (e.g.

alkyl, -OMe) should be placed on the biphenyl ring that is involved in the initial cyclization of

the cascade, and accepting substituents (e.g. -CN, -NO2) can be placed on the last ring of the

ortho-alkyne oligomer. Additional electron density in the initiator ring should make this ring a

better nucleophile for cyclization while the accepting groups will help pull the electron density

toward it to help in the complete ”zipping” of the cascade reaction. The electron-rich biphenyl

rings can be synthesized through standard Suzuki coupling methods while the remainder of the

backbone can be synthesized through techniques discussed above which predominantly involves

the use of Sonogashira coupling reactions to add additional alkynes (Figure 44).

D D D

D D

B(OH)2 Sonogashira Suzuki R

Br R

Donor = alkyl, OMe

Acceptor = CN, NO2

Figure 44. Synthesis of starting materials for gold catalyzed hydroarylation cascade incorporating donor and acceptor substituents to promote consumption of all alkynes present.

This method would be advantageous in the synthesis of PAHs and carbon nanoribbons because it produces defect-free graphene substructures. The final product from the hydroarylation can undergo further aromatization through oxidative ring closing reactions such

133 134 as the Scholl or Mallory reactions in which a new C-C bond is formed between adjacent C1 and C6 carbons making a new 6 membered ring. These additional cyclizations will help to planarize the nanoribbon structure which will in turn be beneficial in the π-overlap and electron transport across the surface (Figure 45). Incorporation of accepting and donating substituents on opposite sides of the PAH framework would allow for a new design of nano-scale semiconductors and charge transport devices. There are many more exciting possibilities that are dependent on the success of this project.

Figure 45. Synthesis of PAH and carbon nanoribbons through gold catalyzed hydroarylation cascade and Scholl or Mallory oxidative ring closing reactions.

5.2 Conclusions

This dissertation provides two new synthetic routes for the synthesis of polycyclic aromatic

hydrocarbons and carbon nanoribbons. The first, utilizes a novel radical cascade process,

allowing for the synthesis of complex, polycyclic systems. The radical conditions for this

reaction allow the presence of a number of donating and accepting functional groups, which are

orthogonal to the radical cascade that takes place. It is useful to have a process such as this, as

these functional groups allow for the formation of molecules that have gained much interest in

the budding field of organic nano-electronics, such as charge transfer devices, transistors,

photovoltaic devices, rectifiers, and semiconductors. Future work for the radical cascade process

is focused toward extending the cascade reaction in order to synthesize larger conjugated

materials.

A gold catalyzed electrophile-promoted nucleophilic ring closure cascade was also developed in which functionalized fused benzofuran structures were synthesized. While the mechanism of this cascade differs greatly from the radical cascade process, both systems achieve the same goal; the synthesis of functionalized PAHs and carbon nanoribbons. As discussed above, this project aims to extend the cascade process as well as form conjugated systems consisting of all 6-membered rings, as the ultimate goal is to try and mimic a pristine carbon nanoribbon structure. The future work in this project aims to achieve that goal through a gold catalyzed, hydroarylation cascade reaction. These two processes have helped establish new precedent in the field of organic materials research and will hopefully aid those also searching for efficient synthetic avenues for the formation of these interesting graphene substructures.

APPENDIX A

EXPERIMENTAL DETAILS FOR RADICAL CASCADE (CH. 2)

Synthesis

THF and hexanes used for reactions were dried over sodium and distilled. Hexanes used for column chromatography were distilled prior to use. All other solvents were used as purchased. Column Chromatography was performed using silica gel (60 Å). Unless otherwise noted, all 1H NMRs were run on 400 MHz and 600 MHz spectrometer in CDCl3 and CD3CN and all 13C NMR were run on 100 MHz and 150 MHz spectrometer in CDCl3 and CD3CN. Proton chemical shifts are given relative to the residual proton signals of the deuterated solvent CDCl3 (7.26 ppm), CD3CN (1.94 ppm). Carbon chemical shifts were internally referenced to the deuterated solvent signals in CDCl3 (77.00 ppm), CD3CN (1.4, 118.7). All J-coupling values are reported in Hertz (Hz).

General Procedure for protection of 2,3 iodophenol with “weak link” group (a): A suspension of 2,3 iodophenol (0.77 mmol), K2CO3 (1.69 mmol) and 18-crown-6 (0.04 mmol) in 18 mL of acetone was brought to reflux. Through top of condenser 1,2 dibromoethane (3.06 mmol) was added drop wise. Reaction was monitored by TLC. At completion of reaction, usual aqueous workup was performed. The reaction mixture was purified by flash chromatography on silica gel, (eluent: hexane/EtOAc) on silica gel to afford compound a.

Procedure for synthesis of 3-iodophenyl diethylcarbamate (b) : To a stirred suspension of NaH (1.09 g, 45.47 mmol), in THF (23 mL), a solution of 3- iodophenol (5.00 g, 22.73 mmol), in THF (5.70 mL) was drop wise added at room temperature. After stirring the reaction mixture for 2 h. N,N-diethylcarbamoyl chloride (6.17 g, 45.47 mmol) in THF (8 mL) was added. Stirring was continued for another 8 h. Usual aqueous work up gave the crude carbamate which was purified by column chromatography (eluent: hexane/EtOAc) on silica gel to afford compound b.

Procedure for synthesis of 2,3-diiodophenyl diethylcarbamate (c) : n-BuLi (14.95 mL of a 1.6M sol. in hexane, 23.91 mmol) was added to solution of i-Pr2NH (3.38 mL, 23.91 mmol) in THF (50 mL) at 0o C. After 30 min at 0o C the LDA solution was cooled to -78o C and the c (21.74 mmol) was added. The resulting solution was stirred for 30 min at -78o C and then iodine (6.62 g, 26.09 mmol) in THF (15 mL) was added. After 30 min at low temperature the reaction mixture was allowed to warm to room temperature, H2O was added and THF evaporated under reduced pressure. The aqueous phase was extracted with EtOAc (3 x 25 mL) and the combined organic layers were washed with 1M HCl, dried over anhydrous Na2SO4, and evaporated under reduced pressure. The crude mixture was purified by column chromatography (eluent: hexane/EtOAc) on silica gel to afford compound c.

Procedure for synthesis of 2,3-diiodophenol (d) : To a solution of the carbamate 3 (10.07 mmol) in EtOH (130 mL) a large excess of NaOH (4.03 g, 0.10 mol) was added. The mixture was refluxed for 5-8 h. After cooling to room temperature most of the EtOH was evaporated under reduced pressure, the residue was diluted with diethyl ether and the excess of NaOH was neutralized at 0o C using a 1M solution of HCL. The aqueous solution was extracted with diethyl ether (3 x 20 mL) and the combined organic phase was washed with brine, dried with Na2SO4, and evaporated under reduced pressure. The crude was purified by column chromatography (eluent: hexane/EtOAc) on silica gel to afford compound d.

General Procedure for Sonogashira cross coupling of 6 with different substituted acetylenes (1): A suspension of aryl dihalide (0.59 mmol), PdCl2 (PPh3)2 (29.70 µmol), Cu(I) iodide (29.70 µmol) in 15 mL of triethylamine was degassed three times with freeze/pump/thaw technique in a flame dried round bottom flask. 2.5 equiv. of 4-ethynyl-anisole (1.49 mmol) was added using a syringe once solution thawed and allowed to react for 8 hours. The reaction was monitored by TLC. After total consumption of the aryl halide, the reaction mixture was filtered through celite and washed with methylene chloride (3 × 30 mL). The organic layer was washed with a saturated solution of ammonium chloride (2 × 30 mL), water (2 × 30 mL) and dried over anhydrous Na2SO4. Solvent was removed in vacuo. The reaction mixture was purified by flash chromatography on silica gel, (eluent: hexane/EtOAc) on silica gel to afford compound 1.

General Procedure for radical cascade of (2): To three separate round-bottom flasks were added 40.00 mg of bis-methylbenzene (1) in 6mL of benzene, 59.70 mg Bu3SnH in 2 mL of benzene, and 1.53 mg AIBN in 2 mL benzene. Nitrogen was bubbled in flasks for 20 min to degas solution. Bu3SnH and AIBN were added by syringe pump through the top of a condenser over the course of 6 hours to a refluxing solution of bis- methylbenzene. The reaction was monitored by TLC. After conversion of all starting material, the reaction mixture was concentrated and purified by preparatory TLC, (eluent: hexane/EtOAc) on silica gel to afford compound 2.

General Procedure for Finkelstein reaction of (3) and (13): Sodium iodide was added in one portion in to a stirred solution of (1c)(55 mg, 0.13 mmol) in 10 mL of acetone. The mixture was heated to 50° C under nitrogen atmosphere for 8 h. Upon completion then solvent was removed under vacuum. The resulting solid was dissolved in CH2Cl2 and washed with saturated Na2S2O3, water, brine and dried over anhydrous Na2SO4. Solvent was removed in vacuo giving compound (3) in quantitative yield as a light yellow oil.

Procedure for anionic cascade reaction (4) and (5): A 0.1 M solution of (3) (61 mg, 0.17 mmol) in 15 mL 3:2 hexane/Et2O was deoxygenated by bubbling N2 for 5 minutes. The mixture was cooled to -78° C. A solution of n-BuLi (0.16 mL of a 1.6 M sol. in hexane, 0.25 mmol) was added drop wise. The solution was stirred for 10 more minutes at -78° C and then the cooling bath was removed. The reaction mixture was stirred 2.5 h at room temp in order for the cyclization to occur. The cyclized solution was cooled back down to -78° C and an excess of MeOH (30.5 µL, 0.77 mmol) was added. After the addition the cooling bath was removed and the reaction was stirred for 3 h. To the reaction mixture was added deionized water. The mixture was extracted with CH2Cl2 and washed with ammonium

chloride and brine solution 2 times and dried over Na2SO4. Solvent was removed in vacuo and purified by flash chromatography on silica gel, (eluent: hexane/EtOAc) on silica gel to afford compounds (4) and (5).

Procedure for deprotection of TMS protecting groups (2f): To a solution of ((3-(2-bromoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis(trimethylsilane) 6e (225 mg, 0.57 mmol), in 1:1 mixture of MeOH/THF (18 mL) was added K2CO3 (30 mg, 0.21 mmol). The solution was stirred at room temperature for 8 h under nitrogen. Water was added to quench the reaction and usual aqueous work up was performed. The reaction mixture was purified by flash chromatography on silica gel, (eluent: hexane/EtOAc) on silica gel to afford compound 2f.

1-(2-bromoethoxy)-2,3-diiodobenzene (a):

Br Chromatographic purification (10% ethyl acetate in hexanes) afforded compound a O 1 (77%) as a white solid. Rf=0.6 (20% ethyl acetate in hexanes); H NMR (400 MHz, I CDCl3): δ 7.52 (dd, J= 1.1, 7.9 Hz, 1H), 7.02 (t, J= 8.0 Hz, 1H), 6.70 (dd, J= 3.0, 13 I 0.8 Hz, 1H), 4.28 (t, J= 6.3 Hz, 2H), 3.67 (t, J= 6.3 Hz, 2H) ; C NMR (150 MHz, CDCl3): δ 158.1, 132.6, 130.5, 111.2, 110.0, 101.5, 69.7, 28.3; HRMS (EI): calcd for C8H7OBrI2 [M]+ 451.7770, found 451.7760.

((3-(2-bromoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))dibenzene (1a):

O Chromatographic purification (10% ethyl acetate in hexanes) afforded compound 1a (72%) as a light yellow oil. Rf=0.5 (10% ethyl acetate in 1 hexanes); H NMR (600 MHz, CDCl3): δ 7.64 (d, J= 6.5 Hz, 2H), 7.61 (dd, J= 5.7, 2.3 Hz, 2H), 7.37 (m, 6H), 7.24 (s, 1H), 7.23 (d, J= 2.0 Hz, 1H), 6.86 (t, J= 4.6 Hz, 1H), 4.38 (t, J= 6.2, 2H), 3.71 (t, J= 6.3, 2H) ; 13C NMR (150 MHz, CDCl3): δ 158.6, 131.6, 131.6, 131.5, 128.8, 128.4, 128.3, 128.3, 127.4, 125.0, 123.6, 123.1, 116.2, 112.9, 98.3, 93.8, 88.1, 84.4, 69.0, 28.9; HRMS (EI): calcd for C24H17OBr [M]+ 400.04628, found 400.04552.

4,4'-((3-(2-bromoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis(methylbenzene) (1b):

O Chromatographic purification (10% ethyl acetate in hexanes) afforded compound 1b (83%) as a light yellow oil. Rf=0.5 (10% ethyl acetate in 1 hexanes); H NMR (600 MHz, CDCl3): δ 7.49 (dd, J= 12.8, 8.0 Hz, 4H), 7.22 (d, J= 3.8 Hz, 1H), 7.21 (s, 1H), 7.16 (dt, J= 7.93, 0.7 Hz, 4H), 6.86 (dd, J= 6.5, 2.8 Hz, 1H), 4.39 (t, J= 6.4 Hz, 2H), 3.72 (t, J= 6.4 Hz, 2H), 2.38 (s, 13 6H) ; C NMR (150 MHz, CDCl3): δ 158.6, 138.6, 138.4, 131.6, 131.5, 129.1, 129.1, 128.6, 127.6, 125.1, 120.6, 120.2, 116.5, 113.0, 98.5, 94.0, 87.6, 83.8, 69.1, 28.8, 21.5; HRMS (EI): calcd for C26H21OBr [M]+ 428.07758, found 428.07769.

4,4'-((3-(2-bromoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis(fluorobenzene) (1c):

Br F

O Chromatographic purification (15% ethyl acetate in hexanes) afforded compound 1c (87%) as a light red oil. Rf=0.4 (10% ethyl acetate in 1 hexanes); H NMR (600 MHz, CDCl3): δ 7.55 (m, 4H), 7.24 (t, J= 8.0 Hz, 1H), 7.20 (dd, J= 7.7, 1.1 Hz, 1H), 7.05 (td, J= 8.7, 1.6 Hz, 4H), 6.87 (dd, J= 13 F 8.1, 1.1 Hz, 1H), 4.39 (t, J=6.3 Hz, 2H), 3.72 (t, J= 6.3 Hz, 2H) ; C NMR (150 MHz, CDCl3): δ 163.4 (d, J= 13.1 Hz), 161.8 (d, J= 13.1 Hz), 158.6, 133.54, 133.48, 133.47, 133.41, 128.9, 127.2, 125.0, 119.7 (d, J= 3.5 Hz), 119.3 (d, J= 3.3 Hz), 116.0, 112.9, 97.1, 92.7, 87.7, 84.1, 68.9, 28.8; HRMS (EI): calcd for C24H15OBrF2 [M]+ 436.02744, found 436.02660.

4,4'-((3-(2-bromoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis(methoxybenzene) (1d):

Br O O Chromatographic purification (10% ethyl acetate in hexanes) afforded 1 compound 1d (74%) as a red oil. Rf=0.5 (10% ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 7.53 (dd, J= 14.3, 8.9 Hz, 4H), 7.20 (d, J= 2.9 Hz, 1H), 7.19 (s, 1H), 6.88 (d, J= 8.5 Hz, 4H), 6.84 (dd, J= 6.1, 3.2 Hz, 1H), 4.38 O (t, J= 6.4 Hz, 2H), 3.83 (s, 6H), 3.71 (t, J= 6.4 Hz, 2H) ; 13C NMR (150 MHz, CDCl3): δ 159.8, 159.7, 158.4, 133.13, 133.06, 128.4, 127.5, 125.0, 116.5, 115.8, 115.4, 114.0, 113.98, 112.8, 98.3, 93.8, 87.0, 83.2, 69.1, 55.3, 28.9; HRMS (EI): calcd for C26H21O3Br [M]+ 460.06741, found 460.06803.

((3-(2-bromoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis(trimethylsilane) (1e):

Br O Si Chromatographic purification (10% ethyl acetate in hexanes) afforded compound 1 1e (83%) as a tan oil. Rf=0.5 (15% ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 7.16 (t, J= 8.0 Hz, 1H), 7.11 (dd, J= 7.7, 1.0 Hz, 1H), 6.8 (dd, J= 8.2, Si 0.9 Hz, 1H), 4.31 (t, J= 6.5 Hz, 2H), 3.64 (t, J= 6.4 Hz, 2H), 0.28 (s, 9H), 0.27 (s, 13 9H) ; C NMR (150 MHz, CDCl3): δ 159.2, 128.9, 127.5, 125.7, 116.5, 113.7, 103.8, 102.9, 98.8, 69.2, 28.6, 0.05, 0.02; HRMS (EI): calcd for C18H25OBrSi2 [M]+ 392.06274, found 392.06123.

1-(2-bromoethoxy)-2,3-diethynylbenzene (1f)

Br Chromatographic purification (5% ethyl acetate in hexanes) afforded compound 1f 1 O (94%) as a brown solid. Rf=0.6 (10% ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 7.23 (t, J= 8.0 Hz, 1H), 7.15 (d, J= 7.7 Hz, 1H), 6.87 (d, J= 8.3 Hz, 1H), 4.33 (t, J= 6.6 Hz, 2H), 3.56 (s, 1H), 3.34 (s, 1H) ; 13C NMR (150 MHz, CDCl3): δ 159.4, 129.5, 127.1, 125.9, 115.5, 113.5, 86.0, 81.7, 81.6, 77.8, 69.1, 28.5; HRMS (EI): calcd for C12H9OBr [M]+ 247.9837, found 247.9838.

1,1'-((3-(2-bromoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))dinaphthalene (1g)

Br Chromatographic purification (10% ethyl acetate in hexanes) afforded compound O 1 1g (88%) as a light brown oil. Rf=0.4 (15% ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.68 (dd, J= 8.4, 0.7 Hz, 1H), 8.59 (dd, J= 8.4, 0.7 Hz, 1H), 7.86 (m, 5H), 7.79 (dd, J= 7.1, 1.1 Hz, 1H), 7.47 (m, 2H), 7.44 (m, 1H), 7.40 (m, 2H), 7.33 (t, J= 16.0 Hz, 1H), 7.23 (m, 2H), 6.94 (d, J= 8.2 Hz, 1H), 13 4.47 (t, J= 6.2 Hz, 2H), 3.80 (t, J= 6.3 Hz, 2H) ; C NMR (150 MHz, CDCl3): δ 158.9, 133.4, 133.3, 133.14, 133.11, 130.9, 130.8, 128.9, 128.8, 128.1, 128.0, 127.4, 127.0, 126.8, 126.7, 126.6, 126.4, 126.3, 125.4, 125.18, 125.17, 121.2, 120.8, 116.1, 112.4, 96.6, 93.0, 92.0, 89.4, 69.0, 28.8; HRMS (EI): calcd for C32H21OBr [M]+ 500.07758, found 500.07750.

4,4'-((3-(2-iodoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis(fluorobenzene) (3)

I F O Washes with Na2S2O3, water, brine afforded the compound 3 (>99%) as a light 1 yellow oil. Rf=0.5; H NMR (600 MHz, CDCl3): δ 7.57 (m, 2H), 7.53 (m, 2H), 7.23 (t, J= 8.0 Hz, 1H), 7.19 (dd, J= 2.9, 1.1 Hz, 1H), 7.05 (t, J= 8.6 Hz, 4H), 6.85 (dd, J= 3.0, 0.9 Hz, 1H), 4.34 (t, J= 13.6 Hz, 2H), 3.50 (t, J= 13.6 Hz, 2H) F 13 ; C NMR (150 MHz, CDCl3): δ 163.4 (d, J= 13.2 Hz), 161.8 (d, J= 13.2 Hz), 158.4, 133.5 (d, J= 6.8 Hz), 133.4 (d, J= 6.7 Hz), 128.9, 127.2, 124.9, 119.7 (d, J= 3.2 Hz), 119.2 (d, J= 3.3 Hz), 115.9, 115.7 (d, J= 22.2 Hz), 115.6 (d, J= 22.0 Hz), 112.7, 97.1, 92.7, 87.7, 84.1, 69.6, 0.8; HRMS (EI): calcd for C24H15F2OI [M]+ 484.0136, found 484.0133.

2,2'-((3-(2-bromoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis((p-tolylethynyl)benzene) (11a)

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 1 Br 11a (84%) as a oil. Rf=0.2 (15% ethyl acetate in hexanes); H NMR (600 MHz, O CD3CN): δ 7.56 (d, J= 0.8 Hz, 1H), 7.54 (d, J= 1.4 Hz, 1H), 7.46 (m, 2H), 7.36 (dd, J= 8.0, 4.7 Hz, 2H), 7.33 (td, J= 15.3, 9.5 Hz, 2H), 7.30 (m, 1H), 7.29 (m, 2H), 7.28 (m, 1H), 7.25 (m, 1H), 7.21 (td, J= 15.3, 7.6 Hz, 1H), 7.12 (d, J= 7.9 Hz, 2H), 7.05 (d, J= 7.9 Hz, 2H), 7.02 (dd, J= 8.4, 0.9 Hz, 1H), 4.32 (t, J= 5.9 Hz, 2H), 13 3.53 (t, J= 5.9 Hz, 2H), 2.29 (s, 3H), 2.25 (s, 3H) ; C NMR (150 MHz, CD3CN): δ 160.2, 140.2, 140.0, 133.4, 133.2, 132.8, 132.6, 132.5, 132.4, 130.9, 130.3, 130.2, 129.7, 129.6, 129.2, 129.16, 128.0, 126.6, 126.57, 126.3, 126.1, 126.05, 120.8, 120.76, 116.2, 114.7, 97.8, 94.8, 94.7, 93.5, 92.8, 89.3, 88.5, 88.4, 70.2, 30.6, 21.64, 21.6; HRMS (EI): calcd for C42H29BrO [M]+ 628.14018, found 628.14014.

2,2'-((3-(2-iodoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis((p-tolylethynyl)benzene) (12a)

Chromatographic purification (15% ethyl acetate in hexanes) afforded compound 1 12a (99%) as a oil. Rf=0.3 (15% ethyl acetate in hexanes); H NMR (600 MHz, I O CDCl3): δ 7.63 (d, J= 7.5 Hz, 1H), 7.55 (d, J= 7.6 Hz, 1H), 7.52 (d, J= 7.6 Hz, 1H), 7.50 (d, J= 7.7 Hz, 1H), 7.43 (d, J= 7.9 Hz, 2H), 7.40 (d, J= 7.9 Hz, 2H), 7.28 (t, J= 7.3 Hz, 2H), 7.24 (m, 3H), 7.19 (t, J= 7.5 Hz, 1H), 7.12 (d, J= 7.9 Hz, 2H), 7.08 (d, J= 7.9 Hz, 2H), 6.89 (d, J= 8.2 Hz, 1H), 4.22 (t, J= 7.5 Hz, 2H), 3.18 (t, 13 J= 7.5 Hz, 2H), 2.35 (s, 3H), 2.33 (s, 3H) ; C NMR (150 MHz, CDCl3): δ 158.7, 138.4, 132.5, 132.3, 131.7, 131.6, 131.5, 129.0, 128.95, 128.9, 128.0, 127.9, 127.6, 126.1, 126.0, 125.6, 125.59, 125.5, 120.2, 116.3, 113.5, 97.2, 93.9, 93.7, 92.9, 92.0, 88.2, 87.8, 87.7, 70.2, 21.5, 21.49, 0.6; HRMS (EI): calcd for C42H29IO [M]+ 676.12631, found 676.12625.

2,2'-((3-(2-bromoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis((phenylethynyl)benzene) (11b)

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 1 11b (84%) as a orange oil. Rf=0.2 (15% ethyl acetate in hexanes); H NMR (700 Br O MHz, CDCl3): δ 7.62 (d, J= 7.6 Hz, 1H), 7.54 (m, 4H), 7.50 (m, 3H), 7.31 (m, 3H), 7.29 (m, 2H), 7.25 (m, 6H), 7.19 (t, J= 7.6 Hz, 1H), 6.91 (d, J= 8.2 Hz, 1H), 13 4.28 (t, J= 6.8 Hz, 2H), 3.41 (t, J= 6.9 Hz, 2H) ; C NMR (100 MHz, CDCl3): δ 158.9, 132.5, 132.3, 131.8, 131.75, 131.64, 131.6, 129.0, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.75, 126.1, 125.7, 125.6, 125.4, 123.23, 123.2, 113.7, 97.1, 93.6, 93.4, 92.8, 92.0, 88.4, 88.3, 88.2, 69.3, 28.4; HRMS (EI): calcd for C40H25OBr [M]+ 600.1089, found 600.1088.

2,2'-((3-(2-iodoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis((phenylethynyl)benzene) (12b)

Chromatographic purification (20% ethyl acetate in hexanes) afforded 1 compound 12b (99%) as a orange oil. Rf=0.2 (15% ethyl acetate in hexanes); H I O NMR (400 MHz, CDCl3): δ 7.62 (d, J= 7.4 Hz, 1H), 7.53 (m, 5H), 7.50 (m, 2H), 7.27 (m, 11H), 7.19 (t, J= 6.7 Hz, 1H), 6.89 (d, J= 8.1 Hz, 1H), 4.23 (t, J= 7.4 13 Hz, 2H), 3.20 (t, J= 7.4 Hz, 2H) ; C NMR (100 MHz, CDCl3): δ 158.6, 132.5, 132.3, 131.8, 131.64, 131.6, 129.0, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 126.1, 125.7, 125.6, 125.5, 125.4, 123.2, 116.2, 113.4, 97.0, 93.6, 93.4, 92.8, 92.0, 90.8, 88.4, 88.3, 70.1, 0.6; HRMS (EI): calcd for C40H25IO [M]+ 648.53037, found 648.5357.

2,2'-((3-(2-bromoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis(((4- methoxyphenyl)ethynyl)benzene) (11c)

O Chromatographic purification (25% ethyl acetate in hexanes) afforded compound 11c (82%) as an orange-red oil. Rf=0.1 (15% ethyl acetate in 1 Br hexanes); H NMR (600 MHz, CDCl3): 7.64 (d, J= 7.5 Hz, 1H), 7.56 (d, J= O δ 7.7 Hz, 1H), 7.53 (d, J= 7.7 Hz, 1H), 7.49 (d, J= 8.5 Hz, 3H), 7.46 (d, J= 8.6 Hz, 2H), 7.31 (d, J= 7.7 Hz, 1H), 7.25 (m, 4H), 7.18 (t, J= 7.6 Hz, 1H), 6.91 (d, J= 8.2 Hz, 1H), 6.83 (d, J= 8.6 Hz, 2H), 6.79 (d, J= 8.6 Hz, 2H), 4.29 (t, J= 6.8 Hz, 2H), 3.78 (s, 3H), 3.76 (s, 3H), 3.44 (t, J= 6.8 Hz, 2H); 13C NMR (150 MHz, CDCl3): 159.6, 159.5, 158.8, 133.3, 133.2, 133.1, 132.5, 132.2, 131.5, O δ 131.3, 128.9, 128.0, 127.9, 127.7, 127.4, 126.0, 125.8, 125.6, 125.5, 125.3, 116.3, 115.3, 113.9, 113.8, 113.76, 113.7, 97.2, 93.8, 93.5, 92.9, 91.9, 88.0, 87.2, 87.1, 69.3, 55.15, 55.1, 28.5; HRMS (ESI): calcd for C42H29BrO3 [M]+ 683.11978, found 683.12098.

2,2'-((3-(2-iodoethoxy)-1,2-phenylene)bis(ethyne-2,1-diyl))bis(((4- methoxyphenyl)ethynyl)benzene) (12c)

O Chromatographic purification (25% ethyl acetate in hexanes) afforded compound 12c (99%) as an orange-red oil. Rf=0.1 (15% ethyl acetate in 1 hexanes); H NMR (600 MHz, CDCl3): δ 7.63 (d, J= 7.6 Hz, 1H), 7.55 (d, J= I O 7.7 Hz, 1H), 7.51 (d, J= 7.7 Hz, 1H), 7.48 (m, 3H), 7.45 (d, J= 8.8 Hz, 2H), 7.29 (t, J= 7.6 Hz, 1H), 7.24 (m, 4H), 7.18 (t, J= 3.2 Hz, 1H), 6.89 (d, J= 8.2 Hz, 1H), 6.83 (d, J= 8.7 Hz, 2H), 6.80 (d, J= 8.6 Hz, 2H), 4.24 (t, J= 7.4 Hz, 2H), 3.79 (s, 3H), 3.78 (s, 3H), 3.22 (t, J= 7.4 Hz, 2H); 13C NMR (150 MHz, CDCl3): δ 159.6, 159.55, 158.6, 133.2, 133.1, 132.5, 132.3, 131.5, 131.4, 128.9, O 128.0, 127.9, 127.8, 127.4, 126.1, 125.8, 125.7, 125.5, 125.4, 116.2, 115.4, 115.36, 113.9, 113.83, 113.8, 113.5, 97.2, 93.8, 93.5, 92.9, 91.9, 88.1, 87.2, 87.1, 70.2, 55.2, 0.6; HRMS (ESI): calcd for C42H29IO3 [M]+ 709.12396, found 709.12371.

(E)-5-benzylidene-4-phenyl-3,5-dihydro-2H-cyclopenta[de]chromene (2a)

O Chromatographic purification (15% ethyl acetate in hexanes) afforded compound 1 2a (63%) as a yellow oil. Rf=0.3 (15% ethyl acetate in hexanes); H NMR (700 MHz, CDCl3): δ 7.54 (d, J= 3.9 Hz, 2H), 7.46 (m, 5H), 7.40 (m, 1H), 7.36 (tt, J= 9.9, 1.5 Hz, 1H), 7.28 (s, 1H), 7.02 (m, 1H), 7.00 (d, J= 7.5 Hz, 1H), 6.88 (t, J= 7.8 Hz, 1H), 6.72 (d, J= 8.0 Hz, 1H), 4.24 (t, J= 5.7 Hz, 2H), 2.92 (t, J= 5.7 Hz, 2H) ; 13C NMR (150 MHz, CDCl3): δ 151.0, 141.7, 137.0, 134.8, 134.1, 134.0, 133.0, 131.6, 130.4, 130.2, 129.9, 129.4, 128.4, 128.3, 128.2, 126.9, 116.6, 114.6, 67.1, 25.3 ; UV/Vis (MeOH): max = 273 nm; HRMS (EI): calcd for C24H18O [M]+ 322.1358, found 322.1349.

(E)-5-(4-methylbenzylidene)-4-(p-tolyl)-3,5-dihydro-2H-cyclopenta[de]chromene (2b)

O Chromatographic purification (15% ethyl acetate in hexanes) afforded compound 1 2b (70%) as a yellow oil. Rf=0.3 (15% ethyl acetate in hexanes); H NMR (600 MHz, CD3CN): δ 7.46 (d, J= 7.6 Hz, 2H), 7.34 (d, J= 7.6 Hz, 2H), 7.30 (d, J= 7.6 Hz, 2H), 7.27 (d, J= 7.6 Hz, 2H), 7.24 (s, 1H), 7.08 (d, J= 7.6 Hz, 1H), 6.90 (t, J= 7.7 Hz, 1H), 6.72 (d, J= 8.0 Hz, 1H), 4.26 (t, J= 5.6 Hz, 2H), 2.93 (t, J= 5.7 Hz, 2H), 2.40 (s, 6H) 13 ; C NMR (150 MHz, CD3CN): δ 152.5, 142.4, 140.0, 138.2, 135.7, 135.4, 135.3, 134.2, 133.0, 132.7, 131.4, 130.8, 130.49, 130.47, 128.1, 117.6, 115.6, 68.4, 26.3, 21.8, 21.7 ; UV/Vis (MeOH): max = 274 nm; HRMS (EI): calcd for C26H22O [M]+ 350.16707, found 350.16618.

(E)-5-(4-fluorobenzylidene)-4-(4-fluorophenyl)-3,5-dihydro-2H-cyclopenta[de]chromene (2c)

F Chromatographic purification (15% ethyl acetate in hexanes) afforded compound 1 2c (87%) as a red oil. Rf=0.4 (15% ethyl acetate in hexanes); H NMR (600 MHz, CD3CN): δ 7.55 (dd, J= 8.5, 5.6 Hz, 2H), 7.43 (dd, J= 8.5, 5.7 Hz, 2H),

F 7.20 (q, J= 8.9 Hz, 3H), 7.17 (d, J= 4.8 Hz, 1H), 6.99 (d, J= 7.5 Hz, 1H), 6.90 (t, J= 7.8 Hz, 1H), 6.73 (d, J= 8.1 Hz, 1H), 4.24 (t, J= 5.8 Hz, 2H), 2.89 (t, J= 5.8 Hz, 2H) ; 13C NMR (150 MHz, CD3CN): δ 164.1 (d, J= 107.5 Hz), 162.5 (d, J= 105.6 Hz), 152.3, 142.7, 134.9, 134.1 (d, J= 3.27 Hz), 133.9, 133.4, 132.9 (d, J= 72.6 Hz), 132.7 (d, J= 72.6 Hz), 132.6, 131.8 (d, J= 3.3 Hz), 130.8, 128.2, 117.23, 116.5, 116.4 (d, J= 4.2 Hz), 116.2, 115.7, 68.0, 25.8 ; UV/Vis (MeOH): max = 301 nm; HRMS (EI): calcd for C24H16OF2 [M]+ 358.11693, found 358.11632.

(E)-5-(4-methoxybenzylidene)-4-(4-methoxyphenyl)-3,5-dihydro-2H- cyclopenta[de]chromene (2d)

O Chromatographic purification (15% ethyl acetate in hexanes) afforded 1 compound 2d (74%) as a red oil. Rf=0.4 (20% ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 7.53 (d, J= 8.0 Hz, 2H), 7.34 (d, J= 4.1 Hz, 2H), O 7.25 (t, J= 5.3 Hz, 1H), 7.19 (s, 1H), 7.00 (d, 4.1 Hz, 2H), 6.96 (d, 4.1 Hz, 2H), 6.92 (t, 5.7 Hz, 1H), 6.76 (d, 8.0 Hz, 1H), 4.30 (t, 5.6 Hz, 2H), 3.88 (s, 3H), 3.87 13 (s, 3H), 2.96 (t, 5.6 Hz, 2H) ; C NMR (150 MHz, CDCl3): δ 159.7, 158.6, 150.8, 140.7, 134.1, 132.9, 131.3, 131.1, 130.3, 130.2, 130.1, 126.5, 116.3, 114.2, 113.8, 113.79, 113.3, 67.2, 55.3, 25.3 ; UV/Vis (MeOH): max = 275 nm; HRMS (EI): calcd for C26H22O3 [M]+ 382.15690, found 382.15644.

(E)-trimethyl((4-(trimethylsilyl)-2H-cyclopenta[de]chromen-5(3H)-ylidene)methyl)silane (2e)

Si Chromatographic purification (15% ethyl acetate in hexanes) afforded compound 1 2e (74%) as a yellow oil. Rf=0.4 (20% ethyl acetate in hexanes); H NMR (600

Si MHz, CDCl3): δ 7.22 (d, J= 7.5 Hz, 1H), 7.07 (t, J= 7.7 Hz, 1H), 6.73 (d, J= 8.0 Hz, 1H), 6.54 (s, 1H), 4.28 (t, J= 5.9 Hz, 2H), 2.99 (t, J= 5.8 Hz, 2H), 0.34 (s, 9H), 13 0.30 (s, 9H) ; C NMR (150 MHz, CDCl3): δ 159.7, 150.9, 146.0, 138.2, 136.7, 131.5, 127.3, 116.5, 114.2, 67.2, 27.7, 1.3, 0.2 ; UV/Vis (MeOH): max = 224 nm; HRMS (EI): calcd for C18H26OSi2 [M]+ 314.1522, found 314.1522.

(E)-4-(naphthalen-1-yl)-5-(naphthalen-1-ylmethylene)-3,5-dihydro-2H- cyclopenta[de]chromene (2f)

O Chromatographic purification (15% ethyl acetate in hexanes) afforded compound 1 2f (80%) as a yellow oil. Rf=0.5 (15% ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.08 (m, 1H), 7.96 (m, 1H), 7.92 (dd, J= 6.8, 2.7 Hz, 1H), 7.87 (d, J= 7.8 Hz, 2H), 7.79 (d, J= 8.6 Hz, 1H), 7.77 (d, J= 7.0 Hz, 1H), 7.61 (m, 2H), 7.55 (m, 2H), 7.51 (m, 1H), 7.47 (m, 1H), 7.39 (m, 1H), 7.33 (s, 1H), 6.83 (t, J= 7.8 Hz, 1H), 6.77 (d, J= 4.1 Hz, 1H), 6.71 (d, J= 7.4 Hz, 1H), 4.33 (t, J= 5.8 Hz, 2H), 2.80 (t, J= 13 5.7 Hz, 2H) ; C NMR (150 MHz, CDCl3): δ 150.9, 144.3, 134.4, 134.2, 133.8, 133.5, 133.0, 132.5, 132.4, 131.6, 131.5, 130.1, 128.7, 128.65, 128.4, 128.36, 128.0, 127.4, 126.9, 126.7, 126.2, 126.1, 126.0, 125.9, 125.3, 125.2, 125.1, 120.1, 116.9, 114.9, 67.2, 25.4 ; UV/Vis (MeOH): max = 320 nm; HRMS (EI): calcd for C32H22O [M]+ 422.1671, found 422.1664.

2-(4-fluorophenyl)-4-((4-fluorophenyl)ethynyl)benzofuran (4)

F Chromatographic purification (10% ethyl acetate in hexanes) afforded compound 1 O 4 (38%) as a red brown solid. Rf=0.8 (10% ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 7.88 (m, 2H), 7.60 (m, 2H), 7.50 (d, J= 8.2 Hz, 1H), 7.41 (dd, J= 2.7, 0.6 Hz, 1H), 7.26 (t, J= 5.2 Hz, 1H), 7.16 (m, 3H), 7.09 (tt, J= 8.7, 1.9 13 F Hz, 2H) ; C NMR (150 MHz, CDCl3): δ 163.9, 163.5, 155.7, 154.4, 133.6, 133.5, 131.3, 127.0, 126.97, 126.5, 124.1, 116.0 (d, J= 22.0 Hz), 115.7 (d, J= 22.2 Hz), 115.4, 111.5, 100.7, 91.5, 86.8; HRMS (EI): calcd for C22H12OF2 [M]+ 330.08563, found 330.08580.

2,3-bis((4-fluorophenyl)ethynyl)phenol (5)

F OH Chromatographic purification (10% ethyl acetate in hexanes) afforded compound 1 5 (55%) as a red orange oil. Rf=0.2 (10% ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 7.55 (m, 2H), 7.51 (m, 2H), 7.23 (t, J= 15.9 Hz, 1H), 7.13 (dd, F J= 2.9, 0.9 Hz, 1H), 7.08 (m, 2H), 7.04 (m, 2H), 6.97 (dd, J= 8.3, 1.0 Hz, 1H), 13 5.91 (bs, 1H) ; C NMR (150 MHz, CDCl3): δ 163.6 (d, J= 36.2 Hz), 162.0 (d, J= 35.7 Hz),

156.4, 133.6, 133.5, 129.8, 125.8, 124.1, 119.2, 118.5, 115.9 (d, J= 22.7 Hz), 115.7 (d, J= 22.0 Hz), 114.8, 112.0, 99.0, 92.3, 87.6, 81.8; HRMS (EI): calcd for C22H12OF2 [M]+ 330.08563, found 330.08483.

13-methyl-11-(p-tolyl)-1,2,11,19c- tetrahydrobenzo[6,7]benzo[1',2']fluoreno[3',4':4,5]indeno[1,2,3-de]chromene (13a)

& Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 13a as a mixture of diastereomers X=Br (26%) X=I (52%) as a dark yellow oil. The oil crystallized upon slow evaporation in a 3:1 mixture of methanol:hexane to provide crystals of one of the individual diastereomers while the other diastereomer remained an oil. 1 These diastereomers were separated by filtration. Rf=0.2 (15% ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 9.08 (d, J= 8.3 Hz, 1H), 9.02 (d, J= 7.7 Hz, 1H), 8.50 (d, J= 8.3 Hz, 1H), 7.91 (d, J= 8.0 Hz, 1H), 7.86 (d, 7.4 Hz, 1H), 7.73 (t, J= 7.7 Hz, 1H), 7.52 (m, 2H), 7.44 (m, 2H), 7.34 (d, J= 7.8 Hz, 2H), 7.23 (s, 1H), 7.15 (d, J= 7.9 Hz, 2H), 7.13 (t, J= 7.9 Hz, 1H), 7.02 (d, J= 8.1 Hz, 1H), 6.74 (d, J= 8.0 Hz, 1H), 5.28 (s, 1H), 4.97 (td, J= 12.6, 4.7 Hz, 1H), 4.69 (dd, J= 11.7, 6.3 Hz, 1H), 3.53 (dd, J= 14.2, 3.5 Hz, 1H), 2.35 (s, 3H), 2.34 (s, 3H), 2.28 (m, 13 1H), 1.98 (m, 1H) ; C NMR (150 MHz, CDCl3): δ 153.7, 150.1, 147.9, 139.3, 138.3, 136.6, 136.53, 136.5, 135.8, 131.1, 130.2, 129.94, 129.9, 129.8, 129.7, 129.5, 129.48, 128.9, 128.8, 128.7, 128.2, 127.9, 127.7, 127.4, 127.2, 127.1, 125.4, 125.1, 124.8, 124.5, 124.3, 123.4, 116.2, 114.8, 65.2, 51.9, 38.7, 30.8, 21.4, 21.1 ; UV/Vis (MeOH): max = 421 nm; HRMS (EI): calcd nd for C42H30O [M]+ 550.2297, found 550.2253. The 2 diastereomer was also a yellow oil. 1 Rf=0.2 (15% ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.98 (d, J= 8.2 Hz, 2H), 8.50 (d, J= 8.3 Hz, 1H), 7.96 (d, J= 8.0 Hz, 1H), 7.80 (d, J= 7.1 Hz, 1H), 7.72 (t, J= 7.4 Hz, 1H), 7.54 (d, J= 7.6 Hz, 1H), 7.49 (t, J= 7.6 Hz, 1H), 7.43 (m, 2H), 7.13 (m, 2H), 7.04 (m, 3H), 6.89 (m, 2H), 6.76 (d, J= 7.9 Hz, 1H), 5.61 (s, 1H), 5.30 (s, 1H), 4.97 (td, J= 12.4, 4.4 Hz, 1H), 4.69 (dd, J= 11.4, 7.2 Hz, 1H), 3.53 (dd, J= 14.0, 4.0 Hz, 1H), 2.33 (s, 3H), 2.29 (s, 3H), 1.97 (m, 1H) 13 ; C NMR (150 MHz, CDCl3): δ 154.7, 150.1, 145.4, 139.2, 138.3, 138.0, 137.0, 136.5, 134.9, 133.6, 132.5, 130.3, 130.1, 129.9, 129.8, 129.4, 129.3, 129.2, 129.1, 128.9, 128.7, 128.6, 127.7, 127.1, 125.2, 124.9, 124.5, 124.3, 123.3, 123.1, 121.7, 118.4, 115.0, 113.3, 65.2, 51.8, 30.8, 29.7, 21.7, 21.6 ; UV/Vis (MeOH): max = 498 nm; HRMS (EI): calcd for C42H30O [M]+ 550.2297, found 550.2290.

11-phenyl-1,2,11,19c-tetrahydrobenzo[6,7]benzo[1',2']fluoreno[3',4':4,5]indeno[1,2,3- de]chromene (13b)

O O H H Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 13b as a mixture of diastereomers, 1:1.1, X=Br (35%) X=I (55%) as a orange oil. Rf=0.3 (10% ethyl 1 acetate in hexanes); H NMR (700 MHz, CDCl3): δ 9.07 (d, J= 7.9 Hz, 1H), 9.02 (t, J= 8.9 Hz, 2H), 8.92 (d, J= 8.5 Hz, 2H), H H 8.50 (d, J= 7.6 Hz, 2H), 8.47 (d, J= 8.2 Hz, 1H), 8.12 (d, J= 7.9 & Hz, 1H), 8.08 (d, J= 7.28 Hz, 2H), 7.84 (d, J= 7.8 Hz, 2H), 7.79 (d, J= 8.5 Hz, 2H), 7.69 (q, J= 7.0 Hz, 2H), 7.56 (d, J= 7.6 Hz, 3H), 7.53 (q, J= 7.1 Hz, 2H), 7.50 (s, 2H), 7.44 (m, 7H), 7.39 (s, 2H), 7.35 (t, J= 7.4 Hz, 3H), 7.30 (m, 5H), 7.23 (m, 7H), 7.17 (m, 4H), 7.06 (d, J= 7.6 Hz, 1H), 7.01 (t, J= 8.1 Hz, 2H), 6.76 (t, J= 7.7 Hz, 2H), 5.68 (s, 1H), 5.35 (s, 1H), 5.06 (t, J= 6.1 Hz, 2H), 4.70 (m, 2H), 3.02 (d, J= 13.7 Hz, 2H), 2.67 (m, 2H), 1.83 (m, 13 2H) ; C NMR (150 MHz, CDCl3): δ 153.9, 149.6, 144.1, 142.2, 140.7, 136.4, 134.2, 132.6, 131.1, 130.1, 129.2, 129.1, 128.9, 128.8, 128.6, 128.4, 127.8, 127.2, 127.17, 127.1, 126.8, 126.7, 126.6, 126.1, 124.5, 124.3, 124.2, 124.0, 123.7, 123.5, 121.0, 116.0, 115.4, 112.9, 111.2, 64.1, 54.9, 54.4, 43.1, 31.4, 29.7 ; UV/Vis (MeOH): max = 465 nm; HRMS (EI): calcd for C40H26O [M]+ 522.19837, found 522.19865.

13-methoxy-11-(4-methoxyphenyl)-1,2,11,19c- tetrahydrobenzo[6,7]benzo[1',2']fluoreno[3',4':4,5]indeno[1,2,3-de]chromene (13c)

O O H H Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 13c as a mixture of diastereomers, 1:1.3, X=Br (32%) X=I (55%) as a yellow-orange oil. Rf=0.2 (10% 1 ethyl acetate in hexanes); H NMR (700 MHz, CDCl3): δ 9.08 (d, O O H H J= 8.3 Hz, 1H), 9.03 (m, 2H), 8.98 (t, J= 7.7 Hz, 2H), 8.50 (d, J=

& 8.5 Hz, 2H), 8.18 (m, 1H), 8.03 (d, J= 8.6 Hz, 0.5H), 7.99 (d, J=

O O 8.3 Hz, 1.5 Hz), 7.94 (d, J= 8.7 Hz, 1H), 7.84 (m, 2H), 7.78 (m, 1H), 7.72 (q, J= 3.2 Hz, 2H), 7.66 (m, 1H), 7.63 (d, J= 7.7 Hz, 1H), 7.54 (t, J= 8.5 Hz, 2H), 7.50 (q, J= 3.9 Hz, 3H), 7.42 (m, 5H), 7.36 (d, J= 8.3 Hz, 3H), 7.17 (m, 1H), 7.13 (q, J= 7.8 Hz, 2H), 6.96 (m, 2H), 6.84 (m, 1H), 6.76 (m, 8H), 5.58 (s, 1H), 5.26 (s, 1H), 4.97 (m, 2H), 4.76 (m, 1H), 4.70 (m, 3H), 4.62 (dd, J= 12.0, 4.4 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H), 3.78 (s, 2H), 3.75 (s, 2H), 3.53 (d, J= 11.0 Hz, 2H), 3.04 (d, J= 12.5 Hz, 1H), 1.96 (m, 13 2H) ; C NMR (150 MHz, CDCl3): δ 159.0, 158.9, 158.8, 158.7, 158.6, 158.4, 153.6, 153.58, 152.5, 152.0, 151.9, 144.1, 142.0, 136.5, 136.4, 135.5, 135.4, 134.8, 134.7, 134.0, 133.4, 133.1, 130.9, 129.8, 129.3, 129.2, 129.1, 129.0, 128.9, 128.8, 128.75, 128.7, 128.65, 126.6, 128.1, 127.9, 127.4, 127.3, 127.2, 126.9, 125.4, 125.2, 124.7, 124.5, 124.3, 124.2, 124.1, 124.07, 124.0, 123.95, 123.9, 116.1, 116.0, 114.9, 114.6, 114.59, 114.4, 114.3, 111.9, 111.8, 111.7, 110.9, 110.2, 68.2, 65.1, 55.5, 55.4, 55.2, 55.16, 54.1, 53.5, 42.2, 42.1, 30.9, 30.8, 29.7, 29.6 ; UV/Vis (MeOH): max = 428 nm; HRMS (EI): calcd for C42H30O3 [M]+ 582.2195, found 582.2196.

APPENDIX B

COMPUTATIONAL COORDINATES FOR RADICAL CASCADE (CH. 2)

Methods: All stationary point geometries were optimized by DFT computations at the UB3LYP level with the 6-31g(d,p) basis set using Gaussian 03 program (see below the reference). Total energies are given in Hartrees followed by the Cartesian coordinates for each structure. Frequency calculations were carried out for all structures to confirm that every Transition State (TS) has only one imaginary frequency. All radical reactants, products and intermediates have no imaginary numbers indicating that they are true minima.

Gaussian 03, Revision E.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, and J. A. Pople, Gaussian, Inc., Wallingford, CT, 2004.

Enediyne Cascade (7a) Total Energy= -999.862076

C 1.27657700 -3.51531300 -0.37511500 C 0.81134300 -2.19256300 -0.27006500 C 1.74492000 -1.11351800 -0.28692600 C 3.12445600 -1.41305600 -0.38298300 C 3.55942200 -2.73252400 -0.49111100 C 2.63654000 -3.77954800 -0.49383900 H 0.55446400 -4.32428100 -0.36499200 H 4.62421200 -2.91687200 -0.58165600 H 2.98285700 -4.80488300 -0.57990000

C 1.29385300 0.23285200 -0.25535900 C 0.88395100 1.37848700 -0.24612000 C -0.58242700 -1.94010800 -0.14245500 C -1.77660200 -1.74538600 -0.01763200 C 0.38486000 2.71246500 -0.25180100 C -0.98841400 2.95774500 -0.45750100 C -1.47676100 4.26096500 -0.46319800 C -0.61147200 5.33969800 -0.26491900 C 0.75108100 5.10765500 -0.06254900 C 1.24944200 3.80812200 -0.05598500 H -1.65565000 2.11747400 -0.61926500 H -2.53624900 4.43632600 -0.62534400 H 1.42822200 5.94307100 0.08945900 H 2.30791200 3.62538400 0.09776800 C -3.16981100 -1.49232500 0.13905100 C -4.12407700 -2.46652500 -0.21613800 C -5.48320200 -2.20951500 -0.06065900 C -5.91539800 -0.98342200 0.45046500 C -4.97769500 -0.01164900 0.80821900 C -3.61649000 -0.25899100 0.65615500 H -3.78512100 -3.41739600 -0.61404300 H -6.20834700 -2.96846300 -0.33933200 H -5.30862500 0.94182600 1.20943400 H -2.88426200 0.48971100 0.94048000 O 4.05681800 -0.40559200 -0.44574600 C 4.33219100 0.29120200 0.79118800 H 4.88098400 1.18673600 0.46273200 H 3.39754700 0.63568300 1.24846500 C 5.13516200 -0.52046200 1.74176700 H 5.95469600 -1.12826600 1.37391700 H 4.99693100 -0.42531300 2.81289900 H -0.99621200 6.35512400 -0.26992300 H -6.97660000 -0.78684200 0.57030400

(7b) Total Energy= -1078.5039486

C 1.72753200 -3.75838200 -0.41166000 C 1.24007700 -2.44418500 -0.29763900 C 2.15730000 -1.35084600 -0.28607300 C 3.54259600 -1.62885700 -0.36307500

C 3.99956300 -2.93992300 -0.48066000 C 3.09293800 -4.00072600 -0.51174200 H 1.01768000 -4.57815100 -0.42331900 H 5.06843800 -3.10684900 -0.55595600 H 3.45621900 -5.01957200 -0.60502500 C 1.68504500 -0.01211100 -0.24535600 C 1.25662200 1.12685900 -0.22879300 C -0.15914700 -2.21476900 -0.18989000 C -1.35828200 -2.04002400 -0.08212800 C 0.73543300 2.45163100 -0.22532200 C -0.63539500 2.68309300 -0.45579700 C -1.14229900 3.97798200 -0.45543000 C -0.31420800 5.08561000 -0.22512000 C 1.05025500 4.85142300 -0.00241800 C 1.57201100 3.56264100 -0.00076800 H -1.28921000 1.83818200 -0.64629300 H -2.20193700 4.13417700 -0.64151400 H 1.71487300 5.69439300 0.16968200 H 2.63190100 3.40211400 0.16814100 C -2.75684200 -1.81003700 0.05455600 C -3.69414600 -2.79824400 -0.30383700 C -5.05754100 -2.56255800 -0.16329100 C -5.53943000 -1.34384800 0.33460400 C -4.60299600 -0.36477800 0.69639600 C -3.23694100 -0.58561500 0.56108600 H -3.33994100 -3.74849800 -0.69007800 H -5.76337400 -3.34024600 -0.44400700 H -4.95142400 0.58501700 1.09447700 H -2.52578400 0.17934300 0.85580800 O 4.46139500 -0.60707600 -0.39820700 C 4.70153500 0.08222800 0.84949200 H 5.24596100 0.98750800 0.54059100 H 3.75335900 0.41176600 1.28974600 C 5.49402400 -0.72742200 1.81060300 H 6.32243000 -1.33006700 1.45437600 H 5.33984200 -0.63347400 2.87970100 C -0.87767500 6.48560200 -0.19316600 H -1.77457800 6.57054700 -0.81369700 H -1.15913600 6.77626000 0.82701400 H -0.14818800 7.21959100 -0.54859300 C -7.02143500 -1.08322300 0.45437400 H -7.24335500 -0.40803100 1.28628700 H -7.41643300 -0.61595000 -0.45670200 H -7.58007600 -2.01059700 0.61133800

(7c) Total Energy= -1198.3252867

C 1.66161800 -3.75550400 -0.41702100 C 1.18839200 -2.43675300 -0.29925900 C 2.11668700 -1.35327600 -0.28606600 C 3.49891000 -1.64448300 -0.36563500 C 3.94205700 -2.96002300 -0.48698500 C 3.02454400 -4.01128100 -0.51941400 H 0.94374400 -4.56819500 -0.42958900 H 5.00892300 -3.13804900 -0.56448800 H 3.37721300 -5.03349100 -0.61569700 C 1.65820800 -0.00970900 -0.24250800 C 1.24148100 1.13329000 -0.22519500 C -0.20828100 -2.19200300 -0.18867900 C -1.40471800 -2.00283300 -0.07833900 C 0.73320500 2.46300000 -0.22391900 C -0.63659100 2.70321800 -0.46049900 C -1.14275000 3.99863700 -0.46221200 C -0.27312900 5.05846900 -0.22590300 C 1.08373700 4.86197200 0.00900400 C 1.58308200 3.56372900 0.00837700 H -1.29521600 1.86257800 -0.65088500 H -2.19269900 4.19829800 -0.64581400 H 1.72591200 5.71762500 0.18610400 H 2.63883400 3.38976100 0.18612600 C -2.79996100 -1.75577400 0.06259900 C -3.74924800 -2.71656500 -0.34143500 C -5.11193100 -2.47316900 -0.20450600 C -5.52523500 -1.26212100 0.34092900 C -4.61928100 -0.29049000 0.75377400 C -3.25826800 -0.54082800 0.61346800 H -3.40613300 -3.65400700 -0.76563800 H -5.85307000 -3.20247900 -0.51223700 H -4.98585300 0.63780000 1.17789400 H -2.53391300 0.19930100 0.93650600 O 4.42568100 -0.63053200 -0.39870700 C 4.68526300 0.04089600 0.85571900 H 5.23494400 0.94456800 0.55201800 H 3.74422000 0.37276400 1.30952600 C 5.47986600 -0.78785500 1.79843500 H 6.30705400 -1.38338900 1.42773300

H 5.32785600 -0.71675200 2.86953800 F -0.76060100 6.31553900 -0.22586000 F -6.84531000 -1.02280000 0.47476800

(7d) Total Energy= -1228.9136958

C 0.97782600 -4.33463000 -0.40861600 C 0.83531600 -2.93983000 -0.29419100 C 1.99771200 -2.11153600 -0.28476400 C 3.26849500 -2.72919500 -0.36331800 C 3.38208200 -4.11265100 -0.48164600 C 2.23811900 -4.91214000 -0.51123400 H 0.08479800 -4.94989100 -0.41919300 H 4.37478000 -4.54223700 -0.55949300 H 2.33385700 -5.98955100 -0.60526000 C 1.87685200 -0.69720500 -0.24501200 C 1.74964400 0.51330100 -0.22917600 C -0.46214600 -2.36862600 -0.18707900 C -1.58259500 -1.90548900 -0.08235700 C 1.57624600 1.92537100 -0.22636100 C 0.30894900 2.49593000 -0.48340500 C 0.13332800 3.86927300 -0.47972600 C 1.21845500 4.72179200 -0.21934300 C 2.48335500 4.17578900 0.03419000 C 2.65277000 2.79272700 0.02800300 H -0.53096400 1.84218400 -0.69409800 H -0.83654200 4.31286500 -0.67859900 H 3.33612700 4.81323400 0.23439200 H 3.63478700 2.37382600 0.22211200 C -2.88361000 -1.34411200 0.04657800 C -4.03157500 -2.09020300 -0.27189600 C -5.30771300 -1.54424100 -0.15021700 C -5.45942200 -0.22604200 0.29901900 C -4.32286900 0.53199500 0.62422500 C -3.05783100 -0.01737000 0.50115800 H -3.91761500 -3.11101900 -0.62178900 H -6.16887700 -2.14955800 -0.40620400 H -4.46283400 1.54933400 0.97408200 H -2.18381300 0.57013100 0.76253300 O 4.41536200 -1.97093600 -0.40105100

C 4.82186400 -1.36253700 0.84466300 H 5.58388700 -0.63086300 0.53531200 H 3.99054700 -0.79589400 1.27999700 C 5.37429900 -2.34476700 1.81310200 H 6.01286300 -3.14835400 1.46270000 H 5.25075400 -2.20531100 2.88123800 O -6.65580100 0.40768800 0.45532600 O 0.93866400 6.05558800 -0.23741100 C -7.84336700 -0.30831600 0.15023600 H -8.66720500 0.37922100 0.34592400 H -7.87184800 -0.61516800 -0.90292200 H -7.95497000 -1.19570500 0.78592700 C 1.99528700 6.96954800 0.01566400 H 1.55369100 7.96477200 -0.04937900 H 2.42098400 6.82834100 1.01717000 H 2.79496000 6.87990800 -0.73034800

(7e) Total Energy= -1355.1371007

C 0.52589000 -3.44594500 -0.35752400 C 0.27964300 -2.06656600 -0.24748300 C 1.36935300 -1.14934400 -0.28970000 C 2.68081200 -1.66132100 -0.42803100 C 2.89813800 -3.03357600 -0.54527300 C 1.82332600 -3.92189900 -0.51388200 H -0.31517800 -4.12963200 -0.32676600 H 3.91736700 -3.38281300 -0.66823200 H 2.00089200 -4.98901700 -0.60567000 C 1.14076900 0.25487100 -0.23239100 C 0.93900200 1.45883000 -0.18887100 C -1.06166200 -1.60525000 -0.10363600 C -2.22373900 -1.25104700 0.02000500 O 3.76015100 -0.81778300 -0.52442900 C 4.18561100 -0.17111500 0.69814600 H 4.88186700 0.60419200 0.34509200 H 3.34067900 0.34553400 1.16695600 C 4.84541900 -1.10710600 1.64411100 H 5.53008200 -1.86061800 1.27012700 H 4.75198700 -0.97499900 2.71617500 Si 0.59355900 3.26608400 -0.16371500

Si -3.97276400 -0.70976600 0.20263400 C 2.09078900 4.18265000 -0.86179200 H 1.91511000 5.26442900 -0.86856800 H 2.98878100 3.99377500 -0.26475500 H 2.30170300 3.87031300 -1.88943800 C 0.27371000 3.80378600 1.61981800 H 1.14387800 3.61348500 2.25631200 H 0.05276800 4.87626500 1.66700600 H -0.57766000 3.26629400 2.04947400 C -0.93121000 3.60064600 -1.22744600 H -0.77076500 3.27830000 -2.26103500 H -1.80504700 3.06510300 -0.84249500 H -1.17085300 4.66996800 -1.24102400 C -4.48263200 0.23928500 -1.34902000 H -5.51968600 0.58482900 -1.26948700 H -3.84669900 1.11656800 -1.50533800 H -4.40602700 -0.39025800 -2.24122600 C -5.05813300 -2.24226300 0.41524300 H -4.76993600 -2.81229500 1.30428800 H -6.11172600 -1.96095900 0.52459300 H -4.97770800 -2.90832700 -0.44980900 C -4.11154500 0.40116800 1.72446100 H -3.81064300 -0.13102700 2.63244800 H -3.47346800 1.28558500 1.62935400 H -5.14328500 0.74429600 1.86217500

(7a TS1) Total Energy= -999.8526834, one negative frequency (-339.6756)

C 1.98757400 -3.17576200 -0.36558600 C 1.40313400 -1.91054700 -0.17848900 C 2.23159300 -0.74733500 -0.10799500 C 3.63113500 -0.91789900 -0.21147300 C 4.18517500 -2.18607700 -0.40289500 C 3.36629200 -3.30885300 -0.48820900 H 1.33970800 -4.04328700 -0.42443300 H 5.26413100 -2.26079800 -0.48407000 H 3.80527900 -4.29011500 -0.64048300 C 1.62288600 0.54581900 0.01491700 C 0.70983900 1.36676700 -0.10437100 C -0.01402000 -1.82350700 -0.08837700 C -1.22930000 -1.82698800 -0.02944600

C -0.20612900 2.44515100 -0.15384900 C -1.21261500 2.58199400 0.82984900 C -2.11154500 3.64255100 0.77456900 C -2.02971100 4.58634200 -0.25338400 C -1.03900500 4.46170900 -1.23157900 C -0.13589700 3.40485400 -1.18894800 H -1.26963400 1.85046600 1.62925600 H -2.87733800 3.73652600 1.53911100 H -0.97180600 5.19222700 -2.03249200 H 0.63082100 3.30338300 -1.94997400 C -2.65256200 -1.83106500 0.03957000 C -3.37935600 -0.62336500 0.02014400 C -4.76964600 -0.63981100 0.08550400 C -5.45930500 -1.85166400 0.17058200 C -4.74839200 -3.05401200 0.18951600 C -3.35824200 -3.04861100 0.12419000 H -2.84257500 0.31686600 -0.04830000 H -5.31779600 0.29770000 0.06849500 H -5.27934700 -3.99922400 0.25479200 H -2.80274800 -3.98068000 0.13844300 O 4.50776100 0.13143700 -0.16577200 C 4.47769800 0.90853900 1.06450700 H 4.49764900 0.22073700 1.91894700 H 5.43477800 1.44691800 1.04156400 C 3.32067700 1.83354000 1.13766200 H 3.27035900 2.65502200 0.43225700 H 2.79163300 1.95859700 2.07522500 H -2.73279900 5.41286500 -0.29173600 H -6.54407000 -1.85932500 0.22111500

(7b TS1) Total Energy= -1078.4945359, one negative frequency (-341.7233)

C 2.56397500 -3.25402200 -0.39693700 C 1.93016300 -2.01469600 -0.19597200 C 2.71311000 -0.82150800 -0.11006500 C 4.11816600 -0.93631800 -0.21497700 C 4.72172000 -2.17935300 -0.42007200 C 3.94692300 -3.33215000 -0.51878900 H 1.95041300 -4.14535100 -0.46718500 H 5.80280300 -2.21104400 -0.50136600 H 4.42366600 -4.29392300 -0.68181100

C 2.05703800 0.44622300 0.03187600 C 1.11346800 1.23360800 -0.07924200 C 0.51075900 -1.98315800 -0.10792300 C -0.70388400 -2.03345300 -0.05215400 C 0.15809800 2.27679300 -0.11561600 C -0.86086500 2.36346600 0.85839400 C -1.79774100 3.39074500 0.81164000 C -1.76163300 4.36789300 -0.19284800 C -0.74949800 4.27783600 -1.16203000 C 0.19252900 3.25834900 -1.13231900 H -0.90279200 1.61793100 1.64578500 H -2.57242900 3.43787400 1.57280700 H -0.70321300 5.02075100 -1.95463100 H 0.96379400 3.20195500 -1.89356800 C -2.12569800 -2.09024500 0.00752900 C -2.90088000 -0.91371100 -0.01011500 C -4.28863300 -0.98383600 0.04140600 C -4.95607500 -2.21480800 0.11457500 C -4.18115300 -3.38300100 0.12779300 C -2.79265800 -3.32946400 0.07589700 H -2.40341400 0.04855800 -0.07094200 H -4.86761100 -0.06380600 0.02126200 H -4.67494500 -4.35028300 0.17731200 H -2.20922600 -4.24451000 0.08408400 O 4.95169700 0.14730900 -0.15763800 C 4.89879900 0.90075200 1.08740100 H 4.96286200 0.19890100 1.92812900 H 5.82837900 1.48501100 1.06258200 C 3.69936000 1.76708300 1.19262400 H 3.60867200 2.60958000 0.51669600 H 3.16636100 1.83431200 2.13384100 C -2.76515500 5.49460300 -0.22645700 H -2.31125400 6.44073600 0.09378000 H -3.15564100 5.65299700 -1.23728400 H -3.61251700 5.29652000 0.43573900 C -6.46168600 -2.27900500 0.20282700 H -6.80004800 -2.23418300 1.24591000 H -6.93004100 -1.44296000 -0.32524900 H -6.84868900 -3.20927200 -0.22346800

(7c TS1) Total Energy= -1198.3159122, one negative frequency (-334.4268)

C 2.51862500 -3.25325500 -0.38530300 C 1.89617100 -2.00785400 -0.18972300 C 2.68817400 -0.82002500 -0.10694200 C 4.09267300 -0.94720700 -0.20808900 C 4.68490700 -2.19673400 -0.40919100 C 3.90111800 -3.34311700 -0.50545800 H 1.89780700 -4.13968600 -0.45290600 H 5.76578900 -2.23783700 -0.48807100 H 4.37022900 -4.30921100 -0.66449600 C 2.03554400 0.45089500 0.02562300 C 1.08932700 1.23495600 -0.08175600 C 0.47674200 -1.96489000 -0.10323000 C -0.73802100 -2.00654100 -0.04786800 C 0.13092700 2.27589900 -0.11607900 C -0.86400600 2.37541800 0.88452200 C -1.80877700 3.39533900 0.85170700 C -1.76035600 4.32321600 -0.18464300 C -0.79783800 4.25984100 -1.18806200 C 0.14281400 3.23716700 -1.15299200 H -0.88004200 1.64511800 1.68641800 H -2.57388200 3.48503600 1.61511700 H -0.79816500 5.00385000 -1.97705000 H 0.89825700 3.16791100 -1.92818000 C -2.16015500 -2.05331200 0.01144800 C -2.92445700 -0.86851900 -0.02011000 C -4.31348000 -0.91632200 0.03507100 C -4.93969600 -2.15536300 0.12214100 C -4.22043100 -3.34552400 0.15479600 C -2.83182600 -3.29035500 0.09851600 H -2.41780500 0.08776800 -0.09038900 H -4.91362900 -0.01343100 0.00981100 H -4.74960800 -4.28961300 0.22257100 H -2.25200100 -4.20678600 0.12224100 O 4.94000900 0.12505400 -0.15237700 C 4.87596400 0.90487700 1.07392200 H 4.89310800 0.22131300 1.93185100 H 5.82406500 1.45974400 1.06570700 C 3.70180500 1.80902500 1.12204000 H 3.63830000 2.61130300 0.39576400

H 3.16966300 1.94816900 2.05590100 F -2.67448800 5.31360300 -0.21740200 F -6.28625100 -2.20468900 0.17658900

(7d TS1) Total Energy= -1228.9043499, one negative frequency (-346.1257)

C 2.57007600 -3.62384400 -0.54523800 C 2.06733500 -2.33822400 -0.27371800 C 2.97041200 -1.23976200 -0.12808800 C 4.35590200 -1.49339400 -0.24747600 C 4.82811600 -2.77855100 -0.52394100 C 3.93731100 -3.83775900 -0.67998300 H 1.86772400 -4.44209200 -0.65996500 H 5.89998400 -2.91769500 -0.61430900 H 4.31140600 -4.83347100 -0.89822800 C 2.45492900 0.08152300 0.08711100 C 1.60179000 0.97027500 0.00839600 C 0.65930400 -2.16419400 -0.17370400 C -0.55403000 -2.09019400 -0.11010800 C 0.76256600 2.10812000 0.01568600 C -0.25651700 2.25899000 0.98884300 C -1.08111900 3.37087200 0.98963700 C -0.91989000 4.37565800 0.02051400 C 0.08254400 4.24671700 -0.95059000 C 0.90789800 3.12559100 -0.94932300 H -0.38290300 1.48868500 1.74248500 H -1.86047300 3.49197100 1.73470900 H 0.22633700 5.00789000 -1.70789600 H 1.67920700 3.02699200 -1.70608500 C -1.97277900 -2.00272100 -0.03928300 C -2.62678800 -0.75098000 0.00781200 C -4.00777500 -0.67395400 0.07534000 C -4.78405200 -1.84379900 0.09796100 C -4.15434700 -3.09423000 0.05072000 C -2.76458300 -3.16449600 -0.01788200 H -2.03466500 0.15774600 -0.01154000 H -4.51546800 0.28421000 0.11082200 H -4.73111600 -4.01113400 0.06588200 H -2.27944200 -4.13449400 -0.05473700 O 5.29441500 -0.50362300 -0.13550100

C 5.32648500 0.16849200 1.15734100 H 5.34094800 -0.59192800 1.94799500 H 6.30391800 0.66869500 1.15010200 C 4.21042400 1.12763000 1.34597200 H 4.19970600 2.03325900 0.75053300 H 3.68375100 1.15870000 2.29262500 O -1.78172600 5.42704600 0.11095900 O -6.13281100 -1.65692900 0.16624400 C -1.66878500 6.47585600 -0.83996100 H -1.83609300 6.11444200 -1.86236400 H -2.44435100 7.19848900 -0.58320500 H -0.68797500 6.96501600 -0.78769600 C -6.97090400 -2.80246000 0.19300000 H -6.77020100 -3.43021000 1.07039800 H -7.99316200 -2.42586100 0.24756400 H -6.85730500 -3.40813200 -0.71496100

(7e TS1) Total Energy= -1355.1240176, one negative frequency (-384.4498)

C 1.07330900 -3.28318900 -0.40052400 C 0.78382300 -1.92505400 -0.18664700 C 1.84396000 -0.96853100 -0.10039200 C 3.17251100 -1.44711400 -0.20067500 C 3.43214000 -2.80293900 -0.42033400 C 2.38879000 -3.71559300 -0.53128400 H 0.24944900 -3.98465200 -0.46867800 H 4.46911300 -3.11070400 -0.49917000 H 2.60137500 -4.76612000 -0.70400100 C 1.51356600 0.42734000 0.00844800 C 0.75844800 1.40338100 -0.12889400 C -0.58886000 -1.55527300 -0.06754400 C -1.78980600 -1.35372100 0.03379300 O 4.27074500 -0.63733000 -0.12698400 C 4.34372800 0.20378100 1.05176700 H 4.13702100 -0.40568700 1.94086100 H 5.40138300 0.50078600 1.08635200 C 3.43398900 1.37208600 0.96906000 H 3.60768300 2.09238400 0.17742300 H 2.98869200 1.75285800 1.88138500 Si -0.14248700 2.99823800 -0.27292200

Si -3.60563300 -1.11303400 0.20534700 C 1.08183200 4.42647500 -0.06666500 H 0.56504100 5.38931200 -0.15301700 H 1.57106000 4.39748900 0.91218900 H 1.86272600 4.39792600 -0.83348300 C -1.45762800 3.08521800 1.08174500 H -1.00659400 3.02821900 2.07760100 H -2.01815700 4.02494000 1.01972700 H -2.17097600 2.26044900 0.99119400 C -0.94778100 3.09177800 -1.97953100 H -0.19582300 3.03978500 -2.77344500 H -1.65174400 2.26808300 -2.13303800 H -1.49682400 4.03301700 -2.09835000 C -3.98558600 -0.53699500 1.96476300 H -3.47847400 0.40486500 2.19695800 H -5.06219000 -0.38032100 2.09781200 H -3.66127700 -1.27941000 2.70098500 C -4.18505300 0.17818900 -1.04712500 H -3.70443100 1.14669800 -0.87627800 H -3.95437400 -0.13388500 -2.07079200 H -5.26881100 0.32620900 -0.97795100 C -4.46224500 -2.76301200 -0.13345400 H -5.54907900 -2.66287800 -0.03407300 H -4.25027300 -3.11987100 -1.14645300 H -4.13160100 -3.53467100 0.56912000

(8a Int) Total Energy= -999.916021

C 2.24334000 -2.88419300 -0.07013800 C 1.64970800 -1.60997800 -0.02237700 C 2.46324200 -0.44280700 0.02777400 C 3.86379100 -0.62003500 -0.00396700 C 4.44056800 -1.89273300 -0.04637000 C 3.62852400 -3.02063400 -0.07251200 H 1.60058700 -3.75667200 -0.10324800 H 5.52264500 -1.96486300 -0.06536100 H 4.07624500 -4.00909700 -0.10699600 C 1.91002100 0.92277500 0.15537300 C 0.63468700 1.23841800 0.05473600 C 0.22647400 -1.54444600 -0.01910500 85

C -0.98682200 -1.65911300 -0.03187500 C -0.46463900 2.09160200 0.05638900 C -0.93742000 2.68869800 -1.15177000 C -2.06238300 3.50012300 -1.14747500 C -2.76385800 3.74338700 0.04139600 C -2.32267500 3.15874500 1.23638800 C -1.20052400 2.34459500 1.25378200 H -0.39866300 2.49703400 -2.07413200 H -2.40024600 3.95034500 -2.07674800 H -2.86402000 3.34220600 2.16021800 H -0.86507600 1.88613500 2.17814600 C -2.40781100 -1.76327700 -0.04787800 C -3.21370200 -0.64392100 -0.34010500 C -4.60046600 -0.76421200 -0.35350800 C -5.20777700 -1.99173900 -0.07853200 C -4.41777800 -3.10676800 0.21144800 C -3.03052100 -2.99798800 0.22747400 H -2.74196700 0.30834800 -0.55478000 H -5.21001200 0.10578300 -0.57959700 H -4.88429200 -4.06387000 0.42584700 H -2.41326800 -3.86154000 0.45308200 O 4.74901700 0.42395700 0.01762100 C 4.22293200 1.70739200 -0.32871000 H 5.01932300 2.41996300 -0.10052500 H 4.02350200 1.73802400 -1.40945900 C 2.95316400 2.00098700 0.45555300 H 2.56660400 2.99199500 0.20381600 H 3.19063400 1.99640500 1.52731900 H -3.64439200 4.37828600 0.03596100 H -6.29019800 -2.07941300 -0.09045300

(8b Int) Total Energy= -1078.5578013

C 2.81416000 -2.92328500 -0.05890700 C 2.18090900 -1.66785100 -0.01635600 C 2.95812700 -0.47576700 0.02774700 C 4.36350400 -0.60983600 -0.00489600 C 4.97965500 -1.86400200 -0.04200800 C 4.20279600 -3.01669600 -0.06193300 H 2.19877500 -3.81547500 -0.08737000 H 6.06343900 -1.90263300 -0.06202600

H 4.68095900 -3.99098900 -0.09226700 C 2.36286400 0.87255900 0.14976100 C 1.07789300 1.14789600 0.04807500 C 0.75649300 -1.64643400 -0.01187200 C -0.45286200 -1.79875000 -0.02301000 C -0.03945200 1.97683500 0.04931800 C -0.53627600 2.55649900 -1.15659900 C -1.68048200 3.33851400 -1.15055700 C -2.39915300 3.58639300 0.03291100 C -1.92316400 3.00573800 1.22276900 C -0.78247700 2.22043800 1.24350500 H -0.00286900 2.37238400 -2.08368800 H -2.03180500 3.77059800 -2.08468400 H -2.46594700 3.17560900 2.14965200 H -0.44027000 1.77410400 2.17143000 C -1.86966600 -1.94228300 -0.03676400 C -2.71136300 -0.84696300 -0.31609100 C -4.09258200 -1.00801300 -0.32932000 C -4.68765900 -2.24992400 -0.06616100 C -3.84621300 -3.33772700 0.20623600 C -2.46342300 -3.19359200 0.22312100 H -2.27166800 0.12180700 -0.52553900 H -4.72353100 -0.15065100 -0.55032800 H -4.28239600 -4.31322300 0.40666000 H -1.82725800 -4.04707000 0.43460600 O 5.21631300 0.46140800 0.01064500 C 4.64995300 1.72632100 -0.34014200 H 5.42428200 2.46427400 -0.11639700 H 4.44788500 1.74619300 -1.42070600 C 3.37271500 1.98317300 0.44480100 H 2.95537300 2.96092600 0.19026700 H 3.61215000 1.98989300 1.51619000 C -3.62378500 4.46689700 0.03174600 H -3.36367500 5.51333900 0.23927600 H -4.13123400 4.44711900 -0.93752300 H -4.34185300 4.15661300 0.79717400 C -6.18911500 -2.40517400 -0.05037100 H -6.59696800 -2.21273200 0.95022600 H -6.67161700 -1.70299600 -0.73687200 H -6.49064900 -3.41815900 -0.33324600

(8c Int) Total Energy= -1198.3792196

C 2.76378500 -2.93512000 -0.06188300 C 2.13814700 -1.67627800 -0.02004100 C 2.92176700 -0.48854200 0.02440900 C 4.32631500 -0.62970700 -0.00672100 C 4.93532500 -1.88758500 -0.04280600 C 4.15215800 -3.03575700 -0.06344900 H 2.14401600 -3.82420800 -0.09099400 H 6.01884800 -1.93249100 -0.06141300 H 4.62497800 -4.01258900 -0.09316600 C 2.33302800 0.86234900 0.14706100 C 1.04858500 1.14062000 0.04547700 C 0.71367600 -1.64592200 -0.01572900 C -0.49663000 -1.78890600 -0.02627000 C -0.06099200 1.98308700 0.05149200 C -0.54894700 2.57209800 -1.15470600 C -1.68541100 3.36713800 -1.15553000 C -2.36305300 3.58310700 0.04440200 C -1.93232500 3.02177700 1.24649800 C -0.79682900 2.22674800 1.25115600 H -0.01310300 2.38989500 -2.08017800 H -2.05635900 3.82395500 -2.06686400 H -2.49181900 3.21502600 2.15548100 H -0.45267100 1.77628700 2.17577700 C -1.91460500 -1.91961600 -0.03964400 C -2.74221000 -0.82009100 -0.34948800 C -4.12662200 -0.95470100 -0.36163800 C -4.68436600 -2.19351900 -0.06329000 C -3.90143300 -3.30092700 0.24569900 C -2.51783900 -3.15972600 0.25621300 H -2.28925400 0.13704300 -0.58106700 H -4.77507100 -0.11815000 -0.59757200 H -4.37815700 -4.24832400 0.47177100 H -1.88865500 -4.01031400 0.49560800 O 5.18402100 0.43667600 0.00972500 C 4.62469400 1.70502000 -0.34036500 H 5.40224100 2.43873900 -0.11457300 H 4.42446700 1.72692100 -1.42115900 C 3.34778600 1.96802300 0.44334200

H 2.93605600 2.94817700 0.18894000 H 3.58546100 1.97258200 1.51505400 F -3.46978000 4.35495900 0.04119200 F -6.02657300 -2.32577900 -0.07436800

(8d Int) Total Energy= -1228.9673393

C 3.00216600 -3.17919300 -0.16799900 C 2.44700500 -1.89033400 -0.06289500 C 3.29695300 -0.75084000 0.01816300 C 4.69115500 -0.97027600 -0.03504800 C 5.22896000 -2.25657700 -0.13257900 C 4.38194000 -3.35750800 -0.19305800 H 2.33267200 -4.03023400 -0.22379600 H 6.30807500 -2.36037300 -0.16738200 H 4.79847200 -4.35721100 -0.27080200 C 2.78699600 0.62642900 0.18905700 C 1.52012600 0.98291900 0.09316800 C 1.02679200 -1.78662700 -0.03243000 C -0.18895900 -1.87908300 -0.01875400 C 0.49918200 1.93306500 0.12974800 C 0.06591500 2.60368400 -1.04845600 C -0.98094100 3.51684300 -1.02494700 C -1.64811700 3.78897500 0.17947600 C -1.24945500 3.12918500 1.35797300 C -0.20861200 2.22218800 1.33776800 H 0.57168800 2.39241900 -1.98500500 H -1.27229000 4.00942700 -1.94518500 H -1.77945800 3.35416900 2.27789900 H 0.08795800 1.71609700 2.25058400 C -1.60968400 -1.95482900 -0.00418400 C -2.40631300 -0.79463000 0.12622500 C -3.78823700 -0.88226000 0.14163400 C -4.42325600 -2.12919600 0.02635400 C -3.65104800 -3.29042800 -0.10516700 C -2.26107100 -3.19597700 -0.11885000 H -1.92452000 0.17226700 0.21842800 H -4.40487900 0.00451500 0.24408600 H -4.11682700 -4.26424100 -0.19649500 H -1.66522500 -4.09735700 -0.21977500 O 5.60899200 0.04537500 0.01575100

C 5.12098700 1.35546800 -0.28204300 H 5.94059900 2.03476000 -0.03450000 H 4.91705400 1.43055100 -1.35994500 C 3.86450500 1.66050100 0.51908000 H 3.50675100 2.67069900 0.30291400 H 4.10829800 1.61354100 1.58859500 O -2.68601200 4.66329900 0.31472400 O -5.78649100 -2.10304600 0.05358200 C -3.13633300 5.35782400 -0.83854100 H -3.50430900 4.66806100 -1.60864200 H -3.95708900 5.99421700 -0.50509700 H -2.34472100 5.98505900 -1.26776300 C -6.48593200 -3.33400000 -0.04655400 H -6.23553600 -4.01020900 0.78065300 H -7.54617500 -3.08249700 0.00414300 H -6.28079100 -3.84062000 -0.99821100

(8e Int) Total Energy= -1355.1795425

C -1.12511200 -3.13277800 0.00121900 C -0.90198200 -1.74450200 -0.02150200 C -2.00169400 -0.84129300 -0.04282300 C -3.30094300 -1.39907900 -0.00847800 C -3.50798300 -2.78146200 0.00685900 C -2.41972800 -3.64464200 0.00522200 H -0.26808300 -3.79648300 0.01158500 H -4.52942600 -3.14570400 0.02906500 H -2.57885700 -4.71848000 0.01915400 C -1.84388100 0.62755700 -0.13680000 C -0.70102800 1.28971900 -0.02390600 C 0.46505500 -1.32583600 -0.02855000 C 1.68278900 -1.19542800 -0.02446900 O -4.44007300 -0.64228200 0.00251600 C -4.28462500 0.73059900 0.36895500 H -5.24875500 1.19967700 0.15788400 H -4.09028800 0.79741300 1.44896900 C -3.15255100 1.37175000 -0.41716400 H -3.05921900 2.42908400 -0.15779300 H -3.38696800 1.30934300 -1.48804500 Si 0.31288500 2.82237500 0.01962400

Si 3.52275100 -1.16113900 0.00441100 C -0.77762000 4.34851700 0.32829200 H -0.15388300 5.24736300 0.40343400 H -1.49307400 4.51183700 -0.48439000 H -1.34084900 4.25905800 1.26316000 C 1.20156500 3.02839500 -1.63702200 H 0.48459600 3.16885800 -2.45268400 H 1.86133200 3.90360300 -1.61831300 H 1.80908400 2.15076900 -1.87556000 C 1.56270200 2.68671500 1.43098900 H 1.05709000 2.58908900 2.39723900 H 2.20258600 1.80928500 1.30212900 H 2.20333400 3.57483600 1.47521000 C 4.10986300 -0.82148200 1.76918300 H 5.20497200 -0.81900600 1.81674600 H 3.75702200 0.14848000 2.13333700 H 3.74608300 -1.58855400 2.46028400 C 4.16679800 0.17617000 -1.16467900 H 5.26245200 0.16615100 -1.19152000 H 3.80637400 0.01762600 -2.18620500 H 3.85094300 1.17484100 -0.84793500 C 4.14434500 -2.85441500 -0.56134800 H 3.80843900 -3.08109900 -1.57827100 H 5.23983100 -2.88743500 -0.55424100 H 3.78111400 -3.65061500 0.09627900

(8a TS2) Total Energy= -999.9112393, one negative frequency (-332.3375)

C -2.07910000 -2.87529400 0.04685800 C -1.58705200 -1.56390800 0.00927900 C -2.48368900 -0.47849900 -0.04377300 C -3.86482600 -0.71412600 -0.03872900 C -4.35512300 -2.02244700 -0.00906200 C -3.45904900 -3.09121600 0.02825800 H -1.38616600 -3.70864800 0.08421400 H -5.42834800 -2.18080900 -0.00922300 H -3.84244100 -4.10684300 0.05304200 C -1.92822400 0.87360100 -0.13744500 C -0.61335800 1.02657600 -0.08408700 C -0.18042000 -1.25761100 0.01040900

C 1.02861900 -1.51401200 0.02836200 C 0.43879600 1.97858000 -0.07208000 C 0.75161800 2.70055600 1.10778200 C 1.80021400 3.61268800 1.12470900 C 2.57545700 3.82210500 -0.02053600 C 2.29236100 3.10543000 -1.18803300 C 1.24559600 2.19192900 -1.21761400 H 0.15540000 2.53155100 1.99909700 H 2.01795700 4.16357700 2.03546600 H 2.89444400 3.26082100 -2.07881800 H 1.02877000 1.63247300 -2.12194900 C 2.43732200 -1.64319200 0.05123900 C 3.14284200 -1.62961100 1.27628100 C 4.52567000 -1.77348500 1.29325300 C 5.23535500 -1.93415600 0.09972000 C 4.54922400 -1.95044000 -1.11817200 C 3.16653500 -1.80837300 -1.14867400 H 2.58957300 -1.50404500 2.20102000 H 5.05442900 -1.75964700 2.24188200 H 5.09613200 -2.07540100 -2.04821300 H 2.63098500 -1.82290600 -2.09220600 O -4.76535200 0.31748400 -0.07603400 C -4.25862400 1.58750100 0.36082600 H -5.05722400 2.30281500 0.15177900 H -4.09647500 1.55040400 1.44736100 C -2.96049900 1.96999200 -0.35221200 H -2.59951700 2.93565200 0.01403400 H -3.16392500 2.07914400 -1.42544700 H 3.39616000 4.53282700 -0.00169800 H 6.31520600 -2.04636100 0.11856100

(8b TS2) Total Energy= -1078.5530141, one negative frequency (-330.0607)

C -2.61461300 -2.94210900 0.03628900 C -2.09318400 -1.64186200 0.00266300 C -2.96577100 -0.53645500 -0.04137000 C -4.35177400 -0.74174600 -0.03077700 C -4.87115700 -2.03881100 -0.00472500 C -3.99896600 -3.12751200 0.02322700 H -1.94000500 -3.79069200 0.06651900 H -5.94767800 -2.17310300 -0.00040100

H -4.40472600 -4.13451900 0.04507500 C -2.38114600 0.80365300 -0.13177000 C -1.06284500 0.92807300 -0.08366700 C -0.67992000 -1.36736600 -0.00050000 C 0.52231800 -1.65515100 0.01270500 C 0.00613100 1.85985000 -0.07299400 C 0.34498500 2.57170300 1.10476100 C 1.41311500 3.45934700 1.11830000 C 2.20127200 3.67352600 -0.02302600 C 1.88168300 2.95357500 -1.18565800 C 0.81700900 2.06371300 -1.21698900 H -0.24458200 2.41284800 2.00244600 H 1.64617900 3.99751300 2.03410700 H 2.48399300 3.09392100 -2.08015900 H 0.59218500 1.51173000 -2.12406100 C 1.92681000 -1.81813500 0.03173900 C 2.63993200 -1.82930000 1.25194700 C 4.01682700 -2.00979700 1.26339200 C 4.74197700 -2.18417600 0.07456300 C 4.03200500 -2.17776100 -1.13521600 C 2.65446100 -1.99961800 -1.16555200 H 2.09627900 -1.69745900 2.18162600 H 4.54355700 -2.01702100 2.21454300 H 4.57023900 -2.31762800 -2.06940700 H 2.12214100 -2.00218100 -2.11113000 O -5.22987500 0.30976500 -0.05901900 C -4.69304100 1.56620200 0.38090000 H -5.47691800 2.29985500 0.17945300 H -4.52608200 1.52054400 1.46644000 C -3.39038300 1.92305500 -0.33702700 H -3.00650700 2.87898200 0.03158200 H -3.59707000 2.04161300 -1.40869900 C 3.34271200 4.66049300 -0.00937900 C 6.24194300 -2.34777800 0.09752300 H 3.74369600 4.79587400 0.99951200 H 4.16166400 4.33507600 -0.65844600 H 3.02089600 5.64757500 -0.36623100 H 6.57179300 -2.89581000 0.98553600 H 6.60019000 -2.88528000 -0.78531800 H 6.74746300 -1.37363300 0.11301000

(8c TS2) Total Energy= -1198.3746367, one negative frequency (-329.2069)

C -2.57617300 -2.94422700 0.03214300 C -2.05882400 -1.64254200 0.00172700 C -2.93424800 -0.53925400 -0.04001600 C -4.31966200 -0.74796500 -0.02975700 C -4.83519900 -2.04683700 -0.00721300 C -3.96020800 -3.13307600 0.01826700 H -1.89957100 -3.79122200 0.06076300 H -5.91128600 -2.18420000 -0.00356100 H -4.36327100 -4.14113100 0.03765500 C -2.35329100 0.80273800 -0.12868400 C -1.03514000 0.92870300 -0.08317900 C -0.64622800 -1.36409000 -0.00066200 C 0.55726200 -1.64564900 0.01397800 C 0.03245700 1.86347600 -0.07519600 C 0.37939300 2.56391000 1.10866200 C 1.44473400 3.45543700 1.13026100 C 2.18707600 3.64452800 -0.03252300 C 1.89474200 2.96591900 -1.21288100 C 0.82790900 2.07661800 -1.22955200 H -0.20490300 2.39760500 2.00780100 H 1.71047700 4.00228400 2.02857700 H 2.50274800 3.14097300 -2.09388100 H 0.58814700 1.53564600 -2.13884700 C 1.96345400 -1.79563300 0.03497000 C 2.67444200 -1.77506500 1.25752100 C 4.05436400 -1.93649300 1.28201000 C 4.73125000 -2.12081900 0.07991600 C 4.06887000 -2.14933400 -1.14399600 C 2.68886100 -1.98844300 -1.16382900 H 2.12833600 -1.62954600 2.18313900 H 4.61131200 -1.92077400 2.21238100 H 4.63658500 -2.29640800 -2.05619500 H 2.15344500 -2.00998200 -2.10685800 O -5.20021500 0.30065500 -0.05521900 C -4.66723900 1.55770000 0.38770300 H -5.45293800 2.28960400 0.18775300 H -4.50035200 1.50982500 1.47308800 C -3.36576200 1.92002200 -0.32971000 H -2.98474300 2.87630600 0.04087800

H -3.57268700 2.04031000 -1.40106900 F 3.22342600 4.50863600 -0.01381400 F 6.07028300 -2.27777800 0.10163300

(8d TS2) Total Energy= -1228.9626887, one negative frequency (-316.6380)

C -3.08306300 -2.99688200 -0.08553300 C -2.54048500 -1.70483800 -0.06297100 C -3.39585900 -0.58480700 -0.03542700 C -4.78474500 -0.77038000 -0.00871100 C -5.32464900 -2.05889500 -0.03745600 C -4.47000700 -3.16092800 -0.08118200 H -2.42143300 -3.85583800 -0.11103500 H -6.40301200 -2.17648300 -0.01928000 H -4.89152300 -4.16150300 -0.10216400 C -2.79333000 0.75034000 -0.07293500 C -1.47201400 0.85335700 -0.04365200 C -1.12281200 -1.45465700 -0.08027400 C 0.07393200 -1.76446300 -0.09964200 C -0.39616500 1.77503900 0.00921200 C -0.08408900 2.47343600 1.20711300 C 0.98545000 3.34799800 1.27002900 C 1.80270200 3.55352900 0.14503000 C 1.52931200 2.86330400 -1.04405000 C 0.45157200 1.98500900 -1.10267400 H -0.70439100 2.31469200 2.08371500 H 1.21717000 3.88924700 2.18170000 H 2.14893100 2.99991000 -1.92238900 H 0.24916800 1.44785300 -2.02360300 C 1.47619600 -1.94296000 -0.10756500 C 2.21833400 -1.93077000 1.09144600 C 3.59753800 -2.11968200 1.09200100 C 4.27291400 -2.32736800 -0.11819000 C 3.55001300 -2.34481300 -1.32289800 C 2.17921700 -2.15828400 -1.31872700 H 1.69914100 -1.76761400 2.02994100 H 4.13334700 -2.10134400 2.03344300 H 4.09221600 -2.50894800 -2.24825800 H 1.62690900 -2.17578800 -2.25249900 O -5.64773200 0.29367200 0.03138000 C -5.08371800 1.52028700 0.51813200

H -5.86056800 2.27345100 0.36738300 H -4.89574300 1.42171300 1.59678600 C -3.79043600 1.89111500 -0.20920400 H -3.38597400 2.82480100 0.19304100 H -4.01689400 2.05989700 -1.27020100 O 2.83050600 4.43512000 0.31478600 O 5.61756400 -2.52143600 -0.23359700 C 3.69328000 4.68238500 -0.78444000 H 4.21245600 3.77034400 -1.10541400 H 3.14953200 5.10425400 -1.63932100 H 4.42776400 5.40859000 -0.43332000 C 6.40210800 -2.51925300 0.94967700 H 7.43041700 -2.69113900 0.62894800 H 6.34286700 -1.55628500 1.47248400 H 6.09975000 -3.31957600 1.63683100

(8e TS2) Total Energy= -1355.1733719, one negative frequency (-386.2060)

C 1.05912900 -2.97467600 0.01555900 C 0.92639600 -1.57998500 0.01241600 C 2.07422000 -0.76875400 0.03980800 C 3.34789500 -1.35163000 0.04529100 C 3.48090800 -2.74273900 0.05788900 C 2.33598600 -3.54090000 0.04835300 H 0.17349800 -3.60012300 -0.00250200 H 4.47529600 -3.17632400 0.06653600 H 2.44182800 -4.62164100 0.05529500 C 1.86690800 0.67982800 0.09169500 C 0.61919900 1.14133500 0.03850600 C -0.35878100 -0.92041000 -0.00597500 C -1.60488000 -0.97038000 -0.02245600 O 4.48113900 -0.58442500 0.04860000 C 4.30428600 0.75468100 -0.43865000 H 5.25861900 1.25466400 -0.25909200 H 4.12637000 0.71619800 -1.52259400 C 3.15160200 1.48080800 0.25787700 H 3.05364000 2.49283300 -0.14367500 H 3.38539800 1.57205300 1.32677100 Si -3.43365900 -1.16235100 -0.02031200 C -3.83540400 -2.85654200 -0.76166800

H -4.91896900 -3.02119000 -0.78460200 H -3.46256500 -2.93770100 -1.78771300 H -3.38584900 -3.66536200 -0.17694100 C -4.05662700 -1.07508700 1.76234700 H -3.84281000 -0.10299100 2.21749400 H -5.14115500 -1.22959300 1.79630900 H -3.58797200 -1.84467000 2.38371500 C -4.25987400 0.18059700 -1.06301800 H -5.34528300 0.02836800 -1.08273800 H -4.07053600 1.18136700 -0.66356200 H -3.90251500 0.15828000 -2.09759800 Si -0.41875200 2.67267600 0.01040300 C -1.30226600 2.78526100 -1.65752000 H -1.89056100 1.88533100 -1.85609300 H -1.97816100 3.64761400 -1.68804000 H -0.58064600 2.89782000 -2.47362100 C 0.65986900 4.22259800 0.22856300 H 0.02758100 5.11863600 0.23887600 H 1.21861600 4.20241700 1.16981800 H 1.37795500 4.33905700 -0.59004300 C -1.66942100 2.60999900 1.42681400 H -2.32602500 3.48739300 1.41004700 H -2.29385700 1.71473100 1.36189200 H -1.16212400 2.58966200 2.39699500

(9a) Total Energy= -999.9640845

C -2.04339800 -3.70341500 0.08504100 C -0.83650300 -2.98265500 0.05185600 C -0.91179900 -1.59452700 0.02151700 C -2.16395900 -0.97280800 0.02501000 C -3.35776500 -1.67953400 0.03137900 C -3.29770600 -3.07637700 0.07073500 H -2.00692800 -4.78864400 0.11160700 H 0.11653400 -3.50245100 0.05401500 H -4.21352900 -3.65798900 0.08282700 C -4.44139000 0.33340300 -0.55291200 H -5.42744200 0.77877900 -0.40788300 H -4.25390800 0.23736100 -1.63102000

C -3.34108900 1.21216500 0.08165200 H -3.29750700 2.17283700 -0.44392500 H -3.61770400 1.43023700 1.12268800 C -2.03712300 0.46603000 0.04000800 O -4.54419300 -0.99208800 0.00909600 C -0.71144200 0.80325700 0.01268100 C 0.08562500 -0.48029600 0.00325800 C 1.39371500 -0.61893800 0.02564900 C -0.12511300 2.15004800 0.00523900 C -0.73246200 3.20243200 0.71705800 C 1.04692100 2.43629500 -0.72014200 C -0.19724500 4.48877800 0.69497300 H -1.61419000 3.00030700 1.31630700 C 1.58362700 3.72166200 -0.73640800 H 1.52776400 1.64717000 -1.28755800 C 0.96405100 4.75559100 -0.03187500 H -0.68236800 5.28167800 1.25736600 H 2.48687100 3.91747800 -1.30730200 H 1.38386500 5.75706400 -0.04608100 C 2.72019300 -0.97973000 0.03854100 C 3.43622300 -1.12269500 1.27241600 C 3.44187300 -1.19662100 -1.18143100 C 4.77722200 -1.46437900 1.27063700 H 2.90655800 -0.95753500 2.20451000 C 4.78340000 -1.53629200 -1.15321200 H 2.91548500 -1.09535400 -2.12480900 C 5.46430000 -1.67378100 0.06544900 H 5.30125000 -1.57008700 2.21625800 H 5.31150800 -1.69959600 -2.08836700 H 6.51635900 -1.94021600 0.07588000

(9b) Total Energy= -1078.605938

C -1.53902400 -4.23252300 0.06036500 C -0.51342600 -3.27144200 0.02550100 C -0.88197300 -1.93063900 0.00764200 C -2.23754600 -1.58878300 0.02375000 C -3.25356800 -2.53367600 0.03143400 C -2.89794600 -3.88606100 0.05892100

H -1.27263500 -5.28543200 0.07801100 H 0.52836800 -3.57668800 0.01716900 H -3.66943000 -4.64886400 0.07166800 C -4.74529200 -0.79403400 -0.53070400 H -5.80206000 -0.56912600 -0.37418800 H -4.55230800 -0.84128400 -1.61120500 C -3.85138300 0.29569600 0.10113800 H -4.01686500 1.24452600 -0.42193200 H -4.16151000 0.44837500 1.14448400 C -2.41876700 -0.15578000 0.04775700 O -4.55952300 -2.11471200 0.02101600 C -1.19411900 0.45479200 0.01584700 C -0.14426200 -0.63040800 -0.00673200 C 1.16503900 -0.48845900 0.00637600 C -0.90470700 1.89394200 0.01538500 C -1.72318700 2.79859900 0.71670900 C 0.18963300 2.42727200 -0.69129300 C -1.46603200 4.16729200 0.70054500 H -2.54973800 2.42127300 1.30984900 C 0.44314700 3.79536200 -0.69900000 H 0.83872400 1.76163400 -1.24955000 C -0.38080600 4.69521500 -0.00933600 H -2.11347200 4.83666500 1.26213100 H 1.29704000 4.17356300 -1.25629800 C 2.52736000 -0.69501900 0.02064600 C 3.25579900 -0.76400400 1.25129100 C 3.27828100 -0.80784800 -1.19328100 C 4.62732100 -0.94142500 1.24991600 H 2.71142000 -0.68127600 2.18600300 C 4.64987700 -0.98364200 -1.16089000 H 2.75118800 -0.76477000 -2.14082300 C 5.36015500 -1.05189200 0.05270400 H 5.15330000 -0.99886300 2.19986500 H 5.19299500 -1.07557100 -2.09842200 C -0.11776400 6.18141700 -0.04929800 H 0.95481900 6.39823200 -0.07355200 H -0.55999600 6.64036200 -0.94280700 H -0.54545500 6.68751700 0.82119800 C 6.85935300 -1.20784100 0.06942100 H 7.36242300 -0.23178700 0.05681900 H 7.19785100 -1.73297000 0.96779800 H 7.21454200 -1.76447900 -0.80323300

(9c) Total Energy= -1198.4270911

C -1.44672300 -4.22610600 0.07156600 C -0.43663700 -3.24832900 0.03343900 C -0.82750900 -1.91429800 0.01008400 C -2.18848600 -1.59494500 0.02329600 C -3.18896400 -2.55581500 0.03435200 C -2.81088000 -3.90225300 0.06799500 H -1.16298100 -5.27427600 0.09364100 H 0.60981700 -3.53709800 0.02698300 H -3.56956000 -4.67763500 0.08360900 C -4.70888700 -0.84347600 -0.53569000 H -5.76927000 -0.63557800 -0.38120400 H -4.51350500 -0.89147300 -1.61557200 C -3.83373700 0.26303000 0.09366700 H -4.01528100 1.20763600 -0.43174600 H -4.14636300 0.41235300 1.13669000 C -2.39393900 -0.16493300 0.04186600 O -4.50104800 -2.15857600 0.02125100 C -1.17988500 0.46540800 0.00923100 C -0.11161100 -0.60097900 -0.00861300 C 1.19490900 -0.43485900 0.00433800 C -0.91340600 1.90958700 0.00829000 C -1.74239100 2.79686400 0.72197700 C 0.16575400 2.45715400 -0.71223500 C -1.51767700 4.17156100 0.71124300 H -2.55804600 2.40229100 1.31805900 C 0.40714500 3.82836100 -0.72733900 H 0.81413800 1.80056100 -1.28109200 C -0.44242900 4.66727800 -0.01589600 H -2.15103100 4.85508000 1.26626000 H 1.23442700 4.25232100 -1.28612300 C 2.55924500 -0.64423100 0.02012200 C 3.28338900 -0.69838300 1.25490000 C 3.30642500 -0.76313000 -1.19624800 C 4.65640000 -0.87176600 1.26700100 H 2.73682000 -0.60336600 2.18659400 C 4.67982200 -0.93520200 -1.17378100 H 2.77766000 -0.72396200 -2.14244700

100

C 5.33955200 -0.98737700 0.05507800 H 5.21168600 -0.91917300 2.19753000 H 5.25230800 -1.03240300 -2.08991600 F -0.21458900 5.99825700 -0.02804200 F 6.67688800 -1.15443900 0.07213900

(9d) Total Energy= -1229.0150273

C 0.08778900 -4.71118100 -0.12043500 C -0.52198000 -3.44680700 -0.03899700 C 0.30444800 -2.32865000 -0.00801900 C 1.69166700 -2.49644200 -0.05639700 C 2.29877200 -3.74257700 -0.10990100 C 1.48031200 -4.87584800 -0.15141700 H -0.53979800 -5.59732600 -0.14910100 H -1.60338200 -3.35698300 -0.00576700 H 1.92548100 -5.86420400 -0.19935600 C 4.32603800 -2.67212300 0.44794000 H 5.39060000 -2.83750100 0.27077300 H 4.14500500 -2.67830600 1.53150400 C 3.87413800 -1.31549000 -0.13701800 H 4.37789600 -0.50521700 0.40294500 H 4.20335200 -1.25353500 -1.18396300 C 2.37610600 -1.22429700 -0.05588700 O 3.66892800 -3.82047600 -0.12816300 C 1.45358300 -0.21576500 0.02084500 C 0.08479100 -0.85055500 0.05263300 C -1.08668100 -0.24515200 0.08224300 C 1.70014100 1.23073900 0.05242900 C 2.77500800 1.80044500 -0.64899400 C 0.88028700 2.10642200 0.79540600 C 3.03998600 3.17045600 -0.61214900 H 3.40499400 1.16675900 -1.26446100 C 1.12823100 3.46983000 0.83754100 H 0.04559500 1.70355100 1.35813100 C 2.21313700 4.01543400 0.13574400 H 3.87715100 3.56355700 -1.17689600 H 0.49768200 4.13723100 1.41589800 C -2.45813500 -0.06833200 0.11067000

101

C -3.20993700 0.11838500 -1.08809800 C -3.17650100 -0.00172800 1.34924100 C -4.57911400 0.34011000 -1.05694500 H -2.69166200 0.08114900 -2.04031400 C -4.53637900 0.21943200 1.37113900 H -2.63229100 -0.13671000 2.27806100 C -5.25637700 0.39382100 0.17214200 H -5.11252800 0.47016800 -1.99112000 H -5.08162100 0.26218300 2.30838200 O 2.37250300 5.36798600 0.24325300 O -6.59399300 0.60740300 0.31548800 C 3.45723600 5.97040100 -0.44339100 H 3.40221100 7.03661700 -0.21876800 H 4.42320200 5.57888900 -0.09895100 H 3.38081800 5.82684500 -1.52901300 C -7.37836300 0.79620000 -0.85331500 H -8.40107100 0.94972800 -0.50679500 H -7.05296600 1.67747800 -1.42016600 H -7.34739200 -0.08403900 -1.50771000

(9e) Total Energy= -1355.2178168

C 1.79619800 -3.56929000 -0.11476500 C 0.60261400 -2.82758500 -0.06766300 C 0.69948000 -1.43996700 -0.02824900 C 1.96267100 -0.84189300 -0.03030800 C 3.14394500 -1.56910300 -0.05908500 C 3.06045000 -2.96497100 -0.10879900 H 1.74029100 -4.65359600 -0.15007400 H -0.35646900 -3.33465700 -0.07064400 H 3.96657700 -3.56105200 -0.13654700 C 4.27516400 0.42519300 0.49131000 H 5.26521300 0.85204700 0.31961000 H 4.10945000 0.34798700 1.57477700 C 3.17807300 1.31343300 -0.13190400 H 3.18608300 2.28460800 0.37038100 H 3.42407400 1.49681400 -1.18714600 C 1.85220200 0.60342100 -0.04132100 O 4.34470400 -0.90969700 -0.05094500

102

C 0.53436600 0.97371000 -0.02118000 C -0.28035900 -0.30402200 -0.00495200 C -1.60210800 -0.41162900 0.01940400 Si -0.25082600 2.68436800 -0.04221100 Si -3.31981800 -1.06297500 0.04767300 C 1.06635800 4.04816100 -0.05598400 H 0.57546700 5.02682300 -0.11099400 H 1.67744600 4.04423300 0.85281600 H 1.73717400 3.97182700 -0.91768600 C -1.32394400 2.91514100 1.50152900 H -0.71938100 2.86298800 2.41340300 H -1.82526400 3.88977200 1.48823200 H -2.09356700 2.14049500 1.57082900 C -1.31723500 2.87643100 -1.59579300 H -0.70860300 2.80338900 -2.50351400 H -2.08532700 2.09902500 -1.64990900 H -1.82001400 3.85034700 -1.60808800 C -4.17034200 -0.45251400 1.62295300 H -4.21854500 0.64052300 1.65560700 H -5.19650100 -0.83408700 1.67608600 H -3.64078000 -0.79155500 2.51898600 C -4.23260100 -0.42006000 -1.47907000 H -5.25840000 -0.80554300 -1.50235900 H -4.28659000 0.67318900 -1.48395900 H -3.73601800 -0.73550100 -2.40221000 C -3.32721800 -2.95942200 0.02767100 H -2.85059800 -3.35312900 -0.87583700 H -2.80333500 -3.37238500 0.89569600 H -4.35728800 -3.33469100 0.05086700

Tetrayne Cascade Intermediates

(11, 12) Total Energy= -1614.3017629

C -1.64132800 -2.31480900 0.32928500 C -0.93806900 -1.09647400 0.32397300 C 0.47633700 -1.09758300 0.51267200 C 1.13336500 -2.33730700 0.69392400

103

C 0.41637300 -3.53177600 0.67981400 C -0.96791500 -3.51889200 0.49961800 H -2.71729800 -2.29496300 0.19578800 H 0.96104600 -4.46033200 0.81005900 H -1.52084400 -4.45318400 0.49617200 C 1.20889200 0.11887700 0.50927900 C 1.82361400 1.16897100 0.52076000 C -1.64203200 0.11926800 0.11025000 C -2.28395500 1.13354300 -0.08738100 C 2.50415200 2.41661500 0.55333300 C 1.80988500 3.57890300 0.94061300 C 2.44645000 4.81428300 0.98267700 C 3.79815100 4.91486500 0.63789400 C 4.50499500 3.78038900 0.25548200 C 3.88308000 2.51816200 0.20506800 H 0.76475400 3.48803200 1.21788800 H 1.89224400 5.69704000 1.28653700 H 5.55395800 3.85108800 -0.01234900 C -3.00391500 2.33905700 -0.30380600 C -4.42369300 2.33470400 -0.43447600 C -5.09488000 3.55791000 -0.61762100 C -4.39418000 4.75719900 -0.68375700 C -3.00026700 4.75983600 -0.57077200 C -2.31539600 3.56473100 -0.38249400 H -6.17549000 3.54663600 -0.71354900 H -2.44915700 5.69341200 -0.62980100 H -1.23373500 3.55740400 -0.29909200 O 2.50166100 -2.39184800 0.82285900 C 3.04775800 -1.98906400 2.10592500 H 4.11862100 -1.85973700 1.89383200 H 2.65403900 -1.00708700 2.38844600 C 2.81412100 -3.00098000 3.16679100 H 2.95163200 -4.05458500 2.94855800 H 2.62203800 -2.70308900 4.19130700 H 4.29979900 5.87724500 0.66878200 H -4.93264600 5.68882700 -0.82810400 C 4.62586500 1.37409400 -0.19275000 C -5.16008300 1.11844800 -0.39395000 C 5.27361200 0.40497400 -0.54105400 C -5.80392900 0.08662300 -0.37933000 C 6.01286900 -0.74282600 -0.94805200 C 5.38854700 -2.00626700 -1.00620400 C 7.37413500 -0.63319700 -1.29677100 C 6.11697600 -3.12491800 -1.40223800 H 4.34148200 -2.09455400 -0.73399900 C 8.09037800 -1.75889100 -1.69235700

104

H 7.85511900 0.33862400 -1.25291300 C 7.46573800 -3.00748600 -1.74667600 H 5.62777800 -4.09378000 -1.44295200 H 9.13871800 -1.66254600 -1.95945200 H 8.02771500 -3.88378000 -2.05621000 C -6.53933200 -1.13405400 -0.36981800 C -7.87277600 -1.16850400 0.08423300 C -5.94246900 -2.32976200 -0.81854900 C -8.58258500 -2.36584200 0.09227500 H -8.33677600 -0.25070200 0.43020200 C -6.66062400 -3.52200700 -0.80760400 H -4.92061800 -2.30407100 -1.18308000 C -7.98094100 -3.54563100 -0.35193900 H -9.60920700 -2.37878400 0.44631900 H -6.18985800 -4.43579800 -1.15820500 H -8.53815100 -4.47760800 -0.34467200

(Int 1) Total Energy= -1614.3554938

C 1.32689500 -1.77624700 -2.34345400 C 0.11689900 -1.18075300 -1.94234000 C -1.09774900 -1.92070400 -1.99289600 C -1.03760400 -3.24373500 -2.48398900 C 0.17274600 -3.82639300 -2.87156500 C 1.35120000 -3.09287800 -2.79497900 H 2.23551900 -1.18641200 -2.29991800 H 0.15582500 -4.84746100 -3.23708400 H 2.28987900 -3.54348100 -3.10261100 C -3.40668700 -3.38378600 -2.60659600 H -4.15218300 -4.18050600 -2.54906100 H -3.53445400 -2.85126300 -3.55991200 C -3.51537400 -2.41817400 -1.43705900 H -4.49252300 -1.92844900 -1.43241600 H -3.42003400 -2.98045000 -0.49940200 C -2.39287100 -1.38205600 -1.52434900 O -2.13939100 -4.04621900 -2.60388300 C -2.61831600 -0.13633000 -1.16499700 C -3.31265200 0.97201100 -0.72645100 C -3.38775700 1.31690900 0.67917400 105

C -3.93648300 1.85585800 -1.66397200 C -4.07443500 2.48101600 1.06224100 C -4.60360300 2.99184500 -1.24625300 H -3.87496800 1.60777800 -2.71859000 C -4.67619800 3.31215800 0.12197600 H -4.12671000 2.72329200 2.11881000 H -5.07504800 3.63876400 -1.98037100 H -5.19951200 4.20594000 0.44654800 C 0.16860200 0.16837800 -1.48939400 C 0.39626300 1.32078600 -1.16562900 C 0.62351500 2.67217900 -0.78944000 C 1.91342000 3.09584100 -0.35258100 C -0.41897200 3.61542200 -0.85759800 C 2.10793000 4.44694800 -0.01050200 C -0.20194100 4.94455400 -0.51082100 H -1.39820500 3.28716300 -1.18792600 C 1.06397400 5.36210800 -0.08849900 H 3.09213500 4.76153900 0.32037900 H -1.02028500 5.65554200 -0.57028700 H 1.23562400 6.39964500 0.18172500 C -2.78494500 0.48688800 1.65461300 C -2.26477200 -0.22692600 2.49353500 C -1.65037800 -1.07254600 3.45858100 C -0.84229100 -2.15291200 3.04744400 C -1.83628800 -0.84757800 4.83805700 C -0.24213000 -2.98009300 3.99168400 H -0.69246600 -2.32468000 1.98666100 C -1.23158100 -1.68101400 5.77408300 H -2.45605700 -0.01663700 5.15885300 C -0.43371000 -2.74905100 5.35630800 H 0.37927600 -3.80760600 3.66218100 H -1.38229800 -1.49677500 6.83378700 H 0.03713400 -3.39658200 6.08995900 C 2.99252200 2.17554500 -0.25046200 C 3.92847600 1.40591700 -0.14224900 C 5.01231500 0.49057400 -0.01246700 C 4.78764500 -0.89951000 -0.08324900 C 6.32630600 0.95790900 0.19155000 C 5.84953900 -1.79016000 0.04456200 H 3.77675900 -1.26401500 -0.23401900 C 7.38136800 0.05906800 0.31795100 H 6.50363600 2.02695700 0.24737500 C 7.14842100 -1.31633500 0.24480300 H 5.66304700 -2.85873100 -0.01035300 H 8.38919600 0.43252100 0.47411600 H 7.97405700 -2.01471400 0.34401500

106

(Int 2) Total Energy= -1614.4028467

C -1.73887100 -1.99465400 -2.92734800 C -1.21419900 -1.95717400 -1.64029600 C -0.03832200 -2.65806000 -1.35349800 C 0.64353300 -3.40864700 -2.30067200 C 0.12226300 -3.46167700 -3.59842000 C -1.05449000 -2.75760900 -3.88990500 H -2.64863200 -1.46341000 -3.18858100 H 0.63104800 -4.04028500 -4.36231600 H -1.44791200 -2.80252600 -4.90135800 C 0.31898700 -2.54030000 0.04258200 C -0.59801600 -1.74887300 0.67328400 C -1.63116700 -1.33611600 -0.34648100 C -2.68900300 -0.57917800 -0.15244500 C -0.66532500 -1.36070600 2.09300900 C 0.42772700 -0.74384200 2.76235500 C 0.31213300 -0.42099700 4.13022200 C -0.86062900 -0.67593000 4.82977900 C -1.94595900 -1.25727600 4.17012700 C -1.84285900 -1.59052500 2.82216800 H 1.15642200 0.04791100 4.62496600 H -2.86882900 -1.45748000 4.70628600 H -2.68187300 -2.05842900 2.31802300 C -3.85232600 0.13537900 -0.10273200 C -5.10182000 -0.53198900 0.13961000 C -6.28788300 0.16904300 0.18501900 C -6.30114700 1.56505900 -0.00317900 C -5.10962700 2.24736900 -0.23134400 C -3.87664000 1.57823900 -0.28071900 H -5.08877500 -1.60833900 0.27508400 H -7.21827100 -0.36187900 0.36354700 H -5.11451700 3.32361200 -0.37046700 O 1.77989400 -4.08188300 -1.94060900 C 2.42898800 -3.57007500 -0.75520700 H 3.21378600 -4.29477300 -0.53072900 H 2.90131100 -2.61149300 -1.00796800

107

C 1.49713500 -3.37481000 0.45953700 H 2.07172800 -2.92954900 1.27592400 H 1.14161100 -4.35594900 0.80389000 H -0.93120700 -0.41605000 5.88158900 H -7.23829100 2.11112900 0.03265500 C 1.63153400 -0.39495800 2.08264500 C 2.67400900 -0.06108200 1.54983900 C -2.67730500 2.29648800 -0.49295500 C -1.64480100 2.92125400 -0.66119100 C -0.43341600 3.64176400 -0.85491100 C -0.45659300 4.97487100 -1.31395800 C 0.81028000 3.03184900 -0.58983200 C 0.73204300 5.67254600 -1.50475500 H -1.41210200 5.44702500 -1.51801700 C 1.99330800 3.73894900 -0.78360200 H 0.83198500 2.01013800 -0.22518900 C 1.95927600 5.05835200 -1.24210900 H 0.70173100 6.69857500 -1.85979900 H 2.94363300 3.25637100 -0.57693200 H 2.88485000 5.60626500 -1.39247800 C 3.88716700 0.31785200 0.90433000 C 5.02143700 0.67751200 1.65989900 C 3.97446200 0.33737300 -0.50377800 C 6.20467500 1.04195000 1.02381400 H 4.95977500 0.66549600 2.74313300 C 5.16303800 0.70367600 -1.13044700 H 3.10236000 0.06906600 -1.09143300 C 6.28138800 1.05631400 -0.37102100 H 7.07093800 1.31609000 1.61874400 H 5.21569000 0.71441300 -2.21507500 H 7.20648400 1.34097200 -0.86310700

(Int 3) Total Energy= -1614.458789

C 2.74919000 -1.50756300 -2.16621800 C 2.60659500 -0.99308600 -0.87675000 C 3.73906900 -0.46159700 -0.23282300 C 4.99589500 -0.42221300 -0.82110900 C 5.14648100 -0.94920300 -2.10687800

108

C 4.02502800 -1.48214000 -2.75559300 H 1.91373500 -1.92898400 -2.71146000 H 6.11941600 -0.93476600 -2.58694100 H 4.14700500 -1.88494600 -3.75687600 C 3.42708300 -0.01075000 1.10241000 C 2.09121000 -0.24717400 1.33044900 C 1.50977200 -0.84602000 0.10483500 C 0.18329700 -1.12607800 -0.00005500 C 1.24374800 -0.00724600 2.48739300 C -0.14578100 -0.27763800 2.38984500 C -0.97414400 -0.02535900 3.49486600 C -0.46027000 0.47326200 4.68430200 C 0.91270100 0.72006400 4.79397300 C 1.74742200 0.47836300 3.71243500 H -2.03653000 -0.23185400 3.41102400 H 1.32923400 1.09403800 5.72478300 H 2.81107500 0.65340200 3.81704800 C -0.41488600 -1.72621000 -1.22978900 C -0.30439200 -3.10204300 -1.45582500 C -0.85359100 -3.69388700 -2.59342800 C -1.52657700 -2.90630000 -3.52958300 C -1.65111100 -1.53685100 -3.32283900 C -1.10507300 -0.92654800 -2.17606500 H 0.22578500 -3.70934400 -0.72856000 H -0.75474000 -4.76414500 -2.74752800 H -2.17243100 -0.91628300 -4.04419600 O 6.05011700 0.11441600 -0.12715200 C 5.65858300 1.06195500 0.88430500 H 6.58188300 1.31713200 1.40818400 H 5.27839600 1.96315100 0.38386500 C 4.59119300 0.54683700 1.87382300 H 4.31263500 1.38169000 2.52665500 H 5.02941700 -0.22886300 2.51812500 H -1.12156400 0.65938700 5.52517000 H -1.95532200 -3.35880400 -4.41867200 C -0.71888800 -0.84474500 1.13418700 C -2.01405200 -1.11593400 1.01678800 C -1.24993600 0.47899500 -1.98835800 C -1.38959700 1.67859900 -1.84276900 C -1.54982200 3.07912200 -1.63389000 C -2.13364700 3.89351600 -2.62483600 C -1.12778000 3.67130200 -0.42594900 C -2.28989200 5.25974800 -2.40998700 H -2.45833300 3.44160300 -3.55644000 C -1.28888600 5.03845300 -0.22098500 H -0.67701300 3.04715900 0.33862000

109

C -1.86936500 5.83708500 -1.20946000 H -2.74073700 5.87671100 -3.18177800 H -0.96004100 5.48288600 0.71380600 H -1.99275900 6.90345300 -1.04545200 C -3.37165800 -1.31510300 1.04201300 C -3.93691800 -2.54911500 1.50787900 C -4.27463700 -0.29934100 0.57962700 C -5.30817900 -2.73540900 1.51498500 H -3.26914100 -3.33060000 1.85470100 C -5.64142200 -0.51440100 0.59909800 H -3.86192900 0.63280700 0.20956000 C -6.17300600 -1.72658300 1.06479000 H -5.71647300 -3.67586300 1.87429200 H -6.30816200 0.26723700 0.24599000 H -7.24687700 -1.88411000 1.07440500

(Int 4) Total Energy= -1614.5084598

C 2.96544000 -2.94459800 0.20839600 C 3.01169400 -1.55327800 0.07387900 C 4.16685100 -0.88740500 0.53528000 C 5.26268600 -1.54350900 1.08138800 C 5.22956400 -2.93668800 1.17587600 C 4.07997800 -3.61060200 0.74476600 H 2.09940300 -3.52158800 -0.08958400 H 6.07468600 -3.47308200 1.59428000 H 4.04577100 -4.69237500 0.83644700 C 4.05131000 0.53916300 0.38345300 C 5.25238400 1.33456800 0.80734400 H 4.98953800 2.31351500 1.22413500 H 5.91282100 1.51994400 -0.05227800 C 6.02493900 0.54175500 1.88281300 H 6.98788500 1.01032500 2.09579900 H 5.43345500 0.51887400 2.80847900 O 6.34122500 -0.81420100 1.51363000 C 2.80849400 0.80735700 -0.14093700 C 2.09552200 -0.46842100 -0.36010900 C 0.78444700 -0.47198100 -0.77646000 C 0.02907600 0.79311200 -0.69678000

110

C 0.79971900 2.04983200 -0.84755900 C 2.19080500 2.05317000 -0.55979000 C 0.21612900 3.22406600 -1.35644100 H -0.82948900 3.22116600 -1.63565800 C 0.95850100 4.38603800 -1.52894600 H 0.48094500 5.27525100 -1.92921900 C 2.31886400 4.39839500 -1.20671600 H 2.90744700 5.30065200 -1.34576200 C 2.92645600 3.23983800 -0.74195200 H 3.99306600 3.23829500 -0.55004100 C -1.31710400 0.73142800 -0.40891800 C -2.02494400 -0.56727500 -0.40697300 C -1.34874600 -1.71524100 -1.06143500 C 0.04747400 -1.65222000 -1.24734500 C 0.67965900 -2.67463100 -1.97909400 H 1.73856700 -2.58998400 -2.19279900 C -0.03939100 -3.76605100 -2.45025300 H 0.46603400 -4.54107400 -3.01858100 C -1.41468700 -3.85316300 -2.20697800 H -1.98208900 -4.70438200 -2.57132000 C -2.06274400 -2.82832800 -1.52823700 H -3.13563800 -2.87209000 -1.37067500 C -2.12997600 1.90234400 0.03448200 C -1.76677800 2.63147800 1.17752200 C -3.22703700 -0.69777500 0.14351800 C -4.43454300 -1.14125800 0.63446500 C -4.54744900 -1.65162800 1.96925000 C -5.62952900 -1.07380400 -0.15459600 C -5.77080100 -2.07337300 2.46083100 H -3.65519700 -1.70355900 2.58399300 C -6.84087000 -1.50120600 0.36221800 H -5.56688100 -0.68276000 -1.16475700 C -6.92622000 -2.00423100 1.66844500 H -5.83291500 -2.46171000 3.47345100 H -7.73348900 -1.44492600 -0.25443100 H -7.88069200 -2.33601100 2.06455900 C -3.30300800 2.26615100 -0.64752500 H -3.59753900 1.71137400 -1.53312500 C -4.07620600 3.34213600 -0.21307900 H -4.97338200 3.61630100 -0.76062700 C -3.70126900 4.06181500 0.92247100 H -4.30631900 4.89618100 1.26490700 C -2.54627100 3.69963300 1.61815900 H -2.25172500 4.24860300 2.50793100 H -0.86858500 2.35298000 1.71925900

111

(Int 5) Total Energy= -1614.5365399

C -2.63733800 -2.97031400 -0.53514000 C -2.86049600 -1.62548000 -0.22732200 C -4.13492400 -1.08799400 -0.52575300 C -5.17446200 -1.83526300 -1.06984300 C -4.95909500 -3.19017300 -1.33473000 C -3.69376600 -3.72954400 -1.07068200 H -1.67720400 -3.44378600 -0.37222700 H -5.75443300 -3.79538900 -1.75641600 H -3.51745400 -4.77681600 -1.29860300 C -4.19874700 0.30453000 -0.21817900 C -5.51829500 0.97326000 -0.46704300 H -5.41392700 2.01187900 -0.80183200 H -6.11867800 0.99629200 0.45473300 C -6.27870000 0.19331800 -1.56060600 H -7.31219200 0.53675100 -1.63774500 H -5.78232300 0.35336500 -2.52741800 O -6.37296300 -1.22766300 -1.33378500 C -2.93913600 0.68596600 0.25706300 C -2.07084800 -0.48060400 0.28133200 C -0.71798700 -0.35070800 0.62765600 C -0.15626500 0.97218800 0.64568300 C -1.03667700 2.10164000 0.90030900 C -2.44690800 1.95694000 0.72507200 C -0.54809500 3.31264600 1.44335400 H 0.51099300 3.40115500 1.65496700 C -1.39657400 4.36296600 1.74919200 H -0.99463900 5.27541700 2.17935400 C -2.77757500 4.23341500 1.53064400 H -3.44783100 5.05208600 1.77596100 C -3.29015800 3.04419200 1.03973900 H -4.36246000 2.93225100 0.92918900 C 1.24016300 1.08076700 0.34511700 C 2.11173200 -0.10803600 0.40312600 C 1.56765400 -1.34489100 0.96522400 C 0.15650100 -1.47004000 1.03114500 C -0.38975900 -2.59749600 1.67372300 H -1.46304400 -2.66253800 1.79981900 112

C 0.42177300 -3.59934300 2.19032400 H -0.02757200 -4.45520100 2.68528400 C 1.81233900 -3.48190600 2.10491400 H 2.45509800 -4.24945800 2.52569200 C 2.37394200 -2.35796200 1.51334000 H 3.45070000 -2.24720000 1.49275500 C 1.98483900 2.13290500 -0.21870400 C 1.60980900 3.35889300 -0.83326200 C 3.36942200 0.18924200 -0.05762400 C 4.54036300 -0.67143800 -0.28393100 C 4.42031000 -1.88072300 -0.99661000 C 5.82671100 -0.27305500 0.12745300 C 5.53793600 -2.66564600 -1.26760400 H 3.44083000 -2.19289400 -1.34375800 C 6.94422100 -1.06131800 -0.14427400 H 5.94896700 0.65360700 0.68115900 C 6.80581900 -2.26187600 -0.84181700 H 5.41955800 -3.59207000 -1.82227100 H 7.92439200 -0.73670500 0.19317200 H 7.67643600 -2.87458000 -1.05552500 C 3.42084300 1.67809700 -0.33747400 H 3.94020300 2.08443800 0.56298700 C 4.18391600 2.26915700 -1.48624200 H 5.13144900 1.81846600 -1.76495700 C 3.74006200 3.40546600 -2.06693000 H 4.32694700 3.88453200 -2.84596300 C 2.46771700 3.98578300 -1.70343700 H 2.15471300 4.90398800 -2.19140000 H 0.61357100 3.75835700 -0.68988900

(13) Total Energy= -1614.5938159

C 3.26860400 -2.68645700 0.79129300 C 3.21418200 -1.39417600 0.26625600 C 4.43200100 -0.67234400 0.19230100 C 5.66446600 -1.19822400 0.56726700 C 5.71743700 -2.51296500 1.04188700 C 4.51947400 -3.22539200 1.15570600 H 2.37983300 -3.28849800 0.93042300

113

H 6.66570500 -2.94756800 1.33884000 H 4.55089700 -4.23556400 1.55350300 C 4.21751100 0.65501200 -0.26742700 C 5.43553900 1.51936600 -0.39676200 H 5.24107100 2.56901800 -0.14860300 H 5.80880200 1.50299200 -1.43183800 C 6.52783900 0.99881500 0.56082000 H 7.48875700 1.47302400 0.35265800 H 6.23853300 1.22862700 1.59510300 O 6.78384000 -0.41889900 0.47449000 C 2.82664400 0.80566700 -0.47355700 C 2.17150900 -0.43968800 -0.18456000 C 0.74754100 -0.52907700 -0.22557800 C 0.01723700 0.69938700 -0.19272400 C 0.64776000 1.90757400 -0.71089600 C 2.06279000 1.95189600 -0.89193500 C -0.12048900 2.98870700 -1.20307100 H -1.20076500 2.93279800 -1.15820600 C 0.47383600 4.09498400 -1.78549500 H -0.14507300 4.90284000 -2.16419600 C 1.87030200 4.15458000 -1.91537900 H 2.33949500 5.01650700 -2.38068100 C 2.64625300 3.09155800 -1.48699700 H 3.71773700 3.11628400 -1.64738300 C -1.32560500 0.64530500 0.32009700 C -2.00383200 -0.56351200 0.40683200 C -1.39546300 -1.79322700 0.01934200 C 0.00079500 -1.77842900 -0.29042000 C 0.57887600 -2.96675100 -0.79224400 H 1.60264700 -2.94620300 -1.14211200 C -0.15050600 -4.13819700 -0.89560000 H 0.31891400 -5.03034500 -1.29944400 C -1.49998000 -4.16900900 -0.50051900 H -2.06783600 -5.09202700 -0.57044300 C -2.11287600 -3.01176800 -0.06230600 H -3.16653600 -3.02111300 0.19259100 C -2.16468700 1.68914100 0.96543600 C -1.90702500 3.01430200 1.33961800 C -3.39753800 -0.37806200 0.98299900 C -4.55937500 -0.75856800 0.06720500 C -5.65067100 -1.47541700 0.57199500 C -4.58078300 -0.36005400 -1.27639400 C -6.74022500 -1.78933200 -0.24416900 H -5.64686200 -1.79373200 1.61184800 C -5.66573900 -0.67334500 -2.09238000 H -3.73931000 0.19392400 -1.68212700

114

C -6.75070300 -1.38915000 -1.57945200 H -7.57680100 -2.34829000 0.16541400 H -5.66444400 -0.35936700 -3.13230100 H -7.59472900 -1.63403800 -2.21744400 C -3.38688200 1.09773100 1.34479500 C -4.36961500 1.82173100 2.00651800 H -5.31446000 1.35384100 2.26916000 C -4.11890800 3.15563400 2.34117400 H -4.87433400 3.73532300 2.86335600 C -2.88865900 3.73611700 2.02241500 H -2.68749600 4.76402800 2.31016000 H -0.95737000 3.48369700 1.11563400 H -3.49330600 -0.97115200 1.90361600

115

APPENDIX C

NMR SPECTRA OF STARTING MATERIALS AND CASCADE PRODUCTS (CH. 2)

Unless otherwise noted, all 1H NMRs were run on 400 MHz and 600 MHz spectrometer in CDCl3 and CD3CN and all 13C NMR were run on 100 MHz and 150 MHz spectrometer in CDCl3 and CD3CN. Proton chemical shifts are given relative to the residual proton signals of the deuterated solvent CDCl3 (7.26 ppm), CD3CN (1.94 ppm). Carbon chemical shifts were internally referenced to the deuterated solvent signals in CDCl3 (77.00 ppm), CD3CN (1.4, 118.7). All J-coupling values are reported in Hertz (Hz).

Figure 46. 1H NMR spectra of 1-(2-bromoethoxy)-2,3-diiodobenzene.

116

Figure 47. 13C NMR spectra of 1-(2-bromoethoxy)-2,3-diiodobenzene.

Figure 48. 1H NMR spectra of 1a.

117

Figure 49. 13C NMR spectra of 1a.

Figure 50. 1H NMR spectra of 1b.

118

Figure 51. 13C NMR spectra of 1b.

Figure 52. 1H NMR spectra of 1c.

119

Figure 53. 13C NMR spectra of 1c.

1 Figure 54. H NMR spectra of 1d.

120

Figure 55. 13C NMR spectra of 1d.

1 Figure 56. H NMR spectra of 1e. 121

Figure 57. 13C NMR spectra of 1e.

1 Figure 58. H NMR spectra of 1f.

122

Figure 59. 13C NMR spectra of 1f.

1 Figure 60. H NMR spectra of 1g.

123

13 Figure 61. C NMR spectra of 1g.

1 Figure 62. H NMR spectra of 3.

124

Figure 63. 13C NMR spectra of 3.

1 Figure 64. H NMR spectra of 11a. 125

13 Figure 65. C NMR spectra of 11.

1 Figure 66. H NMR spectra of 12a. 126

13 Figure 67. C NMR spectra of 12a.

1 Figure 68. H NMR spectra of 11b.

127

13 Figure 69. C NMR spectra of 11b.

1 Figure 70. H NMR spectra of 12b.

128

Figure 71. 13C NMR spectra of 12b.

1 Figure 72. H NMR spectra of 11c. 129

Figure 73. 13C NMR spectra of 11c.

1 Figure 74. H NMR spectra of 12c.

130

Figure 75. 13C NMR spectra of 12c.

1 Figure 76. H NMR spectra of 11d.

131

Figure 77. 13C NMR spectra of 11d.

1 Figure 78. H NMR spectra of 12d. 132

Figure 79. 13C NMR spectra of 12d.

1 Figure 80. H NMR spectra of 2a. 133

13 Figure 81. C NMR spectra of 2a.

Figure 82. COSY NMR spectra of 2a.

134

1 Figure 83. H NMR spectra of 2b.

13 Figure 84. C NMR spectra of 2b.

135

Figure 85. COSY NMR spectra of 2b.

1 Figure 86. H NMR spectra of 2c. 136

Figure 87. 13C NMR spectra of 2c.

Figure 88. COSY NMR spectra of 2c.

137

1 Figure 89. H NMR spectra of 2d.

Figure 90. 13C NMR spectra of 2d.

138

Figure 91. gHSQC NMR spectra of 2b. Important direct C-H couplings are shown with colored circles. Numbers on cascade product correspond to the following C,H couples. 1: (7.25, 114.2 ppm), 2: (6.92, 126.5 ppm), 3: (6.76, 116.5 ppm), 4: (4.30, 67.2 ppm), 5: (2.96, 25.3 ppm), 6: (7.34, 158.9 ppm), 7: (6.96, 113.79 ppm), 8: (3.87, 55.3 ppm), 9: (7.19, 134.1 ppm), 10: (7.53, 159.7 ppm), 11: (7.00, 113.8 ppm), 12: (3.88, 55.3 ppm).

Figure 92. 1H and 13C chemical shifts determined by 2D NMR for compound 2d.

139

Figure 93. HMBC NMR spectra of 2b. a) Full spectrum. b) Aromatic region.

140

The 2D experiments confirmed the products originate from the 6-exo-dig, 5-exo-dig cascade. Results for the cyclization of the p-methoxy substituted enediyne are discussed in more detail below. There is no gHMBC correlation for the vinyl C-H and the aromatic C-H that is para to the oxygen of the OCH2CH2 moiety on top of the molecule. Lack of the correlation implies that a 5- exo-dig cyclization took place in the 2nd step giving an exo cyclic double bond. The product of an endo-dig cyclization would be expected to display this gHMBC correlation. All protons of the p-OMe-substituted rings were identified by their multiplicity and HMBC couplings to the corresponding methoxy peaks (3.87, 55.3) and (3.88, 55.3 ppm) and the adjacent aromatic C-H bonds at (7.53, 159.7) and (7.34, 158.6) ppm respectively. The single HMBC correlation for the vinyl C-H peak (7.19, 134.1 ppm) is observed with two of the methoxy substituted benzene rings (C-H at 7.00, 113.3 ppm) and (C-H at 7.53, 130.3 ppm) . In the tricyclic core, there is a correlation between the C (150.8 ppm) ipso to the oxygen of the –OCH2CH2- moiety and the aromatic C-H meta to that at (6.92, 126.5 ppm). A correlation of the same quaternary 150.8 ppm carbon is observed for the CH2 next to the oxygen at (4.30, 67.2 ppm). A correlation between the CH2 β to the oxygen at (2.96, 25.3 ppm) and the quaternary aromatic carbon ortho to the ipso quaternary carbon at 114.2 ppm shows that an initial 6-exo-dig cyclization took place instead of the alternative 7-endo-dig cyclization because no correlation would be present for these carbons in the 7-endo cyclization product due to the additional bond between these atoms in the latter structure. gCOSY spectrum shows hydrogen correlations in the methoxy-substituted benzene rings and also correlation between CH2’s of the –OCH2CH2- moiety. Protons in the CH2 groups are magnetically identical, hence there was no attack at the terminal aryl group as observed below for the product of cascade transformation of tetraynes.

141

Figure 94. gCOSY spectrum of 2d shows hydrogen correlations in the methoxy-substituted benzene rings and also correlation between CH2’s of the –OCH2CH2- moiety.

142

1 Figure 95. H NMR spectra of 2e.

13 Figure 96. C NMR spectra of 2e.

143

Figure 97. HSQC NMR spectra of 2e.

Figure 98. 1H and 13C chemical shifts determined by 2D NMR for compound 2e.

144

gHSQC shows clear direct carbon-hydrogen couplings. The two methylene signals are seen at 4.30, 67.2 and 2.99, 27.7 ppm. The three aromatic hydrogens at 7.22, 7.07, and 6.73 are coupled to carbons 116.5, 127.3 and 114.2 respectively. The vinyl hydrogen at 6.54 is coupled to carbon 136.7. The TMS hydrogens at 0.34 and 0.30 are coupled to carbons at 1.3 and 0.2 ppm respectively.

Figure 99. HMBC NMR spectra of 2e.

The vinyl hydrogen-carbon is coupled with the other vinyl carbon α to it at 159.7 ppm, the quaternary carbon α to the aromatic hydrogen at the bottom of the molecule at 138.2 ppm, the quaternary vinyl carbon bound to TMS at 131.5 and the TMS hydrogen at 0.34 ppm. There is no visible interaction between methylene hydrogens and carbon and the TMS hydrogen signals as they are on opposite sides of the molecule. The absence of alkyne carbon signals also indicates that the complete cascade has occurred.

145

Presence of OCH2CH2 moiety is supported by coupling between the hydrogens of the two methylene carbons

Figure 100. COSY NMR spectra of 2e.

Figure 101.The stereochemistry of 2e was determined by 1D nOe experiment.

146

E- stereochemistry is likely to originate from the steric interaction of the two TMS groups. E stereochemistry is consistent with nOes between the vinyl hydrogen and a hydrogen on the methyl groups of TMS. The lack of nOe for this vinyl hydrogen and the ortho aromatic hydrogen further confirms the E stereochemistry.

1 Figure 102. H NMR spectra of 2f.

147

Figure 103. 13C NMR spectra of 2f.

Figure 104. COSY NMR spectra of 2f.

148

1 Figure 105. H NMR spectra of 4.

13 Figure 106. C NMR spectra of 4.

149

Figure 107. 1H NMR spectra of 5.

13 Figure 108. C NMR spectra of 5.

150

1 Figure 109. H NMR spectra of 13a.

13 Figure 110. C NMR spectra of 13a.

151

Figure 111. Full HSQC NMR spectra of 13a.

Figure 112. Full HMBC NMR spectra of 13a.

152

Figure 113. HSQC NMR spectra of 13a for aliphatic and aromatic regions.

153

Figure 114. HMBC NMR spectra of 13a for aliphatic and aromatic regions.

154

Figure 115. 1H and 13C chemical shifts determined by 2D NMR for compound 13a.

Absence of triple bond carbon resonances confirms that cascade proceeded fully and utilized all triple bonds in the process. Presence of diastereotopic CH2 groups confirms formation of a chirality center in the molecule. Connectivity in the OCH2CH2CH-moiety is supported by the 2D correlations in the gHSQC spectrum in which two hydrogens at 4.97 and 4.69 ppm are bound to the carbon at 65.2 ppm and another two hydrogens at 3.57 and 1.98 ppm are bound to the carbon at 30.8 ppm. The methine proton at 2.03 ppm correlates with the carbon at 30.8 ppm. The through bond correlation of the gHMBC for the OCH2CH2CH-moiety can be seen above in the expanded aliphatic spectrum. For the bottom part of the ribbon, 2D correlations readily identify all carbons in the free standing and the fused tolyl groups. The CH singlet at 5.28 ppm on the bottom part of the ribbon displays gHMBC correlations with carbons 135.8 in the ipso position of the free tolyl and 129.7 ppm carbon of the lone CH on the fused tolyl ring between the cyclopentadiene ring and methyl substituent. The 5.28 ppm singlet also confirms the cyclization and aromatization took place. This is also consistent with the presence of only one set of characteristic doublets of a para substituted aromatic rings. Interior carbons can be identified by comparing gHMBC with gHSQC. Presence of gHSQC cross-peaks which are not present in the gHMBC spectrum, locates the interior quaternary carbons in the aromatic region. This can easily be traced starting from the ipso carbon connected to the oxygen at ~153 ppm. All ortho aromatic hydrogens in the central ribbon can be seen in the region of 8-10 ppm in the proton NMR and 120 to 130 ppm in the carbon NMR which is typical of fused benzene rings. By identifying these outlying CH bonds along the perimeter of the structure, one can start to map the connections of the interior carbons. These can be easily identified due to the proton chemical shifts on some of the carbons being quite deshielded. Ortho proton and carbon shifts being the most deshielded with shifts at 9.08, 128.5 and 8.50, 124.4 on the side with the fused tolyl ring and 9.02, 128.9 and 7.91, 123.4. Correlations with these signals can be seen with the central carbons of the ribbon but direct correlations are difficult to determine due to the signals being very close to each other.

155

Figure 116. 1H NMR spectra of 13a2.

13 Figure 117. C NMR spectra of 13a2.

156

Figure 118. 1H NMR spectra of 13b.

13 Figure 119. C NMR spectra of 13b. 157

Figure 120. Full HSQC NMR spectra of 13b.

Figure 121. Full HMBC NMR spectra of 13b.

158

Figure 122. HSQC NMR spectra of 13b aliphatic region.

Figure 123. HSQC NMR spectra of 13b aromatic region. 159

Figure 124. HMBC NMR spectra of 13b aliphatic region.

Figure 125. HMBC NMR spectra of 13b aromatic region. 160

Figure 126. 1H NMR spectra of 13c.

13 Figure 127. C NMR spectra of 13c.

161

Figure 128. Full HSQC NMR spectra of 13c.

Figure 129. Full HMBC NMR spectra of 13c.

162

Figure 130. HSQC NMR spectra of 13c aliphatic region.

Figure 131. HSQC NMR spectra of 13c aromatic region.

163

Figure 132. HMBC NMR spectra of 13c aliphatic and aromatic regions.

164

APPENDIX D

EXPERIMENTAL DETAILS FOR GOLD CATALYZED CASCADE AND OPTIMIZED COORDINATES OF 21 (CH. 4)

Optimized coordinates for 21

Total Energy= -1268.6420844

C 6.17454300 -0.93882300 0.34806100 C 5.27150300 -1.93010000 -0.02980400 C 3.93825300 -1.55783100 -0.12350100 C 3.45269600 -0.25066000 0.09182400 C 4.38613400 0.71438900 0.51413900 C 5.72810600 0.36099900 0.63353000 H 7.22851000 -1.18093700 0.44241700 H 5.57699800 -2.95300100 -0.21996200 H 4.07449100 1.72011800 0.76410800 H 6.44325300 1.10953000 0.96083800 C 2.00039300 -0.34509500 -0.09709400 C 1.76420000 -1.69101400 -0.30271900 O 2.91381500 -2.43219600 -0.37880100 C 0.49523700 -2.31419300 -0.23400600 C 0.86533700 0.55174200 -0.04241400 C -0.44262700 -0.01048200 0.09718600 C -0.61202000 -1.47154100 0.09433700 C -1.81202700 -2.14633200 0.43771000 H -2.66271200 -1.58639300 0.78934000 C 0.36001000 -3.71722700 -0.33310100 H 1.23260600 -4.30532300 -0.59551800 C -0.84955700 -4.31924900 -0.05975000 H -0.95631800 -5.39737300 -0.13188400 C -1.93013400 -3.52261500 0.35711900 H -2.87232300 -3.98836500 0.63051700 C 1.03177600 1.98613400 -0.15742500 C -1.56203100 0.90518100 0.24956800 C -0.05780300 2.83801000 0.17731700 C -1.33142700 2.25284200 0.39141600 H -2.18022500 2.91481300 0.53698700 C 2.20090100 2.59968900 -0.67505800

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H 2.98993900 1.98112500 -1.07877900 C 2.33048600 3.97370900 -0.72933300 H 3.23456800 4.41155500 -1.14224400 C 0.10642600 4.24596800 0.15025000 H -0.73400900 4.87244400 0.43719900 C 1.28879200 4.80990300 -0.27608200 H 1.40424200 5.88928500 -0.30514800 C -3.01204400 0.54032500 0.15920200 C -3.55975900 0.07852900 -1.04984700 C -3.88297600 0.76678700 1.23185500 C -4.92415600 -0.16318700 -1.16778300 H -2.90513600 -0.09298700 -1.89919800 C -5.25213000 0.51836000 1.10837500 H -3.48233300 1.12780700 2.17482200 C -5.79821800 0.04918200 -0.08996600 H -5.32164800 -0.51865500 -2.11562100 H -5.90415600 0.69383300 1.96048700 C -7.27880000 -0.21259800 -0.23275700 H -7.80177200 -0.07966400 0.71821000 H -7.73573400 0.46768600 -0.96124700 H -7.47327700 -1.23274100 -0.58240000

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Experimental

A) Synthesis

THF was obtained from a SPS-4 Solvent Purification System. Hexanes for column chromatography and preparatory thin layer chromatography were distilled prior to use. All other solvents were used as purchased. Column Chromatography was performed using silica gel (60 Å) and preparatory thin layer chromatography was performed using a 1000 m glass backed plate containing UV dye. Unless otherwise noted, all 1H NMRs were run on 400 MHz and 600 13 MHz spectrometer in CDCl3 and CD3CN and all C NMR were run on 100 MHz and 150 MHz spectrometer in CDCl3 and CD3CN. Proton chemical shifts are given relative to the residual proton signal of the deuterated solvent CDCl3 (7.26 ppm) or CD3CN (1.94 ppm). Carbon chemical shifts were internally referenced to the deuterated solvent signals in CDCl3 (77.00 ppm) or CD3CN (1.4, 118.7). All J-coupling values are reported in Hertz (Hz). UV/Vis data was collected on a Perkin Elmer Lambda 950. All high resolution mass spectrometer data were collected on a JEOL JMS 600 double focusing spectrometer.

General Procedure for Sonogashira cross coupling of aryl iodides with different substituted acetylenes (14): A suspension of 2-bromoiodobenzene (3.5 mmol), PdCl2(PPh3)2 (0.18 mmol), Cu(I) iodide (0.18 mmol) in 18 mL of triethylamine was degassed three times with freeze/pump/thaw technique in a flame-dried round bottom flask. 1.1 Equiv. of alkyne (3.89 mmol) was added using a syringe to the thawed solution under argon. The reaction was allowed to react for 8 hours and monitored by TLC. After total consumption of the aryl iodide, the reaction mixture was filtered through celite and extracted with methylene chloride (3 × 30 mL). The organic layer was washed with a saturated solution of ammonium chloride (2 × 30 mL), water (2 × 30 mL) and dried over anhydrous Na2SO4. Solvent was removed in vacuo. The reaction mixture was purified by flash chromatography on silica gel, (eluent: hexane/EtOAc) on silica gel to afford compound 14.

General Procedure for Sonogashira cross coupling of aryl bromides with ethynyltrimethylsilane (15): A suspension of aryl bromide (4.5 mmol), PdCl2(PhCN)2 (0.23 mmol), Cu(I) iodide (0.23 mmol) in 20 mL of triethylamine was degassed three times with freeze/pump/thaw technique in a flame dried round bottom flask. Once reaction mixture was completely thawed and the atmosphere replaced with argon, tri-tert-butylphosphine (0.45 mmol) in a 10% solution of toluene was added, immediately followed by 1.2 equiv. of ethynyltrimethylsilane (5.4 mmol) using a syringe. The reaction was allowed to react for 8 hours and monitored by TLC. After total consumption of the aryl bromide, the reaction mixture was filtered through celite and extracted with methylene chloride (3 × 30 mL). The organic layer was washed with a saturated solution of ammonium chloride (2 × 30 mL), water (2 × 30 mL) and dried over anhydrous Na2SO4. Solvent was removed in vacuo. The reaction mixture was purified by flash chromatography (eluent: hexane/EtOAc) on silica gel to afford compound 15.

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General Procedure for deprotection of TMS protecting groups (16): To a solution of enediyne 15a (3.8 mmol), in 1:1 mixture of MeOH/THF (50 mL) was added K2CO3 (0.54 mmol). The solution was stirred at room temperature for 8 h under argon. Water was added to quench the reaction and an aqueous work up was performed. The reaction mixture was purified by flash chromatography (eluent: hexane/EtOAc) on silica gel to afford compound 16.

General procedure for Sonogashira/ Metal-assisted cascade reaction (17) and (18): To a solution of 2-iodophenol (1.7 mmol), and 1.1 equiv. of enediyne 16 (1.8 mmol) in 16 mL of o-xylene was added 2 equiv. of triethylamine (3.4 mmol) in a 40 mL glass pressure tube. The solution was degassed by bubbling argon through the solution for 20 minutes. To this mixture PdCl2(PPh3)2(83.0 mol) was added and allowed to stir at room temperature for 1 h. To this reaction mixture was added 10% loading of ClAuPPh3 (0.17 mmol) and AgOTf (0.17 mmol). The pressure tube was then sealed and allowed to react for an additional 7-8 h in a 150°C oil bath. At the completion of the reaction, the mixture was cooled to room temperature and filtered through celite. Solvent was then removed in vacuo. The reaction mixture was purified by preparatory thin layer chromatography (eluent: 20% ethyl acetate/ hexane) to afford products 17 and 18, which were extracted off the silica gel using CH2Cl2.

General procedure for metal-assisted electrophilic ring closing step of (17) and (20): A solution of benzofuran (0.15 mmol) in 1.5 mL of o-xylene in a 40 mL glass pressure tube was degassed by bubbling argon through the solution for 20 minutes. To this solution was added ClAuPPh3 (15 mol) and AgOTf (15 mol). The flask was sealed and stirred at 150°C in an oil bath for 8 h. At completion of the reaction, the mixture was passed through a pad of celite and the solvent was removed in vacuo. The reaction mixture was purified by preparatory thin layer chromatography (eluent: 20% ethyl acetate/ hexane) to afford 18 and 21, which were extracted off the silica gel using CH2Cl2.

3-((2-ethynylphenyl)ethynyl)thiophene (16a):

S Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 16a (354 mg, 85% yield) as a oil. Rf=0.7 (10% ethyl acetate in 1 hexanes); H NMR (600 MHz, CD3CN): δ 7.67 (s, 1H), 7.56 (t, J= 7.4 Hz, 2H), 7.46 (s, 1H), 7.40 (t, J= 7.1 Hz, 1H), 7.36 (t, J= 7.4 Hz, 1H), 7.23 (d, J= 13 4.5 Hz, 1H), 3.70 (s, 1H) ; C NMR (150 MHz, CD3CN): δ 133.6, 132.8, 130.7, 130.0, 129.4, 127.5, 126.8, 125.2, 122.7, 89.5, 88.1, 83.1, 82.8; HRMS (EI): calcd for C14H8S [M]+ 208.0347, found 208.0343.

1-ethynyl-2-(phenylethynyl)benzene (16b):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 16b (221 mg, 94% yield) as a light yellow oil. Rf=0.7 (10% ethyl 1 acetate in hexanes); H NMR (600 MHz, CDCl3): δ 7.58 (m, 2H), 7.55 (d, J= 7.9 Hz, 2H), 7.36 (m, 3H), 7.33 (dd, J= 7.6, 1.3 Hz, 1H), 7.29 (td, J= 7.6, 1.3

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13 Hz, 1H), 3.37 (s, 1H) ; C NMR (150 MHz, CDCl3): δ 132.6, 131.8, 128.5, 128.48, 128.3, 127.9, 126.3, 124.6, 123.2, 93.5, 87.8, 82.2, 81.1; HRMS (EI): calcd for C16H10 [M]+ 202.07825, found 202.07756. 1-ethynyl-2-(p-tolylethynyl)benzene (16c):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 16c (867 mg, 93% yield) as a light yellow oil. Rf=0.7 (10% 1 ethyl acetate in hexanes); H NMR (400 MHz, CDCl3): δ 7.55 (dd, J= 7.7, 2.2 Hz, 2H), 7.50 (dd, J= 8.0, 1.6 Hz, 2H), 7.34 (t, J= 7.6 Hz, 1H), 7.28 (t, J= 7.5 Hz, 1H), 7.18 (d, J= 8.0 Hz, 2H), 3.39 (s, 1H), 2.39 (s, 3H) ; 13C NMR (100 MHz, CDCl3): δ 138.6, 132.5, 131.62, 131.6, 129.0, 128.5, 127.7, 126.4, 124.4, 120.0, 93.8, 87.2, 82.2, 81.0, 21.5; HRMS (EI): calcd for C17H12 [M]+ 216.09390, found 216.09386.

1-ethynyl-2-((4-fluorophenyl)ethynyl)benzene (16d):

F Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 16d (1.44 g, 95% yield) as a light yellow solid. Rf=0.8 (10% 1 ethyl acetate in hexanes); H NMR (600 MHz, CD3CN): δ 7.61 (dd, J= 8.9, 5.4 Hz, 2H), 7.59 (dd, J= 7.8, 1.2 Hz, 2H), 7.44 (td, J= 7.5, 1.5 Hz, 1H), 7.40 (td, J= 7.5, 1.5 Hz, 1H), 7.19 (tt, J= 8.9, 2.3 Hz, 2H), 3.72 (s, 13 1H) ; C NMR (150 MHz, CD3CN): δ 164.2 (247.5 Hz), 135.1 (d, J= 8.8 Hz), 134.0, 133.1, 130.4, 130.0, 127.0, 125.7, 120.5 (d, J= 3.2 Hz), 117.3 (d, J= 22.0 Hz), 93.4, 88.7, 83.5, 83.1; HRMS (EI): calcd for C16H9F [M]+ 220.0688, found 220.0679.

1-ethynyl-2-((4-methoxyphenyl)ethynyl)benzene (16e):

O Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 16e (650 mg, 90% yield) as a light red solid. Rf=0.6 (10% ethyl 1 acetate in hexanes); H NMR (400 MHz, CDCl3): δ 7.53 (m, 4H), 7.32 (td, J= 7.6, 1.5 Hz, 1H), 7.26 (td, J= 7.6, 1.4 Hz, 1H), 6.89 (dd, J= 8.9, 4.6 Hz, 13 2H), 3.82 (s, 3H), 3.38 (s, 1H) ; C NMR (100 MHz, CDCl3): δ 159.8, 133.2, 132.5, 131.5, 128.5, 127.5, 126.6, 124.3, 115.2, 113.9, 93.7, 86.6, 82.3, 80.9, 55.2; HRMS (EI): calcd for C17H12O [M]+ 232.0888, found 232.0879.

4-((2-ethynylphenyl)ethynyl)benzonitrile (16f):

CN Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 16f (386 mg, 89% yield) as a light yellow oil. Rf=0.5 (10% ethyl 1 acetate in hexanes); H NMR (400 MHz, CDCl3): δ 7.63 (d, J= 1.5 Hz, 2H), 7.62 (d, J= 1.8 Hz, 2H), 7.54 (m, 2H), 7.34 (m, 2H), 3.39 (s, 1H) ; 13C NMR

169

(100 MHz, CDCl3): δ 132.7, 132.1, 132.0, 131.9, 128.7, 128.6, 128.0, 125.1, 124.9, 118.5, 111.6, 92.0, 91.5, 81.8, 81.5; HRMS (EI): calcd for C17H9N [M]+ 227.07350, found 227.07255.

3-((2-ethynylphenyl)ethynyl)pyridine (16g):

N Chromatographic purification (25% ethyl acetate in hexanes) afforded compound 16g (669 mg, 84% yield) as a light brown solid. Rf=0.6 (10% ethyl 1 acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.79 (s, 1H), 8.54 (d, J= 3.8 Hz, 1H), 7.82 (dd, J= 7.9, 1.5 Hz, 1H), 7.53 (d, J= 7.5 Hz, 2H), 7.31 (m, 13 2H), 7.27 (m, 1H), 3.38 (s, 1H) ; C NMR (150 MHz, CDCl3): δ 152.3, 148.6, 138.5, 132.6, 131.8, 128.5, 128.4, 125.4, 124.7, 123.0, 120.3, 91.0, 89.9, 81.9, 81.4; HRMS (EI): calcd for C15H10N [M]+ 204.08132, found 204.08095.

1-ethynyl-2-(hex-1-yn-1-yl)benzene (16h):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 16h (475 mg, 93% yield) as a oil. Rf=0.75 (10% ethyl acetate in 1 hexanes); H NMR (600 MHz, CD3CN): δ 7.48 (d, J= 6.7 Hz, 1H), 7.40 (d, J= 7.7 Hz, 1H), 7.31 (t, J= 7.6 Hz, 1H), 7.27 (td, J= 7.5, 1.1 Hz, 1H), 3.57 (s, 1H), 2.45 (t, J= 6.9 Hz, 2H), 1.57 (p, J= 6.9 Hz, 2H), 1.51 (p, J= 7.1 Hz, 2H), 0.94 13 (t, J= 7.3 Hz, 3H) ; C NMR (150 MHz, CD3CN): δ 133.5, 132.9, 129.8, 128.6, 127.8, 125.2, 96.0, 83.1, 82.4, 79.9, 31.5, 22.7, 19.7, 14.0; HRMS (EI): calcd for C14H14 [M]+ 182.10955, found 182.10943.

1-ethynyl-2-((4-methoxyphenyl)ethynyl)-4-methylbenzene (16i):

O Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 16i (905 mg, 94% yield) as a light yellow solid. Rf=0.8 (10% 1 ethyl acetate in hexanes); H NMR (400 MHz, CDCl3): δ 7.52 (d, J= 8.8 Hz, 2H), 7.42 (d, J= 7.9 Hz, 1H), 7.35 (bs, 1H), 7.07 (dd, J= 6.3, 0.6 Hz, 13 1H), 6.88 (d, J= 8.9 Hz, 2H), 3.82 (s, 3H), 2.34 (s, 3H) ; C NMR (100 MHz, CDCl3): δ 159.7, 138.7, 133.2, 132.3, 132.0, 128.6, 126.3, 121.3, 115.2, 113.9, 93.2, 86.7, 82.4, 80.2, 55.2, 21.2; HRMS (EI): calcd for C18H14O [M]+ 246.1045, found 246.1026.

1-((4-chlorophenyl)ethynyl)-2-ethynylbenzene(16j):

Cl Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 16j (540 mg, 84% yield) as a clear solid. Rf=0.7 (10% ethyl 1 acetate in hexanes); H NMR (600 MHz, CDCl3): δ 7.53 (t, J= 7.8 Hz, 2H), 7.49 (d, J= 8.5 Hz, 2H), 7.33 (d, J= 8.5 Hz, 3H), 7.30 (td, J= 7.5, 1.4 Hz, 13 1H), 3.37 (s, 1H) ; C NMR (150 MHz, CDCl3): δ 134.5, 132.9, 132.6,

170

131.7, 128.7, 128.6, 128.1, 125.9, 124.6, 121.6, 92.3, 88.8, 82.1, 81.2; HRMS (EI): calcd for C16H9Cl [M]+ 236.0393, found 236.0410.

2-(2-(thiophen-3-ylethynyl)phenyl)benzofuran (17a):

S Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 17a (284 mg, 57% yield) as a light orange solid. Rf=0.8 (10% 1 ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.09 (dd, J= 8.0, 1.1 Hz, 1H), 7.78 (d, J= 1.0 Hz, 1H), 7.67 (dd, J= 7.7, 1.3 Hz, 1H), 7.65 (dt, J= 8.9, 0.7 Hz, 1H), 7.62 (dd, J= 3.0, 1.1 Hz, 1H), 7.56 (dd, J= 8.3, 0.8 O Hz, 1H), 7.46 (td, J= 7.9, 1.3 Hz, 1H), 7.38 (dd, J= 5.1, 3.0 Hz, 1H), 7.34 (tdd, J= 7.7, 3.1, 1.3 Hz, 2H), 7.29 (dd, J= 5.1, 1.2 Hz, 1H), 7.27 (td, J= 7.6, 1.0 Hz, 1H) ; 13C NMR (150 MHz, CDCl3): δ 154.3, 153.9, 133.8, 131.3, 129.6, 129.2, 128.8, 128.6, 127.8, 126.7, 125.7, 124.7, 122.9, 122.3, 121.3, 119.6, 111.0, 105.8, 89.8, 88.9; HRMS (EI): calcd for C20H12OS [M]+ 300.0609, found 300.0601.

2-(2-(phenylethynyl)phenyl)benzofuran (17b):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 17b (52 mg, 65% yield) as a light yellow oil. Rf=0.7 (10% ethyl 1 acetate in hexanes); H NMR (400 MHz, CDCl3): δ 8.08 (dd, J= 8.0, 1.0 Hz, 1H), 7.79 (s, 1H), 7.69 (dd, J= 6.4, 0.9 Hz, 1H), 7.62 (m, 3H), 7.56 (dd, J= 8.1, 0.6 Hz, 1H), 7.47 (td, J= 8.0, 1.4 Hz, 1H), 7.42 (m, 3H), 7.34 (m, 2H), O 13 7.26 (td, J= 7.2, 1.0 Hz, 1H) ; C NMR (100 MHz, CDCl3): δ 154.3, 153.8, 133.9, 131.5, 131.4, 129.2, 128.6, 128.58, 128.5, 127.8, 126.6, 124.7, 123.2, 122.9, 121.4, 119.6, 111.1, 105.9, 94.5, 89.4; HRMS (EI): calcd for C22H14O [M]+ 294.1045, found 294.1032.

2-(2-(p-tolylethynyl)phenyl)benzofuran (17c):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 17c (61 mg, 62% yield) as a clear oil. Rf=0.7 (10% ethyl acetate 1 in hexanes); H NMR (400 MHz, CDCl3): δ 8.10 (dd, J= 8.0, 1.0 Hz, 1H), 7.82 (d, J= 1.0 Hz, 1H), 7.69 (dd, J= 6.84, 0.4 Hz, 1H), 7.65 (dq, J= 9.0, 0.7 Hz, 1H), 7.57 (dq, J= 8.1, 0.9 Hz, 1H), 7.52 (dd, J= 8.1, 4.6 Hz, 2H), 7.46 (td, J= 8.0, 1.4 Hz, 1H), 7.34 (m, 2H), 7.28 (dd, J= 8.1, 1.1 Hz, 1H), 7.24 O 13 (m, 2H), 2.42 (s, 3H) ; C NMR (100 MHz, CDCl3): δ 154.2, 153.9, 138.8, 133.8, 131.4, 131.2, 129.3, 129.25, 128.4, 127.7, 126.6, 124.6, 122.8, 121.3, 120.1, 119.8, 111.0, 105.8, 94.7, 88.7, 21.5; HRMS (EI): calcd for C23H16O [M]+ 308.12012, found 308.12076.

171

2-(2-((4-fluorophenyl)ethynyl)phenyl)benzofuran (17d):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 17d (40 mg, 47% yield) as a light yellow solid. Rf=0.8 (10% ethyl 1 acetate in hexanes); H NMR (400 MHz, CDCl3): δ 8.06 (dd, J= 8.0, 1.0 Hz, 1H), 7.71 (d, J= 0.9 Hz, 1H), 7.66 (dd, J= 6.3, 0.8 Hz, 1H), 7.63 (ddd, J= 7.6, 1.3, 0.7 Hz, 1H), 7.58 (d, J= 5.3 Hz, 1H), 7.56 (m, 2H), 7.47 (td, J= 7.4, 1.4 O Hz, 1H), 7.33 (m, 2H), 7.26 (td, J= 4.1, 1.0 Hz, 1H), 7.11 (t, J= 8.6 Hz, 2H) ; 13 C NMR (150 MHz, CDCl3): δ 162.7 (J= 244.5 Hz), 154.3, 153.9, 133.9, 133.4 (J= 7.8 Hz), 131.4, 129.2, 128.7, 127.8, 126.8, 124.8, 122.9, 121.3, 119.5, 119.3, 115.9 (J= 22.1 Hz), 111.1, 105.8, 93.3, 89.0; HRMS (EI): calcd for C22H13OF [M]+ 312.0950, found 312.0947.

2-(2-((4-methoxyphenyl)ethynyl)phenyl)benzofuran (17e):

O Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 17e (66 mg, 56% yield) as a light yellow solid. Rf=0.7 (10% 1 ethyl acetate in hexanes); H NMR (400 MHz, CDCl3): δ 8.07 (dd, J= 8.0, 0.9 Hz, 1H), 7.79 (d, J= 0.9 Hz, 1H), 7.65 (m, 2H), 7.54 (dd, J= 8.9, 0.6 Hz, 3H), 7.44 (td, J= 7.4, 1.4 Hz, 1H), 7.33 (tt, J= 8.8, 1.4 Hz, 2H), 7.26 (td, J= 7.7, 1.1 Hz, 1H), 6.94 (d, J= 8.8 Hz, 2H), 3.86 (s, 3H) ; 13C NMR (150 O MHz, CDCl3): δ 159.9, 154.3, 154.1, 133.7, 133.0, 131.2, 129.3, 128.3, 127.8, 126.6, 124.6, 122.8, 121.3, 120.0, 115.4, 114.2, 111.0, 105.8, 94.6, 88.2, 55.4; HRMS (EI): calcd for C23H16O2 [M]+ 324.11503, found 324.11464.

4-((2-(benzofuran-2-yl)phenyl)ethynyl)benzonitrile (17f):

NC Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 17f (122 mg, 63% yield) as a light yellow solid. Rf=0.7 (10% 1 ethyl acetate in hexanes); H NMR (400 MHz, CDCl3): δ 8.05 (dd, J= 8.0, 0.9 Hz, 1H), 7.68 (m, 1H), 7.65 (dd, J= 11.6, 7.2 Hz, 4H), 7.62 (m, 2H), 7.55 (dd, J= 8.1, 0.8 Hz, 1H), 7.50 (td, J= 15.5, 1.3 Hz, 1H), 7.37 (m, 1H), 7.34 13 O (m, 1H), 7.27 (td, J= 7.6, 1.0 Hz, 1H) ; C NMR (100 MHz, CDCl3): δ 154.3, 153.6, 134.0, 132.1, 131.9, 131.7, 129.4, 128.9, 128.0, 127.9, 126.9, 124.9, 123.0, 121.3, 118.5, 118.4, 111.7, 111.1, 105.8, 93.4, 92.3; HRMS (EI): calcd for C23H13ON [M]+ 319.09972, found 319.09984.

3-((2-(benzofuran-2-yl)phenyl)ethynyl)pyridine (17g):

N Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 17g (52 mg, 54% yield) as a light red oil. Rf=0.4 (10% ethyl 1 acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.80 (bs, 1H), 8.49 (bs, 1H), 7.83 (d, J= 7.7 Hz, 1H), 7.61 (m, 1H), 7.60 (d, J= 1.5 Hz, 1H), 7.58 (d, O J= 1.3 Hz, 1H), 7.57 (m,1H), 7.39 (td, J= 7.6, 1.4 Hz, 2H), 7.35 (td, J= 7.6, 172

13 1.4 Hz, 2H), 7.21 (m, 1H) ; C NMR (150 MHz, CD3CN): δ 154.3, 153.6, 151.9, 149.2, 138.4, 134.1, 131.2, 129.5, 129.0, 128.5, 126.9, 125.2, 123.5, 123.2, 121.7, 119.9, 118.8, 111.0, 105.9, 91.7, 91.0; HRMS (EI): calcd for C17H9N [M]+ 295.33254, found 295.33146.

2-(2-(hex-1-yn-1-yl)phenyl)benzofuran (17h):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 17h (366 mg, 68% yield) as a yellow oil. Rf=0.8 (10% ethyl 1 acetate in hexanes); H NMR (400 MHz, CDCl3): δ 8.02 (dd, J= 8.0, 1.1 Hz, 1H), 7.73 (d, J= 0.9 Hz, 1H), 7.61 (dq, J= 7.6, 0.8 Hz, 1H), 7.53 (m, 2H), 7.39 (td, J= 7.5, 1.4 Hz, 1H), 7.30 (m, 2H), 7.24 (td, J= 7.3, 1.3 Hz, 1H), 2.57 (t, J= 7.0 Hz, 2H), 1.69 (quin, J= 8.2 Hz, 2H), 1.55 (sex, J= 7.8 Hz, 13 O 2H), 0.98 (t, J= 7.3 Hz, 3H) ; C NMR (150 MHz, CDCl3): δ 154.1, 154.07, 134.1, 131.1, 129.2, 127.8, 127.6, 126.4, 124.5, 122.7, 121.2, 120.5, 111.0, 105.4, 96.1, 80.5, 30.6, 22.1, 19.5, 13.6; HRMS (EI): calcd for C20H18O [M]+ 274.1358, found 274.1367.

2-(2-((4-methoxyphenyl)ethynyl)-4-methylphenyl)benzofuran (17i):

O Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 17i (387 mg, 50% yield) as a yellow solid. Rf=0.8 (10% ethyl 1 acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.00 (d, J= 8.1 Hz, 1H), 7.77 (d, J= 0.8 Hz, 1H), 7.66 (dt, J= 8.8, 0.7 Hz, 1H), 7.57 (d, J= 8.7 Hz, 3H), 7.51 (m, 1H), 7.34 (td, J= 8.4, 1.4 Hz, 1H), 7.27 (m, 2H), 6.96 (d, 13 O J= 8.8 Hz, 2H), 3.86 (s, 3H), 2.41 (s, 3H) ; C NMR (150 MHz, CDCl3): δ 159.8, 154.2, 154.1, 137.8, 134.1, 132.9, 129.4, 129.3, 128.5, 126.5, 124.3, 122.7, 121.1, 119.8, 115.4, 114.2, 110.9, 105.0, 94.2, 88.3, 55.2, 21.0; HRMS (EI): calcd for C24H18O2 [M]+ 338.1307, found 338.1307.

2-(2-((4-chlorophenyl)ethynyl)phenyl)benzofuran (17j):

Cl Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 17j (21 mg, 45% yield) as a light yellow solid. Rf=0.7 (10% 1 ethyl acetate in hexanes); H NMR (600 MHz, CD3CN): δ 8.04 (dd, J= 8.3, 1.4 Hz, 1H), 7.76 (d, J= 0.9 Hz, 1H), 7.71 (dt, J= 7.9, 0.9 Hz, 2H), 7.60 (dd, J= 8.7, 4.6 Hz, 2H), 7.58 (dq, J= 7.5, 1.1 Hz, 1H), 7.54 (td, J= 7.6, 1.5 Hz, 1H), 7.46 (dd, J= 8.7, 4.6 Hz, 2H), 7.42 (td, J= 7.5, 1.2 Hz, 1H), 7.37 13 O (ddd, J= 8.3, 6.0, 1.2 Hz, 1H), 7.29 (td, J= 7.2, 0.9 Hz, 1H) ; C NMR (150 MHz, CD3CN): δ 155.4, 154.8, 135.5, 135.1, 134.0, 132.2, 130.4, 130.1, 129.5, 127.9, 126.2, 124.3, 122.7, 122.6, 120.2, 118.4, 112.0, 106.9, 94.1, 90.0; HRMS (EI): calcd for C22H13ClO [M]+ 328.06550, found 328.06446.

173

6-(thiophen-3-yl)naphtho[1,2-b]benzofuran (18a):

S Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 18a (105 mg, 21%) as a light yellow solid. Rf=0.7 (10% ethyl 1 acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.48 (dd, J= 8.4, 0.8 Hz, 1H), 7.97 (d, J= 8.0 Hz, 1H), 7.73 (t, J= 4.1 Hz, 1H), 7.72 (s, 1H), 7.68 (d, J= O 8.0 Hz, 1H), 7.65 (td, J= 8.2, 1.2 Hz, 1H) 7.59 (m, 2H), 7.55 (dd, J= 4.9, 3.0 Hz, 1H), 7.46 (dd, J= 4.8, 1.2 Hz, 1H), 7.45 (td, J= 7.6, 1.4 Hz, 1H), 7.24 (td, J= 7.8, 1.0 Hz, 1H) 13 ; C NMR (150 MHz, CDCl3): δ 156.1, 152.2, 140.6, 132.8, 130.2, 128.9, 128.2, 126.5, 126.3, 126.1, 125.8, 124.7, 123.4, 123.3, 122.6, 122.1, 121.0, 120.6, 117.9, 111.7; UV/Vis (MeOH): max = 287 nm; HRMS (EI): calcd for C20H12OS [M]+ 300.0609, found 300.0622.

6-phenylnaphtho[1,2-b]benzofuran (18b):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 18b (19 mg, 24% yield) as a yellow oil. Rf=0.6 (10% ethyl 1 acetate in hexanes); H NMR (400 MHz, CDCl3): δ 8.49 (d, J= 8.1 Hz, 1H), 7.99 (d, J= 8.0 Hz, 1H), 7.68 (m, 4H), 7.59 (m, 4H), 7.52 (t, J= 6.0 Hz, O 2H), 7.43 (t, J= 8.3 Hz, 1H), 7.19 (t, J= 7.6 Hz, 1H) ; 13C NMR (100 MHz, CDCl3): δ 156.1, 152.2, 139.9, 135.5, 132.8, 129.1, 128.5, 128.3, 127.9, 126.5, 126.3, 126.0, 124.6, 123.5, 122.5, 122.1, 120.9, 120.5, 117.6, 111.7; UV/Vis (MeOH): max = 282 nm; HRMS (EI): calcd for C22H14O [M]+ 294.1045, found 294.1042.

6-(p-tolyl)naphtho[1,2-b]benzofuran (18c): ......

Chromatographic purification (15% ethyl acetate in hexanes) afforded compound 18c (28 mg, 29% yield) as a light yellow. Rf=0.6 (10% ethyl 1 acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.67 (d, J= 8.3 Hz, 1H), 8.45 (m, 1H), 8.07 (d, J= 7.7 Hz, 1H), 8.01 (s, 1H), 7.90 (dd, J= 8.0, 4.6 Hz, 2H), 7.72 (m, 2H), 7.57 (m, 1H), 7.50 (m, 2H), 7.40 (d, J= 7.9 Hz, 2H), O 13 2.48 (s, 3H) ; C NMR (100 MHz, CDCl3): δ 152.3, 138.0, 133.5, 130.8, 129.4, 129.2, 128.9, 128.3, 127.2, 126. 9, 126.89, 125.9, 125.0, 124.7, 123.3, 123.2, 122.0, 117.9, 112.1, 21.3; UV/Vis (MeOH): max = 288 nm; HRMS (EI): calcd for C23H16O [M]+ 308.12012, found 308.12074.

6-(4-fluorophenyl)naphtho[1,2-b]benzofuran (18d):

174

F Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 18d (15 mg, 18% yield) as a light yellow solid. Rf=0.7 (10% 1 ethyl acetate in hexanes); H NMR (600 MHz, CD3CN): δ 8.46 (dq, J= 8.0, 0.8 Hz, 1H), 8.08 (dd, J= 8.4, 0.8 Hz, 1H), 7.78 (dt, J= 8.3, 0.7 Hz, 1H), 7.75 (bs, 1H), 7.74 (dd, J= 3.4, 1.4 Hz, 2H), 7.72 (m, 1H), 7.66 (td, J= 8.1, O 1.3 Hz, 1H), 7.51 (dd, J= 7.2, 1.2 Hz, 1H), 7.48 (dq, J= 7.3, 0.9 Hz, 1H), 13 7.35 (tt, J= 8.9, 2.3 Hz, 2H), 7.25 (td, J= 8.0, 0.7 Hz, 1H) ; C NMR (150 MHz, CD3CN): δ 164.2 (J= 244.5 Hz), , 157.5, 153.4, 137.4 (J= 3.4 Hz), 135.8, 134.3, 132.5, 132.4, 129.8, 128.4, 128.3, 127.9, 125.7, 125.1, 124.4, 123.3, 121.9, 121.7, 116.8 (J= 22.1 Hz), 113.2; UV/Vis (MeOH): max = 287 nm; HRMS (EI): calcd for C22H13OF [M]+ 312.09505, found 312.09368.

6-(4-methoxyphenyl)naphtho[1,2-b]benzofuran (18e):

O Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 18e (38 mg, 32% yield) as a white crystalline solid. Rf=0.6 (10% 1 ethyl acetate in hexanes); H NMR (400 MHz, CDCl3): δ 8.48 (dt, J= 6.8, 0.7 Hz, 1H), 7.98 (d, J= 8.1 Hz, 1H), 7.72 (dt, J= 8.2, 0.8 Hz, 1H), 7.63 (m, 4H), 7.58 (m, 2H), 7.43 (ddd, J= 8.4, 6.0, 1.3 Hz, 1H), 7.20 (ddd, J= 7.6, 2.7, 1.0 O Hz, 1H), 7.10 (dd, J= 8.8, 4.5 Hz, 2H), 3.95 (s, 3H) ; 13C NMR (100 MHz, CDCl3): δ 159.4, 156.1, 152.3, 135.3, 132.9, 132.4, 130.3, 128.2, 126.5, 126.1, 126.0, 124.8, 123.3, 122.5, 122.2, 120.9, 120.3, 117.8, 113.9, 111.7, 55.4; UV/Vis (MeOH): max = 286 nm; HRMS (EI): calcd for C23H16O2 [M]+ 324.11503, found 324.11452.

4-(naphtho[1,2-b]benzofuran-6-yl)benzonitrile (18f):

NC Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 18f (53 mg, 27% yield) as a light red solid. Rf=0.7 (10% ethyl 1 acetate in hexanes); H NMR (400 MHz, CDCl3): δ 8.48 (d, J= 8.1 Hz, 1H), 7.99 (d, J= 8.0 Hz, 1H), 7.83 (q, J= 8.3 Hz, 4H), 7.73 (d, J= 8.2 Hz, 1H), 7.70 O (d, J= 8.1 Hz, 1H), 7.67 (d, J= 8.0 Hz, 1H), 7.64 (s, 1H), 7.46 (d, 8.1 Hz, 1H), 13 7.41 (d, J= 7.9 Hz, 1H), 7.21 (t, J= 7.5 Hz, 1H) ; C NMR (100 MHz, CDCl3): δ 156.1, 152.4, 144.7, 132.3, 132.27, 132.2, 129.9, 129.1, 129.0, 128.4, 127.0, 126.9, 126.4, 124.6, 123.8, 122.8, 121.6, 121.0, 120.9, 116.8, 112.0; UV/Vis (MeOH): max = 281 nm; HRMS (EI): calcd for C23H13ON [M]+ 319.09972, found 319.09982.

6-butylnaphtho[1,2-b]benzofuran (18h):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 18h (124 mg, 23% yield) as a white solid. Rf=0.8 (10% ethyl 1 acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.44 (d, J= 8.0 Hz, O 1H), 8.04 (d, J= 7.7 Hz, 1H), 7.92 (d, J= 7.9 Hz, 1H), 7.75 (d, J= 8.1 Hz, 175

1H), 7.59 (t, J= 7.1 Hz, 1H), 7.56 (d, J= 7.9 Hz, 1H), 7.50 (m, 2H), 7.43 (t, J= 7.6 Hz, 1H), 3.23 (t, J= 7.8 Hz, 2H), 1.89 (quin, J= 7.7 Hz, 2H), 1.58 (sex, J= 7.5 Hz, 2H), 1.06 (t, J= 7.4 Hz, 3H) ; 13 C NMR (150 MHz, CDCl3): δ 155.8, 152.0, 132.0, 131.9, 128.4, 128.36, 127.6, 126.0, 125.6, 125.4, 122.8, 121.8, 121.6, 120.7, 118.3, 111.7, 33.8, 31.8, 22.6, 14.0; UV/Vis (MeOH): max = 285 nm; HRMS (EI): calcd for C20H18O [M]+ 274.1358, found 274.1372.

6-(4-methoxyphenyl)-3-methylnaphtho[1,2-b]benzofuran (18i):

O Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 18i (163 mg, 21% yield) as a light yellow solid. Rf=0.7 (10% 1 ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.37 (d, J= 8.3 Hz, 1H), 7.75 (bs, 1H), 7.69 (dd, J= 8.3, 0.8 Hz, 1H), 7.63 (dd, J= 8.6, 4.4 Hz, 2H), 7.55 (s, 1H), 7.54 (m, 1H), 7.47 (dd, J= 8.5, 1.5 Hz, 1H), 7.41 O (m, 1H), 7.18 (td, J= 7.9, 1.0 Hz, 1H), 7.10 (dd, J= 8.6, 4.1 Hz, 2H), 3.94 13 (s, 3H), 2.58 (s, 3H) ; C NMR (150 MHz, CDCl3): δ 159.4, 156.1, 152.5, 133.3, 132.6, 130.5, 130.3, 128.3, 127.3, 125.7, 124.9, 124.8, 122.8, 122.4, 122.1, 120.8, 118.5, 117.1, 113.9, 111.6, 55.4, 21.9; UV/Vis (MeOH): max = 281 nm; HRMS (EI): calcd for C24H18O2 [M]+ 338.13068, found 338.13043.

6-(4-chlorophenyl)naphtho[1,2-b]benzofuran (18j):

Cl Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 18j (12 mg, 24% yield) as a light yellow solid. Rf=0.8 (10% 1 ethyl acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.49 (d, J= 8.2 Hz, 1H), 7.99 (d, J= 8.1 Hz, 1H), 7.73 (d, J= 8.2 Hz, 1H), 7.67 (td, J= 7.4, 1.0 Hz, 1H), 7.65 (dd, J= 8.1, 4.8 Hz, 3H), 7.60 (td, J= 8.1, 1.2 Hz, 1H), O 7.55 (dd, J= 8.3, 4.5 Hz, 2H), 7.50 (d, J= 7.9 Hz, 1H), 7.45 (td, J= 8.4, 1.3 13 Hz, 1H), 7.21 (t, J= 7.2 Hz, 1H) ; C NMR (150 MHz, CDCl3): δ 156.2, 152.4, 138.5, 134.2, 134.0, 132.8, 130.5, 128.8, 128.3, 126.7, 126.6, 126.2, 124.5, 123.5, 122.7, 122.0, 121.0, 120.6, 117.4, 111.8; UV/Vis (MeOH): max = 288 nm; HRMS (EI): calcd for C22H13OCl [M]+ 328.06550, found 328.06403.

1-ethynyl-2-((2-(p-tolylethynyl)phenyl)ethynyl)benzene (19):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 19 (49 mg, 96% yield) as a light yellow oil. Rf=0.6 (10% ethyl 1 acetate in hexanes); H NMR (400 MHz, CDCl3): δ 7.64 (m, 2H), 7.58 (m, 1H), 7.53 (d, J= 7.9 Hz, 2H), 7.49 (d, J= 7.9 Hz, 1H), 7.34 (m, 3H), 7.18 (d, J= 7.8 Hz, 2H), 7.13 (d, J= 7.8 Hz, 1H), 3.27 (s, 1H), 2.39 (s, 3H) ; 13C NMR (150 MHz, CDCl3): δ 138.5, 132.6, 132.3, 132.1, 131.9, 131.7, 129.0, 128.4, 128.2, 128.0, 127.7, 126.4, 125.9, 125.5, 124.5, 120.2, 93.8, 92.3, 91.7, 87.6, 82.0, 81.5, 21.5; HRMS (EI): calcd for C25H16 [M]+ 316.12520, found 316.12419.

176

2-(2-((2-(p-tolylethynyl)phenyl)ethynyl)phenyl)benzofuran (20):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 20 (65 mg, 44% yield) as a light yellow oil. Rf=0.6 (10% ethyl 1 O acetate in hexanes); H NMR (600 MHz, CDCl3): δ 8.09 (dd, J= 8.1, 1.1 Hz, 1H), 8.01 (d, J= 1.0 Hz, 1H), 7.73 (dd, J= 7.7, 1.2 Hz, 1H), 7.61 (m, 2H), 7.49 (dd, J= 8.3, 0.7 Hz, 1H), 7.47 (td, J= 7.9, 1.3 Hz, 1H), 7.42 (dt, J= 7.3, 0.7 Hz, 1H), 7.36 (m, 2H), 7.32 (d, J= 7.9 Hz, 3H), 7.26 (td, J= 7.1, 1.1 Hz, 1H), 7.12 (dt, J= 7.5, 0.9 Hz, 1H), 7.01 13 (d, J= 8.0 Hz, 2H), 2.30 (s, 3H) ; C NMR (150 MHz, CDCl3): δ 154.2, 153.6, 138.5, 134.3, 132.1, 132.0, 131.5, 131.3, 129.2, 129.0, 128.8, 128.3, 127.9, 127.7, 126.6, 126.0, 125.5, 124.5, 122.7, 121.5, 119.9, 119.6, 110.8, 106.3, 94.0, 93.6, 93.1, 87.6, 21.5; HRMS (EI): calcd for C31H20O [M]+ 408.15142, found 408.15016.

6-(p-tolyl)chryseno[6,5-b]benzofuran (21):

Chromatographic purification (20% ethyl acetate in hexanes) afforded compound 21 (50 mg, 80% yield) as a yellow solid. Rf=0.7 (10% ethyl 1 acetate in hexanes); H NMR (600 MHz, CD3CN): δ 9.03 (dd, J= 7.7, O 2.0 Hz, 1H), 8.54 (dd, J= 7.5, 1.4 Hz, 1H), 8.48 (d, J= 7.9 Hz, 1H), 8.10 (m, 1H), 7.89 (s, 1H), 7.88 (d, J= 8.2 Hz, 1H), 7.84 (d, J= 8.6 Hz, 1H), 7.74 (m, 2H), 7.62 (td, J= 7.3, 1.0 Hz, 1H), 7.59 (td, J= 7.7, 1.1 Hz, 1H), 7.47 (td, J= 7.7, 1.1 Hz, 1H), 7.36 (d, J= 7.9 Hz, 2H), 7.29 (d, J= 7.7 Hz, 2H), 7.19 (td, J= 7.9, 1.4 Hz, 1H), 2.44 (s, 3H) ; 13C NMR (150 MHz, CD3CN): δ 156.2, 152.4, 142.3, 138.7, 136.8, 131.8, 131.3, 130.7, 129.6, 129.35, 129.3, 128.9, 128.5, 128.4, 127.6, 127.5, 127.1, 126.2, 125.9, 125.8, 125.2, 124.8, 123.5, 122.5, 122.2, 121.3, 114.8, 112.0, 21.3; UV/Vis (MeOH): max = 304 nm; HRMS (EI): calcd for C31H20O [M]+ 408.15142, found 408.15049.

177

APPENDIX E

NMR SPECTRA OF STARTING MATERIALS AND CASCADE PRODUCTS (CH. 4)

Unless otherwise noted, all 1H NMRs were run on 400 MHz and 600 MHz spectrometer in 13 CDCl3 and CD3CN and all C NMR were run on 100 MHz and 150 MHz spectrometer in CDCl3 and CD3CN. Proton chemical shifts are given relative to the residual proton signal of the deuterated solvent CDCl3 (7.26 ppm) or CD3CN (1.94 ppm). Carbon chemical shifts were internally referenced to the deuterated solvent signals in CDCl3 (77.00 ppm) or CD3CN (1.4, 118.7). All J-coupling values are reported in Hertz (Hz). UV/Vis data was collected on a Perkin Elmer Lambda 950. All high resolution mass spectrometer data were collected on a JEOL JMS 600 double focusing spectrometer.

16a

Figure 133. 1H NMR spectra of 16a.

178

16a

Figure 134. 13C NMR spectra of 16a.

16b

Figure 135. 1H NMR spectra of 16b.

179

16b

Figure 136. 13C NMR spectra of 16b.

Figure 137. 1H NMR spectra of 16c.

180

16c

Figure 138. 13C NMR spectra of 16c.

Figure 139. 1H NMR spectra of 16d. 181

Figure 140. 13C NMR spectra of 16d.

Figure 141. 1H NMR spectra of 16e. 182

Figure 142. 13C NMR spectra of 16e.

Figure 143. 1H NMR spectra of 16f.

183

16f

Figure 144. 13C NMR spectra of 16f.

16g

Figure 145. 1H NMR spectra of 16g.

184

16g

Figure 146. 13C NMR spectra of 16g.

16h

1 Figure 147. H NMR spectra of 16h.

185

16h

Figure 148. 13C NMR spectra of 16h.

16i

Figure 149. 1H NMR spectra of 16i.

186

Figure 150. 13C NMR spectra of 16i.

16j

Figure 151. 1H NMR spectra of 16j.

187

16j

Figure 152. 13C NMR spectra of 16j.

17a

Figure 153. 1H NMR spectra of 17a.

188

17a

Figure 154. 13C NMR spectra of 17a.

17b

Figure 155. 1H NMR spectra of 17b.

189

Figure 156. 13C NMR spectra of 17b.

17c

Figure 157. 1H NMR spectra of 17c.

190

17c

Figure 158. 13C NMR spectra of 17c.

17d

Figure 159. 1H NMR spectra of 17d.

191

Figure 160. 13C NMR spectra of 17d.

Figure 161. 1H NMR spectra of 17e.

192

17e

Figure 162. 13C NMR spectra of 17e.

17f

Figure 163. 1H NMR spectra of 17f.

193

Figure 164. 13C NMR spectra of 17f.

Figure 165. 1H NMR spectra of 17g.

194

Figure 166. 13C NMR spectra of 17g.

17h

Figure 167. 1H NMR spectra of 17h.

195

17h

Figure 168. 13C NMR spectra of 17h.

Figure 169. 1H NMR spectra of 17i.

196

17i

Figure 170. 13C NMR spectra of 17i.

17j

Figure 171. 1H NMR spectra of 17j.

197

17j

Figure 172. 13C NMR spectra of 17j.

S 18a

Figure 173. 1H NMR spectra of 18a. 198

S 18a

Figure 174. 13C NMR spectra of 18a.

18b

Figure 175. 1H NMR spectra of 18b.

199

18b

Figure 176. 13C NMR spectra of 18b.

18c

Figure 177. 1H NMR spectra of 18c.

200

Figure 178. 13C NMR spectra of 18c.

Figure 179. 1H NMR spectra of 18d.

201

18d

Figure 180. 13C NMR spectra of 18d.

Figure 181. 1H NMR spectra of 18e. 202

18e

Figure 182. 13C NMR spectra of 18e.

18f

Figure 183. 1H NMR spectra of 18f.

203

18f

Figure 184. 13C NMR spectra of 18f.

Figure 185. 1H NMR spectra of 18h.

204

Figure 186. 13C NMR spectra of 18h.

18i

Figure 187. 1H NMR spectra of 18i.

205

18i

Figure 188. 13C NMR spectra of 18i.

18j

Figure 189. 1H NMR spectra of 18j.

206

Figure 190. 13C NMR spectra of 18j.

Figure 191. 1H NMR spectra of 19. 207

Figure 192. 13C NMR spectra of 19.

Figure 193. 1H NMR spectra of 20. 208

Figure 194. 13C NMR spectra of 20.

Figure 195. 1H NMR spectra of 21. 209

Figure 196. 13C NMR spectra of 21.

210

1 13 Position H - C HSQC

1 13 H δ C δ (ppm) (ppm) Figure 197. HSQC NMR spectra of 18a.

8.48 120.6 Direct carbon-hydrogen couplings are analyzed with gHSQC to 14 identify each of the C-H moieties present in this compound. Hydrogens at position 13 and 14 display the most deshielded 7.97 128.2 proton signals, as often observed in similar naphthalene 13 products in other related cascades. In particular, the hydrogen at 7.73 111.7 position 13 has a chemical shift of 7.97 ppm and is coupled to 18 the carbon at 128.2 ppm. The hydrogen at position 14 which has a chemical shift of 8.48 ppm is coupled to the carbon at 120.6 7.72 123.3 ppm. A particularly important signal indicated by the dark 7 purple box reveals the presence of the C-H moiety at position 7. 7.59 126.3 The 6-endo closure pathway is further confirmed by correlations 16 between this significant hydrogen at position 7 and carbons two or three bonds away, in the HMBC shown below. 7.56 128.9 10 Distinguishable signals at the phenylene ring are identified in the adjacent table. 7.46 124.7 20

7.24 123.3 19

211

1 1 13 H δ H - C HMBC (ppm) Figure 198. HMBC NMR spectra of 18a.

2 3 bonds gHMBC experiments identified the long range 1H-13C bonds correlations in the structure. The arrows drawn above 15 6 indicate correlations between protons and carbons 8.48 C , C , 14 4 separated by two or three bonds. Correlations between C H7 and two distinct quaternary carbons located three bonds away, C3 and C9 aid in confirming the formation 7 16 7.97 C , C of the naphthalene ring. 13 H14 couples with two different quaternary carbons, C4 3 7 9 as well as C6, located three bonds away as depicted by 7.72 C ,C ,C 7 the red arrows. H13 couples with C16 and C7 located

1 three bonds away. This signal can be further affirmed 7.73 C by the presence of a correlation signal between H7 and 18 C13, indicated by the purple line. On the thiophene ring, 9 12 10 19 7.56 C C H couples with quaternary C . The singlet proton for 10 H7 also couples C19, located three bonds away. H18 1 1 couples with the adjacent quaternary C , which is the 7.46 C most deshielded carbon of the benzofuran ring. Also 20 coupling with C1 through three bonds is H20. H19 has 18 2 2 7.24 C , C three bond coupling to C as shown by one of the pink 19 boxes/arrows. The absence of sp carbons in the 13C NMR and all of the data given above further confirms the structure of 5a.

212

7.65 7.56 123.4 128.9

7.55 125.8 140.6 7.72 130.2 123.3

7.68 7.97 128.2 120.9 132.7 117.8 7.24 128.9 123.4 7.55 126.1 126.6 152.2 7.46 7.59 124.7 156.1 8.48 126.3 7.73 120.6 111.7

Figure 199. 1H and 13C chemical shifts determined by 2D NMR for compound 18a.

NMR data for compound 21:

213

Figure 200. Full HSQC NMR spectra of 21. 9 10 7 6 11 2 14 3 5 13 16 8 1 4 15

7 8 11 9 10 6 12 5 4 13 3 14 2 O 15 1 16

Figure 201. HSQC NMR spectra of 21 aromatic region.

gHSQC shows clear direct carbon-hydrogen couplings. The methyl group (position 12) is easy to distinguish due to its upfield chemical shift in both the proton and carbon spectra. ( the proton signal at 2.44 ppm coupled to the carbon at 21.3 ppm). Signal 1 has a proton shift at 7.84 ppm which is coupled to the carbon at 112 ppm. The other aromatic C-H correlations are shown in the second spectrum in which the aromatic region is enlarged. Signal 5 correlates the most deshielded proton at 9.03 ppm with the carbon at 127.1 ppm. This proton resonates farthest downfield most likely due to deshielding by the adjacent aromatic ring. Signals 13 (8.54/121.3 ppm) and 16 (8.48/123.5 ppm) originate from the edge of the internal chrysene framework, which experiences some deshielding from the adjacent tolyl ring. In the same position on the other side of the chrysene ribbon, the slightly less deshielded signals 6 (7.74/127.5 ppm), 7 (7.74/125.8 ppm) and 8 (8.10/127.6) correspond to the edge of the molecule. Signal 9 (7.89, 128.5 ppm) is a doublet in proton NMR due to a weak coupling with an adjacent proton. The last signals highlighted in this HSQC are signals 10 (7.36/129.3 ppm) and 11 (7.29/129.35) which are the doublet of doublets from the para-substituted tolyl ring. These are easily identified due to their doubled intensity relative to that of the other signals. All other direct proton-carbon coupling shifts can be seen on the figure below.

214

Figure 202. Full HMBC NMR spectra of 21.

Figure 203. HMBC NMR spectra of 21 aromatic region.

215

gHMBC experiments elucidated long range 1H-13C connectivities, with important couplings highlighted on the two HMBC spectra above. The full HMBC spectrum of 21 immediately reveals the separate correlations that exist between H12 and C11 as well as C24 , both located on the para substituted toluene ring and depicted by the black and red boxes, respectively. All other H-C couplings are observed on the expanded aromatic HMBC. The most deshielded proton, H5 couples with quaternary C21, located three bonds away on the same. Correlation between H8 and C7 on this same ring of the chrysene structure exists and indicated above H9 has three bond coupling with the quaternary C23 of the para substituted toluene ring. On the toluene ring H11 couples with C23 through three bonds, and H10 of the toluene ring couples with the quaternary C22 of the chrysene unit. Correlations are also observed between H-C of the terminus end of the chrysene substructure where H13 couples to quaternary C26 through two bonds. H16 on this same ring couples with C14 through 3 bonds. On the benzofuran substructure are a number of through- bond couplings as well. H3 has two clear couplings with C1 through three bonds as well as coupling with quaternary C17 through three bonds. Considering the absence of any sp carbons in the 13C NMR, which indicates total conversion of the alkynes into sp2-hybridized carbons, as well as the data given above, the structure of 21 was determined.

Figure 204. 1H and 13C chemical shifts determined by 2D NMR for compound 21.

216

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95 Catellani, M. Synlett 2003, 298.

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97 (a) Shibata, T.; Fujiwara, R.; Takano, D. Synlett 2005, 13, 2062. (b) Odedra, A.; Wu, C. –J.; Pratap, T. B.; Huang, C. –W.; Ran, Y. –F.; Liu, R. –S. J. Am. Chem. Soc. 2005, 127, 3406. (c) Oh, C. H.; Kim, A.; Park, W.; Park, D. L.; Kim, N. Synlett 2006, 17, 2781.

98 Hashmi, A. S. K.; Braun, I.; Rudolph, M.; Rominger, F. Organometallics 2012, 31, 644.

99 Examples of such [1,2] shifts; see: (a) Cabello, N.; Jiménez-Núñez, E.; Buñuel, E.; Cárdenas, D. J.; Echavarren, A. M. Eur. J. Org. Chem. 2007, 25, 4217. (b) Nieto-Oberhuber, C.; Pérez- Galán, P.; Herrero-Gómez, E.; Lauterbach, T.; Rodríguez, C.; López, S.; Bour, C.; Rosellón, A.; Cárdenas, D. J.; Echavarren, A. M. J. Am. Chem. Soc. 2008, 130, 269. (c) Dudnok, A. S.; Xia, Y.; Li, Y.; Gevorgyan, V. J. Am. Chem. Soc. 2010, 132, 7645.

100 Hashmi, A. S. K.; Ramamurthi, T. D.; Rominger, F. Adv. Synth. Catal. 2010, 352, 971.

101 Naoe, S.; Suzuki, Y.; Hirano, K.; Inaba, Y.; Oishi, S.; Fujii, N.; Ohno, H. J. Org. Chem. 2012, 77, 4907.

102 Odedra, A.; Wu, C. –J.; Pratap, T. B.; Huang, C. –W.; Ran, Y. –F.; Liu, R. –S. J. Am. Chem. Soc. 2005, 127, 3406.

103 Examples of gold-catalyzed reactions involving hydroamination of hydroarylation; see: (a) Liu, X. Y.; Ding, P.; Huang, J. S.; Che, C. M. Org. Lett. 2007, 9, 2645. (b) Hashmi, A. S. K.; Blanco, M. C.; Kurpejović, E.; Frey, W.; Bats, J. W. Adv. Synth. Catal. 2006, 348, 709. (c) 223

Hashmi, A. S. K.; Blanco, M. C. Eur. J. Org. Chem. 2006, 4340. (d) Hashmi, A. S. K.; Haufe, P.; Schmid, C.; Nass, A. R.; Frey, W. Chem. –Eur. J. 2006, 12, 5376. (e) Gorin, D. J.; Dubé, P.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 14480.

104 (a) Gorin, D. J.; Toste, F. D. Nature, 2007, 446, 395. (b) Patil, N. T.; Yamamoto, Y. Chem. Rev. 2008, 108, 3395. (c) Fürstner, A. Chem. Soc. Rev. 2009, 38, 3208.

105 For alkyne hydroamination to give indoles; see: (a) Acadi, A.; Bianchi, G.; Marinelli, F. Synthesis 2004, 610. (b) Alfonsi, M.; Arcadi, A.; Aschi, M.; Bianchi, G.; Marinelli, F. J. Org. Chem. 2005, 70, 2265. (c) Miyazaki, Y.; Kobayashi, S. J. Comb. Chem. 2008, 10, 355. (d) Praveen, C.; Sagayaraj, Y. W.; Perumal, P. T. Tetrahedron Lett. 2009, 50, 644.

106 For gold-catalyzed electrophilic activation of alkynes toward intramolecular nucleophilic attack at the C-3 position of indoles; see: (a) Ferrer, C.; Echavarren, A. M. Angew, Chem., Int. Ed. 2006, 45, 1105. (b) Ferrer, C.; Amijs, C. H. M.; Echavarren, A. M. Chem. –Eur. J. 2007, 13, 1358. (c) Sanz, R.; Miguel, D.; Rodríguez, F. Angew. Chem., Int. Ed. 2008, 47, 7354. (d) England, D. B.; Padwa, A. Org. Lett. 2008, 10, 3631. (e) Lu, Y.; Du, X.; Jia, X.; Liu, Y. Adv. Synth. Catal. 2009, 351, 1517.

107 Hirano, K.; Inaba, Y.; Takahashi, N.; Shimano, M.; Oishi, S.; Fujii, N.; Ohno, H. J. Org. Chem. 2011, 76, 1212.

108 Hirano, K.; Inaba, Y.; Takasu, K.; Oishi, S.; Takemoto, Y.; Fujii, N.; Ohno, H. J. Org. Chem. 2011, 76, 9068.

109 (a) Neenan, T. X.; Whitesides, G. M. J. Org. Chem. 1988, 53, 2489. (b) Haley, M. M.; Tykwinski, R. R.; Eds. Carbon-Rich Compounds: From Molecules to Materials; Wiley-VCH: New York, 2006. (c) Diederich, F.; Stang, P. J.; Tykwinski, R. R., Eds. Acetylene Chemistry: Chemistry, Biology and Material Science; Wiley-VCH: Weinheim, 2005. (d) Bunz, U. H. F. Angew. Chem. Int. Ed. Engl. 1994, 33, 1073. (e) Tour, J. M. Chem. Rev. 1996, 96, 537. (f) Gholami, M.; Tykwinski, R. R. Chem. Rev. 2006, 106, 4997. (g) Shin, Y.; Fryxell, G. E.; Johnson, C. A., II; Haley, M. M. Chem. Mater. 2008, 20, 981.

110 (a) Curran, D. P. Synthesis 1988, 417, 489. (b) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91, 1237. (c) Wang, K. K. Chem. Rev. 1996, 96, 207. (d) Gansauer, A.; Bluhm, H. Chem. Rev. 2000, 100, 2771. (e) Renaud, P.; Sibi, M. P. Eds. Radicals in Organic Synthesis; Wiley-VCH: Weinheim, Germany, 2001. (f) Sibi, M. P.; Manyem, S.; Zimmerman, J. Chem. Rev. 2003, 103, 3263.

111 (a) Anthony, J. E. Chem. Mater. 2011, 23, 583. (b) Scharber, M. C.; Mühlbacher, D.; Koppe, M.; Denk, P.; Waldauf, C.; Heeger, A. J.; Brabec, C. J. Adv. Mater. 2006, 18, 789.

112 Selected examples from special issue on organic electronics: (a) Wakim, S.; Bouchard, J.; Simard, M.; Drolet, N.; Tao, Y.; Leclerc, M. Chem. Mater. 2004, 16, 4386. (b) Chen, C.-T. Chem. Mater. 2004, 16, 4389. (c) Veres, J.; Ogier, S.; Lloyd, G.; Leeuw, D. Chem. Mater. 2004, 16, 4543. 224

113 Collier, C. P.; Mattersteig, G.; Wong, E. W.; Luo, Y.; Beverly, K.; Sampaio, J.; Raymo, F. M.; Stoddart, J. F.; Heath, J. R. Science 2000, 289, 1172.

114 Selected recent examples: (a) Alabugin, I. V.; Gilmore, K.; Patil, S.; Manoharan, M.; Kovalenko, S. V.; Clark, R. J.; Ghiviriga, I. J. Am. Chem. Soc. 2008, 130, 11535. (b) Vasilevsky, S. F.; Baranov, D. S.; Mamatyuk, V. I.; Gatilov, Y. V.; Alabugin, I. V. J. Org. Chem. 2009, 74, 6143. (c) Baranov, D. S.; Vasilevsky, S. F.; Gold, B.; Alabugin, I. V. RSC Adv. 2011, 1, 1745. (d) Gilmore, K.; Manoharan, M.; Wu, J.; Schleyer, P.v.R.; Alabugin, I. V. J. Am. Chem. Soc. 2012, 134, 10584.

115 Alabugin, I. V.; Gilmore, K.; Patil, S.; Manoharan, M.; Kovalenko, S. V.; Clark, R. J.; Ghiviriga, I. J. Am. Chem. Soc. 2008, 130, 11535. Intramolecular initiation via the “weak link” design: Byers, P. M.; Alabugin, I. V. J. Am. Chem. Soc. 2012, 134, 9609.

116 (a) Nevado, C.; Echavarren, A. M. Chem. Eur. J. 2005, 11, 3155. (b) Gilmore, K.; Alabugin, I. V. Chem. Rev. 2011, 111, 6513. (c) Alabugin, I. V.; Gilmore, K.; Manoharan, M. J. Am. Chem. Soc. 2011, 133, 12608.

117 Baldwin, J. E. J. Chem. Soc. Chem. Commun. 1976, 734.

118 Bürgi, H. B.; Dunitz, J. D.; Lehn, J. M.; Wipff, G. Tetrahedron 1974, 30, 1563.

119 (a) Zhou, Y.; Ji, X.; Liu, G.; Zhang, D.; Zhao, L.; Jiang, H.; Liu, H. Adv. Synth. Catal. 2010, 352, 1711. (b) Song, X. -R.; Xia, X. –F.; Song, Q. –B.; Yang, F.; Li, Y. –X.; Liu, X. –Y.; Liang, Y. –M. Org. Lett. 2012, 14, 3344. (c) For a recent review of metal assisted alkyne cyclizations, see Godoi, B.; Schumacher, R. F.; Zeni, G. Chem. Rev. 2011, 111, 2937.

120 See for example: (a) Ohtaka, A.; Teratani, T.; Fujii, R.; Ikeshita, K.; Kawashima, T.; Tatsumi, K.; Shimomura, O.; Nomura, R. J. Org. Chem. 2011, 76, 4052. (b) Wang, R.; Mo, S.; Lu, Y.; Shen, Z. Adv. Synth. Catal. 2011, 353, 713. (c) Vasilevsky S. F.; Gornostaev L. M.; Stepanov, A. A.; Arnold, E. V.; Alabugin I. V. Tetrahedron Lett. 2007, 48, 1867.

121 (a) Hirano, K.; Inaba, Y.; Takahashi, N.; Shimano, M.; Oishi, S.; Fujii, N.; Ohno, H. J. Org. Chem. 2011, 76, 1212. (b) Hirano, K.; Inaba, Y.; Takasu, K.; Oishi, S.; Takemoto, Y.; Fujii, N.; Ohno, H. J. Org. Chem. 2011, 76, 9068. For the subsequent expansion to substituted naphthalenes, see: Naoe, S.; Suzuki, Y.; Hirano, K.; Inaba, Y.; Oishi, S.; Fujii, N.; Ohno, H. J. Org. Chem. 2012, 77, 4907.

122 Chen, C. -C.; Yang, S. -C.; Wu, M. -J. J. Org. Chem. 2011, 76, 10269.

123 Hashmi, A. S. K.; Braun, I.; Rudolph, M.; Rominger, F. Organometallics 2012, 31, 644.

124 (a) Hundertmark, T.; Littke, A. F.; Buchwald, S. L.; Fu, G. C. Org. Lett. 2000, 2, 1729. (b) Soheili, A.; Albaneze-Walker, J.; Murry, J. A.; Dormer, P. G.; Hughes, D. L. Org. Lett. 2003, 5, 4191. 225

125 The “Pd-free Sonogashira reactions” are likely due to Pd impurities in the ClAuPPh3 catalyst. It has been estimated that as little as 50 ppb Pd impurity can be catalytically active. Livendahl, M.; Espinet, P.; Echavarren, A. M. Platinum Metals Rev. 2011, 55, 212.

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BIOGRAPHICAL SKETCH

Curriculum Vitae

226

Philip M. Byers

Professional Preparation:

2008-2013 Ph. D. The Florida State University, FL, USA. Major: Organic Chemistry. Dissertation: Cascade Reactions for the Synthesis of Polycyclic Aromatic Hydrocarbons and Carbon Nanoribbons. Committee members: I. V. Alabugin, R. Alamo, G. F. Strouse, S. Saha.

2004-2008 B. S. Chemistry, Ithaca College, Ithaca, NY, USA. Major: Chemistry.

2000-2004 Regents Diploma, Gates-Chili High School, Rochester, NY, USA.

Professional Experience:

2007-2008 Novomer INC Research and Development Lab South Hill Business Campus 950 Danby Rd. Suite 198 Ithaca, NY 14850  Lab manager involved with ordering and supplies and keeping lab in working order.  Engineered scale-up process for the synthesis of a novel biodegradable polymer/ plastic.  Worked directly with Ph. D. chemists in a laboratory setting.

Summer 2005 Eastman Kodak Company Building 17 1669 Lake Ave. Rochester, NY 14615  Shipped film worldwide from the initial chemical process of picture/ movie film production.

Membership in Professional Organizations:

227

The American Association for the Advancement of Science.

Teaching Experience as a Teaching Assistant:

E2 Organic Lab IC Undergraduate Fall 2007 CHM2211L Organic Lab FSU Undergraduate Fall 2008 CHM2211L Organic Lab FSU Undergraduate Spring 2009 CHM2211L Organic Lab FSU Undergraduate Summer 2009 CHM2210 Organic Chem. I FSU Undergraduate Fall 2009 CHM2211L Organic Lab FSU Undergraduate Spring 2010 CHM2211 Organic Chem II FSU Undergraduate Summer 2010 CHM2211 Organic Chem II FSU Undergraduate Fall 2010 CHM2211 Organic Chem II FSU Undergraduate Spring 2011 CHM2210 Organic Chem I FSU Undergraduate Fall 2011 CHM2210 Organic Chem I FSU Undergraduate Spring 2012 CHM2211 Organic Chem II FSU Undergraduate Spring 2013

Undergraduate Students Supervised:

1. Vekarious Barnes Chemistry FSU DIS student Summer 2009-Fall 2010 2. Sheeva Yazdani Chemistry FSU DIS student Fall 2009- Spring 2011 3. Artem Bobylev Chemistry FSU DIS student Spring 2011-Summer 2011 4. Brian Lynch Chemistry FSU DIS student Fall 2011 5. Audrey Smith Chemistry FSU DIS student Fall 2011-Summer 2012 6. Julian Rashid Chemistry FSU DIS student Fall 2011-present 7. Ilya Pushkin Chemistry FSU UROP student Fall 2012-present

Refereed Journal and Book Articles:

1. Byers, P. M.; Alabugin, I. V. Radical Reactions. Encyclopedia of Physical Organic Chemistry. Under Review.

2. Byers, P. M.; Rashid, J. I.; Mohamed, R. K.; Alabugin, I. V. Polyaromatic Ribbon/ Benzofuran Fusion via Consecutive Endo Cyclizations of Enediynes. Org. Lett. 2012, 14, 6032-6035. DOI: 10.1021/ol302922t.

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3. Byers, P. M.; Alabugin, I. V. Polyaromatic Ribbons from Oligo-Alkynes via Selective Radical Cascade: Stitching Aromatic Rings with Polyacetylene Bridges. J. Am. Chem. Soc. 2012, 134, 9609-9614. DOI: 10.1021/ja3023626.

4. Shares, J.; Yehl, J.; Kowalsick, A.; Byers, P.; Haaf, M. P. An efficient synthesis of tertiary amines from nitriles in aprotic solvents. Tetrahedron Letters 2012, 53, 4426- 4428. http://dx.doi.org/10.1016/j.tetlet.2012.06.044.

5. Angamuthu, R.; Byers, P.; Lutz, M.; Spek, A. L.; Bouwman, E. Electrocatalytic CO2 conversion to oxalate by a copper complex. Science 2010, 327, 313-315. DOI: 10.1126/science.1177981.

Presentations:

1. Alabugin, I. V.; Gilmore, K.; Gold, B.; Byers, P. Refining Baldwin rules for alkyne cyclizations: From stereoelectronics to cascade reactions. Presentation at 244th ACS National Meeting & Exposition, Philadelphia, PA, United States, August 19-23, 2012 (2012), ORGN-319.

2. Byers, P. Efficient Radical Cascade Reactions for the Synthesis of Graphene and Nanoribbons. Presented at Florida State Organic Seminar (Research Requirement), Tallahassee, FL, United States, November 18, 2010.

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3. Byers, P.; Barnes, V.; Yazdani, S.; Pal, R.; Gold, B.; Alabugin, I. V. Cascade Transformations of Enediynes: Finding the Right Trigger for the Formation of Graphene Sheets. Poster presentation at the Florida Association for Media in Education (FAME), Tampa, FL, United States, May 2010.

4. Byers, P. Concerted Hydroamination Reactions. Presented at Florida State Organic Seminar (Literature Requirement), Tallahassee, FL, United State, December 10, 2009.

5. Shares, J. B.; Byers, P.; Haaf, M. P. An Efficient Synthesis of Tertiary Amines from Nitriles. Presentation at 34th Northeast Regional Meeting of the American Chemical Society, Binghamton, NY, United States, October 5-7 (2006), NRM-342.

Invention:

Published Patent-

Igor V. Alabugin and Philip M. Byers MODULAR SYSTHESIS OF GRAPHENE NANORIBBONS AND GRAPHENE SUBSTRUCTURES FROM OLIGO-ALKYNES. Publication No. US 2013-0109855-A1; FSU 12-027.

Service to University:

Contributed to on campus tutoring (FSU) as well as chemistry outreach program for middle and high school youth.

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