ff.C ErtEOCEEHICJ1L ::tEQUIREHEN'rS .FO'.:i BISHor:; OAR OI<:JI TIC ITY STEREOCEE:tv'dCJ.iL REQUIREMENTS FOR BISHOJ:v10.AROMATICI1J.'Y by BANS JI. COBVER, l\SSOC. IN PURE CHEIVT. i\ Thesis submitted to the School of Graduate studies in ~artial Fulfilment of the Requirements for the Degree Doctor of Philosophy McMaster University (November) 1973 DOCTOR OF P5ILOSOPHY (1973) Mc~AST~R UNIVERSITY (Chemistry) Hamilton, Ontario. Stereochemical Requirements for Bishomoaromaticity l\UTEOR: Eans A. Carver, Assoc. in Pure Chem. (',Jestern l\ustra Lian Institute of Technology) Erofessor 3.F. Childs xiv, 173 11 ABSTRACT OF 1r:F1E DISSERTJITION StereochemicaL Requirements for Bishomoaromaticity To investigate the stereochemical requirements for bishomoaromaticity it was necessary to develop a synthetic scheme that would give suitable precursors in which the stereochemistry could be unambiguously assigned. Arguments are presented in this thesis to suggest that, if bishomo­ aromaticity is to be detected when the two methylene bridges are trans with respect to each other, the l,4-bishomotropyLiu~ systerr.. is more favourably orientated for eye lie delocalization than the 1,J-bishomotropylium system. by reacting benzotropone ethylene ketal with phenyl mercuric trichloromethane, followed by removal of the chLorinec and protecting group, it was possible to synthesize the trans­ 4, 5-benzo-2,J :6,?-bishomotropone. The cis-4,5-benzo-2,3:6,?­ bishomotropone was synthesized by the action of dimethyLoxo­ sulfoniurn methyLide on benzotropone. The stereochemistry in the ciE; and trans isomers was unambiguous Ly established by examining the nmr spectra of the derived alcohols. To determine the effect of the benzene ring in these homoaromatic systems it was necessary to synthesize 4,5-benzo­ 2,3-homotropone. By reacting benzotropone with dimethyLoxo­ iii sulfonium methylide it was possible to obtain a high yield of 4,5-benzo-2,J-homotropone. 'l'he low temperature nmr spectra. of protonated 4,5-benzo-2,3-homotropone and the derived alcohol clearly showed that the benzene ring did not decrease the homoaromatic nature in these systems. The hydroxy substituent, however, had a marlced effect on the homoaromatic nature. The Low temperature nmr spectra of the protonated cis ana trans-4,5-benzo-2,3:6,7-bishomotropones showed that the trans hydroxy cation could be best interpreted as a cyclo­ propylcarbinyL delocalized system and the cis hydroxy cation as a bishomoaromatic species. ·rhP Low temperature nmr spectrum of the trans-L~, 5-benzo­ 2, 3: 6, 7-bishomotropy li um cation also supported the cyclopropyL carbinyL delocalization in this system. In contrast to tl1e hydroxy-substituted system, however, the unsubstituted system was not equilibrating between the two possible equivalent boat conformations. This was attributed to the hydroxy substituent effect on the transition state of the boat-boat equilibrium. In conclusion, arguments are presented that would suggest that the trans-1,J-bishomotropylium cation is not a bishomoaromatic cation as previously reported, but that it can be best represented as a cyclopropyLcarbinyl delocalized system. iv ·ro Val, Richard and Deborah v ACKNOWLEDGEMENTS I wish to express my deep appreciation to Professor Ron Childs for his inspirational guidance and continued encouragement throughout this work. I would like to thank the members of our research group for the many informative discussions and in particular B. Sayer who obtained many of the nmr spectra. Appreciation is also extended to the Ontario Government, National Research Council of Canada and McMaster University for their financial assistance. I am grateful especially to Val, my wife, who typed this manuscript and without whose Love and patience this work could not have been completed. vi T.ABLE: OF CONTENTS Descriptive Note •••••••••••••••••••••••• ii Abstract of the Dissertation•••••••••••• iii ~reface ••••••••••••••••••••••••••••••••• v Acknowledgements •••••••••••••••••••••••• vi Table of Contents ••••••••••••••••••••••• vii List of Tables •••••••••••••••••••••••••• xiii List of Figures ••••••••••••••••••••••••• xiv J\. IK·T~ODUCTION AND GENEHJ\L DISCUSSION" SEC11I ON ONE =·~IS'l'oqrc11L BACKGROUND.......................... 2 1' ~·.. i CI 1 ~l\ 'I' I(; I rry • •••••••••••••••••••••••• • ••••••••• • 3 ·:~OL01'1"9Gr~ATICITY - GENERJ\L CONCEP11 ~'..'JD l...~·0Iv'13NCLJ\'l1 URE. • • • • • • • • • • • • • • • • • • • • • • • • • • • • • 6 hONOHOl~WARO!·'.lATICITY............................ Ll (a) Monohomotropylium Cation•••••••••••••••••• 11 Coupling Constants in the Homo- Tropy 11 um Cation..................... 16 ( b) Substituted Homotropylium Cations ••••••••• 21 l-Methyl-Cationsand ·t-Phenylhomotropylium .............................. 21 L-Hydroxy- and l-Methoxyhomotropylium Cati·ons •.•••••••••. •.• ....•• ~......... 23 vii 2-Hydroxy- and 4-Hydro:xyhomotropy lium Cations.............................. 25 J1pplication and Velidity of the Johnson Bovey Equation............... 27 8-Substituted Homotropylium Cations....... 28 Benzo- and Dibenzohomotropylium Cations.............................. 33 SECTION THREE BISHOMOAROMATICITY............................. 41 (a) L,4-Bishomotropylium Cations.............. 41 Kinetic Evidence.......................... 48 (b) l,J-Eishomotropylium Cation••••••••••••••• 52 (c) Comparative and Theoretical Treatment · of the Tropylium, Homotropylium and Bishomotropylium Cations ••••••••• 55 B. flESUL'rS AND DISCUSSION SECTION ONE STJiT ~r:;ENT OF THE PROBLEM. • • • • • • • • • • • • • • • • • • • • • • 59 GENH:RAL SYNTHETIC CONSIDERATIONS............... 63 (a) Nature of Precursor....................... 63 (b) Potential Methods for the Cyclo­ propanation of Benzotropone.......... 64 i1ddition of Methylene Using Diazo Compounds............................ 66 Simmons-Smith Reagent..................... 67 Dimethyloxos~lfonium Methylide and Dimethylsulfonium JYiethylide as Methylene Transfer Agents............ 68 Generation and Addition of Dihalo­ carbenes to Olefinic Bonds........... 70 viii (I), ) i--re Limina.ry E:xperiments ••••••••••••••••••• ?2 ( 1~•-' 'I Preparation of 4,5-Penzotropone Ethylene Ketal ••••••••••••••••••••••• ?4 (c) DihaLocarbene ~ddition to the Ethylene Ketal of 4,5-Benzotropone ••••••••••••••••••••• 79 (a ) Reaction of Dimethyloxosulfonium Methylide with 4,5-Benzotropone •••••• f O SSCTION I'WO M·'iR SFECTR.A OF' crs- .AND T'R/\1\S-4, 5-BENZ0­ 2, J :6, 7-BISHOM.OTROPOKi!:S. :-:-;:-. • •• • • • • • • • • • • • • • • • 83 STEREOCHEMISTRY·••••••••••••••••••••••••••••••• 87 SECTIOT:~ THREE: GE1':E:Bi1TION MID OBE>EB.V.NrION OF THE hONO- ANTI BISHGrf:OTROPYLIW CATIONS.................. 90 (a) The 4,5-Eenzo-2,J-Homotropylium Cation............................... 90 (b) The l-Hydroxy-4,5-Benzo-2,J-Romo­ tropylium Cation..................... 95 ( c) 220 MHz Nmr Spectrum of the 2-Hydroxy­ homotropy Li um Cation••••••••••••••••• 97 (a) Frotonated Cis and ~-4,5-Benzo- 2,3:6,7-Bishomotropones •••••••••••••• 99 (e) Frotonation of Cis- and Trans- Alcohols 111-0H and 112-0H••••••••••• 104 ( f) Conclusions and General Discussion•••••••• LOS GE.NERJ\ L l'ROCEDURES. • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • L L.4 ~uclear ~agnetic Resonance Spectra (nmr)....... LL4 ~ethylene Chloride........................ L15 Carbon Tetrachloride•••••••••••••••••••••• LL5 ix Infrared Spectra••••••••••••••••••••••••••••••• 116 I/1a.ss Spectre.••••••••••••••••••••••••••••••••••• LL6 !:'~ e l ting 1) o1nt s . • . • . • . • . • • • . LL6 GEFE1.ll'l'ION, OBSERVJ1TION Mm QUEKCEING OF 81\TIOJ>TS •••••••••••••••••••••••••••••••••••••••• LL6 ·r1·otonations ••.••.•.... ; .••......•.•.....•..... 1L7 Method A··•••••••••••••••••••••••••••••••• LL? ~ethod B.................................. 112 Quenching of Cations........................... LL9 2,7-Dicarbomethoxy-4,5-Penzotropone............ L21 2,7-Dicarboethoxy-4,5-Benzotropone............. 121 2,7-Dicarboxylic J\cid-4, 5-Benzotropone......... 122 4,5-Benzotropone (110)......................... L22 Reaction of 4,5-Benzotropone (LlO) with ~iazomethane in Ether..................... L2) r;eaction of 4,5-Eenzotropone (lLO) with fhenyl ~ercuric TrichLoromethane.......... L2J :;e1:1ct ion of L~, 5-Benzotropone ( L LO) with the Simmons-Smith Reagent ••••••••••••••••••••• L24· 7-Hydroxy-J,4-Benzocycloheptatriene•••••••••••• L25 Reac~ion of 7-Hydroxy-J,4-Benzocycloheptatriene with the Simmons-Smith Reagent •••••••••••• 125 _:,_eE1 cti on of 4, 5- r~enzotropone ( LlO) with ~thylene Glycol ••••••••••••••••••••••••••• L26 L-:thoxy-4,5-EenzotropyLium Fluobor~te .S,8.lt (130) •.••••••.••••••••••••••••••••••• I?'/,_ ....... , .,,_, i: , 5-?enzotropone sthy Lene Ke ta L ( L2 5) •••••••••• L;:_ / ~cce.cti on of 4, 5-:Senzotropone Ethy Lene l; etal (125) and Phenyl Mercuric Tribromethane............................. L2~ ~eaction of 4,5-RenzotroDone ittylene r:.etal (125) and Phenyl Y.ercuric Trichloromethane•••••••••••••••••••••••••• L29 x frans-4,5-Benzo-2,J:6,?-Bishomotropone --Ethylene ZetaL (138)...................... LJL ~is-4,5-Benzo-2,3:6,7-Bishomotropone - Ethylene Keta l ( 137)...................... 132 rrans-8,8,9,9-Tetradeutero-4,5-Benzo -- 2, 3: 6, ?-Bishomotropone Ethy Lene Ketal (LJB-D) ••••••••••••••••••••••••••••• 132 ;1s-8,8,9,9-Tetradeutero-4,5-Benzo­ - 2,J:6,?-"Sishomotropone Ethylene ietal (13?-D)............................. LJ2 ~Crans-4,5-Benzo-2,3:6,7-Bishomotropone -- ( LL2)....... •• • • • • • • • • • • • • . • • •• • • • • • • • • • • 1.33 Trans-8,8,9,9-Tetradeutero-4,5-Benzo­ 2,3:6,