Organic Chemistry IV
Organometallic Chemistry for Organic Synthesis
Prof. Paul Knochel LMU 2014
1 OCIV Prüfung: Freitag 11. Juli 2014 9-11 Uhr Baeyer HS
Wiederholungsklausur: Donnerstag 11. September 2014 12-14 Uhr Baeyer HS 2 Recommended Literature
1. F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry, Fifth Edition Part A and Part B, Springer, 2008, ISBN-13: 978-0-387-68346-1 2. R. Brückner, Organic Mechanisms, Springer, 2010, ISBN: 978-3-642- 03650-7 3. L. Kürti, B. Czako, Strategic applications of named reactions in organic synthesis, Elsevier, 2005, ISBN-13: 978-0-12-429785-2 4. N. Krause, Metallorganische Chemie, Spektrum der Wissenschaft, 1996, ISBN: 3-86025-146-5 5. R. H. Crabtree, The organometallic chemistry of transition metals, Wiley- Interscience, 2005, ISBN: 0-471-66256-9 6. M. Schlosser, Organometallics in Synthesis – A manual, 2nd edition, Wiley, 2002, ISBN: 0-471-98416-7 7. K. C. Nicolaou, T. Montagnon, Molecules that changed the world, Wiley- VCH, 2008, ISBN: 978-527-30983-2 8. J. Hartwig, Organotransition Metal Chemistry: From Bonding to Catalysis, Palgrave Macmillan, 2009, ISBN-13: 978-1891389535 9. P. Knochel, Handbook of Functionalized Organometallics, Volume 1 und 2, Wiley-VCH, 2005, ISBN-13: 978-3-527-31131-6
3 Importance of organometallics
4 Industrial production
Industrial annual production of various organometallics
Organometallic production [T / year] Si 700 000 Pb 600 000 Al 50 000 Sn 35 000 Li 900
5 Organometallic reagents and catalysts for the organic synthesis
organometallic reagents:
CO2Me ZnCl CH2 AlMe2 BuLi Cp2Ti HClZrCp2 Cl MgBr O Me Tebbe reagent Schwarz reagent organometallic catalysts:
Mes N N Mes Pd(PPh3)4 CpCo(CO)2 RhCl(CO)2 ClRh(PPh3)3 2 Cl Ru Wilkinson's catalyst Cl Ph PCy3
Grubbs II catalyst
Cp
6 Historic point of view
1757 - Louis Cadet de Gassicourt (parisian apothecary)
E. Frankland (1848), University of Marburg, initial goal: synthesis of an ethyl radical
Universität Marburg (1848)
2/3Tl 2 Na 2/3Et Tl Et2Zn 2Et Na 3 -Zn(0) -Zn(0)
7 Organometallic chemistry of the XIX century
Frankland 1848, 1863 O OH Et O Et O Et Et-I + Zn Et Zn Et + O Et Et O O Beilstein 1862, Saytzeff 1870, Wagner 1875
O OH Et O Et O Et Et-I + Zn + O Et Et O O
Barbier 1899
O OH ++Me-I Mg Me O Et Et
Ph. Barbier Comptes Rendus de l'Académie des Sciences, 1899, 128, 110
8 Organometallic chemistry of the XIX century
H Mg H I I Et H H Mg O H H Et O O Et Et Et Et
Mg Ph-CHO OH Br MgBr ether Ph
reactif de Grignard
V. Grignard
Comptes Rendus de l'Académie des Sciences, 1900, 130,1322
9 Reactivity of the Grignard reagents
10 Historic point of view
Victor Grignard (1900)
Karl Ziegler (1919)
11 Historic point of view first transition metal organometallics:
Hein (1919)
12 Historic point of view 1951 : synthesis of ferrocene
Pauson (Scotland) 7. August 1951 Miller 11. June 1951 H H FeCl + 2 300 °C MgBr (C5H5)2Fe + Fe Smp.: 172 °C G. Wilkinson 1952 structural proposal by Pauson
correct structure by G. Wilkinson and R. B. Woodward
G. Wilkinson, R. B. Woodward J. Am. Chem. Soc. 1952, 74, 2125 Fe R.B. Woodward J. Am. Chem. Soc. 1952, 74, 3458
ferrocene
FeCl3 MgBr+
R. B. Woodward 13
H. Sitzmann J. Am. Chem. Soc. 1993, 115, 12003 radical formation Goal of the lecture main goal of this course: applications of organometallic compounds in modern organic synthesis
Y.-H. Chen, Angew. Chem. Int. Ed. 2008, 47, 7648.
14 General synthetic methods for preparing organometallic reagents
classification according to starting materials
direct synthesis via an oxidative addition and halogen-metal exchange
15 Classification according to starting materials
transmetalation
16 Classification according to starting materials
metalation
17 Classification according to starting materials
carbometalation and hydrometalation
18 Synthesis starting from organic halides
direct synthesis - oxidative addition
driving force of the reaction:
19 Direct Synthesis - Oxidative Addition examples:
O O Mg BuBr BuMgBr Bu2Mg + Br2Mg1 O O ether
H 2CrCl + CrCl Br + 2 Me CrCl2 3
pure E-isomer E/Z-mixture 20 Direct Synthesis - Oxidative Addition
mechanism:
P. Knochel Tetrahedron Lett. 1986, 27, 5091 21 Activation of the metal: the Rieke-approach activation of the metal: R. D. Rieke, Science 1989, 246, 1260
Mg + PhOH PhO Br 20 °C, 5 min PhO MgBr
Mg* CO2 PhO MgBr PhO CO2H -78°C, 1h 70%
Activation of lithium: formation of soluble Li-sources:
22 P.P. Freeman, L.L. Hutchinson J. Org. Chem. 1983, 48, 4705 Mechanism of the metal insertion
Br Li Li Li-DBB (2 equiv.) +
80: 20
loss stereochemical information
H.M. Walborsky: J. Am. Chem. Soc. 1989, 11, 1896
radical mechanism 23 Preparation of functionalized organometallics
O O
Zn, THF 25 °C, 6h
O O I ZnI O O
P. Knochel, J. Org. Chem. 1988, 53, 2390 P. Knochel, Org. React. 2001, 58, 417.
A. Krasovskiy, V. Malakhov, A. Gavryushin, P. Knochel, Angew. Chem. Int. Ed. 2006, 45, 6040. 24 Preparation of functionalized organometallics
Br MgBr SMe
Mg, LiCl MeSO2SMe THF, -10 °C, 20 min
OBoc OBoc OBoc 91% 92%
2 2 2
2
2
F. Piller, P. Knochel Chem. Eur. J. 2009, 15, 7192 25 Preparation of functionalized organometallics
activation of Al using LiCl and TiCl4, BiCl3, PbCl2 or InCl3
T. Blümke, Y.-H. Chen, P. Knochel Nature Chemistry, 2010, 2, 313
A. Metzger, P. Knochel Org. Lett. 2008, 10, 1107 26 Extension to insertion reactions to C-S bonds
S. Rychnosvsky J. Org. Chem. 1989, 54, 4982; J. Org. Chem. 1990, 95, 5550 27 The Halogen-Metal-Exchange
driving force: the most stable carbanion is always formed
R HC C CH3 CH2R HC R CR3
2 Csp C 3 sp Csp
28 The Halogen-Metal-Exchange
1939: the Wittig-Gilman reaction
Br THF Li + BuLi + BuBr -78 °C
tBuLi Bu Bu Br 2equiv. Li + + tBuH
tBuLi Bu + H LiBr Li + Br + H Li
tBuLi MeOH I + 2MeOH Li H 2 equiv. 29 93% The Halogen-Metal-Exchange
mechanism:
R1 I R2 R1 I + R2 Li R1 Li + R2 I Li
H. J. Reich, A. W. Sanders, A. T. Fiedler, M. J. Bevan J. Am. Chem. Soc. 2002, 124, 13386 30 The Halogen-Metal-Exchange : tolerance of functional groups
31 The iodine- magnesium-exchange: compatibility with a nitro group
32 A secondary iodine/lithium exchange on cyclohexyl iodides
33 A secondary iodine/lithium exchange on cyclohexyl iodides
34 A secondary iodine/lithium exchange on cyclohexyl iodides
35 Acyclic systems: stereospecific I/Li exchange reaction Acyclic systems: stereospecific I/Li exchange and reactions with C-electrophiles
O tBuLi OMe ANTI R N 2.2 equiv; 0.2 M Me OTBS OTBS OTBS O (2.5 equiv) I added slowly in 10 min Li R -100 oC, Me Me 74% Me 3:2 hexane/Et2O (dr = 98:2) >dr= 96:4 O OMe tBuLi R N SYN 2.2 equiv; 0.2 M Me OTBS OTBS O OTBS (2.5 equiv) added slowly in 10 min Li I R -100 oC, Me 75% Me >dr=6:94 Me 3:2 hexane/Et2O (dr = 3:97)
OTBS OTBS OTBS OTBS OTBS OTBS
O H O H O Ph O Ph O CF3 O CF3
80 % yield 70 % yield 66 % yield 68 % yield 67 % yield 65 % yield
dr = 92:8 dr =9:91 dr =97:3 dr =6:94 dr =96:4 dr =5:95
G. Dagousset, K. Moriya, R. Mose, G. Berionni, K. Karaghiosoff, P. Knochel in press, 2013 Stereoconvergent synthesis of Li-reagents
1. tBuLi, -50°C, 15 min 1. tBuLi, -50°C, 15 min
hexane / Et2O=4:1 hexane / Et2O=4:1 TBSO I TBSO I 2. Me2S2 TBSO SMe 2. Me2S2
Stereoretention dr =97:3 dr =96:4 Stereoinversion dr =97:3 anti syn 58-60 % 1. tBuLi, -50°C, 15 min TBSO I TBSO E TBSO Li TBSO Li hexane / ether = 4 : 1
dr =50:50 2. E+
SiPh3 O O TBSO O TBSO B SBu TBSO CHO TBSO TBSO CO2Et TBSO
+ + + + + + E = Cl-CO Et E = E = Pin-OMe E =Bu2S2 E =DMF E =DMF 2 SiPh3 60 % 74 % 67 % 67 % 63 % 73 % dr =94:6 dr =92:8 dr =96:4 dr =96:4 dr =99:1 dr =97:3
D. Didier, K. Moriya, 2014 The iodine/zinc-exchange
catalysis of the halogen-metal exchange
F. Kneisel, P. Knochel Angew. Chem. Int. Ed. 2004, 43, 1017 39 The Halogen-Metal-Exchange indole-synthesis NMe2 1) iPrMgBr THF, -20 °C, N 5min EtO2C I I OMe 2) Br N Me H I . CO2Et CuCN 2LiCl 90% -20 °C, 30 min 3) H+ D. M. Lindsay, W. Dohle, A. E. Jensen, F. Kopp, P. Knochel Org. Lett., 2002, 4 , 1819
CN CN iPrMgCl LiCl PhCHO NC
OH -7 °C, 3 h 0°C Br MgCl Ph 81%
Cl Li iPrMgCl LiCl i-Pr Mg Cl
A. Krasovskiy, P. Knochel Angew. Chem. Int. Ed. 2004, 43, 3333 40 Transmetalation
a)
the most stable carbanion is linked to the most electropositive metal
41 Transmetalation
W. C. Still, J. Am. Chem. Soc. 1980, 102, 1201 42 Transmetalation
b)
43 Transmetalation
E. Nakamura, I. Kuwajima J. Am. Chem. Soc. 1984, 106, 3368
44 Transmetalation
T. Imamoto, Y. Sugiyura, N. Takiyama, Tetrahedron Lett. 1984, 25, 4233
OH O HO MgCl MgCl
LaCl3 2LiCl 0°C,0.5h 93%
A. Krasovskiy, F. Kopp, P. Knochel Angew. Chem. Int. Ed. 2006, 45, 497 45 Transmetalation
M. Reetz, D. Seebach Angew. Chem. 1983, 95, 12
A. Maercker, M. Theis, A. Kos, P. Schleyer, Angew. Chem. 1983, 95, 755 46 Transmetalation
boron / zinc-exchange
F. Langer, L. Schwink, P. Knochel J. Org. Chem. 1996, 61, 8229 47 Transmetalation
boron / zinc-exchange Zn 2 Ph
94% ee
BH Ipc 2 BH Ph Ph 1) Et2BH Ph 2) Et Zn (-)-IpcBH2 2 3) CuCN.LiCl Cis: trans > 98:2 99% ee 94% ee Br 4) 94% ee, 44%
L. Micouin, M. Oestreich, P. Knochel Angew. Chem. Int. Ed. 1997, 36, 245
48 Nature of the carbon-zinc bond
49 Metalation (starting from a compound with an acid proton)
kinetic criteria (kinetic acidity)
4 PhCH2Li reacts with benzene 10 times faster than with MeLi
PhCH2Li is a monomer in THF, MeLi a tetramer 50 Directed metalation
51 Metalation
BuLi, THF BuLi O S Li 0°C O S Hexane Li O S thermodynamic control kinetic control
N Li Li OLi (2 equiv.) OH 2 BuLi OLi Li S -78 °C S THF S O THF O -78 °C O thermodynamic control kinetic control
rearrangement
52 Metalation
directed lithiation
DMG DMG DMG Li E R-Li E+
DMG = directing metalating group
V. Snieckus, Chem Rev. 1990, 90, 879
O O NR > 2 O OMe Hal O NR2 > O2S > O N > >
P. Beak, V. Snieckus, Angew. Chem. Int. Ed. 2004, 43, 2206 53 Metalation
54 Metalation
A. Krasovskiy, P. Knochel Angew. Chem. Int. Ed. 2006, 45, 2958 R. E. Mulvey, Angew. Chem. Int. Ed. 2008, 47, 8079
F. M. Piller, P. Knochel Org. Lett. 2009, 11, 445 55 Metalation
O O O O O O TMPMgCl LiCl I EtO OEt EtO OEt 2 EtO OEt THF, -30 °C, 1 h Br Br MgCl Br I 80%
O. Baron, P. Knochel Angew. Chem. Int. Ed. 2006, 45, 2958
Cl FeCl2 LiCl N Mg Li N Fe 2MgCl2 4LiCl 25 °C, 3h 2 Cl
O OEt O OEt CO2Et H Fe TMP Fe I CO2Et 2 2 CO2Et 25 °C, 3 h F F F F (10 mol%) 80% 25 °C, 12 h
S. Wunderlich, P. Knochel Angew. Chem. Int. Ed. 2009, 48, 9717 56 Frustrated Lewis Pairs
D. Stefan, G. Erker Angew. Chem. Int. Ed. 2010, 49, 46
H. C. Brown J. Am. Chem. Soc. 1942, 64, 325
57 Frustrated Lewis Pairs
BF3·OEt2 LiTMP PhCHO Ph N 0°C,0.25hN -78°C,0.25hN Li -78°C,1h N
BF3 BF3 OH 85 % Kessar et al, J. Chem. Soc., Chem Commun. 1991,570
I Ph Ph Ph CO Et 1) BF3·OEt2, 2
N 2) TMPMgCl·LiCl, N MgCl·LiCl ZnCl2; N -40 °C, 20 min Pd(dba)2 (5 mol %), BF3 TFP (10 mol %) CO2Et 84 % Ph
Ph 1) N BF3·OEt2 + "TMPMgCl·LiCl·BF " 3 N I TMPMgCl·LiCl -40 °C, 10 min 76 % stable up to -20 °C 2) I2 T°C > -20 °C
TMPBF2 +MgCl(F)
M. Jaric, B. Haag, A. Unsinn, K. Karaghiosoff, P. Knochel Angew.Chem.Int.Ed.2010, 49,5451 58 Frustrated Lewis Pairs
B3LYP/6-31G**,def2-SVP
BF3·THF THF N TMPMgCl(THF) N F 2 B Mg + TMPMgCl(THF)2 F N -4.8 kcal/mol F Cl -1.30 kcal/mol BF3
‡ ‡ dE0 =12.4kcal/mol dE0 = 1.9 kcal/mol
N N F H H THF F N Cl B N N Mg F B Mg F F F Cl THF -TMPH
F N B F N BF3 N MgCl(THF) Cl -13.5 kcal/mol BF3 Mg F MgCl(THF) THF
M. Jaric, B. Haag, A. Unsinn, K. Karaghiosoff, P. Knochel Angew. Chem. Int. Ed. 2010, 49,5451 59 Frustrated Lewis Pairs
TMP-MgCl BF3
F F N H N B F F TMP F TMP-MgCl ClMg
CO2Et
F 1) TMPMgCl LiCl F -78 °C, 30 min 1) BF3 OEt2, 0°C N 2) ArI, Pd(0) 2) TMP-MgCl F N -78 °C, 30 min CO2Et 3) ArI, Pd(0) 72% N 77%
Jaric, M.; Haag, B. A.; Unsinn, A.; Karaghiosoff, K.; Knochel, P Angew. Chem. Int. Ed. 2010, 49, 5451.
60 Metalation
S. Wunderlich, P. Knochel Angew. Chem. Int. Ed. 2007, 46, 7685
M. Mosrin, P. Knochel Org. Lett. 2008, 10, 2497 M. Mosrin, P. Knochel Chem. Eur. J. 2009, 15, 1468 61 M. Mosrin, P. Knochel Org. Lett. 2009, 11, 1837 Zincations in the presence of ester and nitro groups
>95:5
1) TMPZnCl.LiCl (1.1 equiv), THF, 25 °C, 30 min MeO2C O NO2 2) CuCN.2LiCl MeO2C O NO2 Br 3) 80 %
1) TMPZnCl.LiCl Cl (1.1 equiv), THF, Cl CF 25 °C, 15 min 3 N N N N 2) Pd(dba) (3 mol%), N 2 N N P(o-furyl) (6 mol%) N MOM 3 MOM I 95%
Marc Mosrin, P. Knochel, Org. Lett. 2009, 11, 1837-1840. CF3
NO2 NO2 TMPZnCl·LiCl NO2 (1.1 equiv) CuCN·2LiCl (5 mol%) R R R ZnCl H THF,-50°C.1h allyl bromide (1.2 equiv) -20°C,2h R= Ph, Cy R= Ph: 69% R= Cy: 70%
Tomke Bresser, P. Knochel, Angew. Chem. Int. Ed. 2011,50,1914 62 Trifunctionalization of the purine scaffold using Mg and Zn organometallics
1) TMPZnCl·LiCl,25°C,30min 2) Pd(dba)2,tfp, I OMe Cl 40 °C, 12 h Cl OMe N N N N
TMS N N TMS N N OMe OMe 72%
CO2Et Pd/C, NH4HCO2 MeOH, 40 °C 1) TMPZnCl·MgCl2·LiCl, MW, 90 °C 2) Pd(dba) ,tfp, 2 OMe 25 °C, 12 h OMe I CO2Et N N N N TMS N N TMS N N OMe OMe 64% 90%
I2, CsF, MW CO Et 2 100 °C, 12 h CO2Et 1) iPrMgCl, -78 °C 2) ZnCl2, -78°Cto0°C OMe 3) OMe N CF3CO2 N N N N Me N I N N 2 N N OMe OMe 60-80% 85% 63 S. Zimdars; X. Mollat du Jourdin; F. Crestey; T. Carell; P. Knochel. Org. Lett, 2011, 13, 792–795 Lanthanations and manganation of heterocycles
Br Br Br OH TMP2Mn·2LiCl Mn N N tBuCHO N (0.6 equiv) 2 tBu S S S N THF, 0 °C, 2.5 h N 0°C,3h N Br Br Br 7
S. Wunderlich, M. Kienle, P. Knochel, Angew. Chem. Int. Ed. 2009,48, 7256. O La TMP La·5LiCl O 3 EtO C 3 EtO2C (0.35 equiv) 2 O THF, -20 °C, 45 min Cl N Cl N Cl N 74% La HO NC TMP3La·5LiCl NC 3 O (0.35 equiv) NC Cl N THF, -30 °C, 45 min Cl N 7 Cl N
S. H. Wunderlich,P.Knochel,Chem. Eur. J. 2010, 16, 3304-3307. 64 Asymmetric metalation using (S)-(-)-spartein
Ti(OiPr) Me O N BuLi Me O N 4 Me OCb (-)-spartein Inversion H H O Li O (iPrO)4Ti Cb Li Me H Me H H R Me RCHO Ti(OiPr)4 OH OH R H R O CbO H CbO CbO Li 82-92% ee
D. Hoppe, et al. Pure Appl. Chem. 1994, 66, 1479.
P. Beak J. Org. Chem. 1997, 62, 7679 65 Asymmetric metalation using (S)-(-)-spartein
D. Hoppe Tetrahedron Lett. 1992, 33, 5327
66 Configurational stability
2 2
3 3
R. E. Gawley, J. Am. Chem. Soc. 2005, 127, 449 67 Diastereoselective transmetalation
O OMOM OMOM OMOM BuLi Ph SnBu3 THF, -78 °C Ph Li Ph Me Me Me OH
O OMOM OMOM OMOM BuLi Ph Li Ph Ph SnBu3 THF, -78 °C Me Me Me OH
Me O O
Ph Li Me
W. C. Still J. Am. Chem. Soc. 1980, 102, 1201 68 Diastereoselective transmetalation
P. G. McDougal, Tetrahedron Lett. 1988, 29, 2547 69 Carbometalation
syn-addition R1 Met R H + R1 Met R H
Negishi-reaction: carboalumination
R H R H Me3Al PhCHO R H CHCl2 Me AlMe2 Me Ph Cp2ZrCl2 cat. HO 79% E. Negishi J. Am. Chem. Soc. 1976, 98, 6729
1 CuBr, Me S R2 H R Cu MgBr2 1 2 1 R MgBr R Cu MgBr2 syn-addition R2 H >90% Normant-reaction: carbocupration Review: A. Alexakis, J. F. Normant, Synthesis 1981,841. 70 Carbometalation
H
Cu MgBr2 1) ether, -10 °C + Me3SiO 2) H O OH H 3
81% A. Alexakis, J. F. Normant, J. Organomet. Chem. 1975, 96, 471
Tamoxifen-Synthesis: Carbozincation
T. Stüdemann, P. Knochel Angew. Chem. 1997, 109, 132 71 Carbometalation, hydrometalation
ZnBr ZnBr Hex MgX Hex THF MgX > 90%
P. Knochel, J. F. Normant Tetrahedron Lett. 1986, 27, 1039; 1043; 4427
B(OBu)2 B(OH)2 "2 HgCl +2OH " HgCl B(OBu)2 HBH2 2 Me Me Me in situ BH2 B(OH)2 HgCl
D. Matteson, J. Org. Chem. 1964, 29, 2742
72 Hydrometalation and application of organoboranes in organic chemistry
hydroboration
73 Hydroboration
selective hydroborating reagents
H. C. Brown, E. Negishi J. Am. Chem. Soc. 1975, 97, 2799
74 Hydroboration
catecholborane
O Bu H O Bu BH B O O >90% A. Arase, et al., Synth. Comm. 1995, 25, 1957.
O BH O OH Ph PCy2 O O Ph B 90%; 93% ee PCy2 Ph Rh+ cat., -35 °C
S. Demay, M. Lotz, P. Knochel Tetrahedron: Asymmetry 2001, 12, 909 75 Hydroboration amination
cHex N NN cHex N N 2 Me Me Me Me BCl2 1) HBCl2 BCl2 BCl2 N cHex 2) cHex N N N
H2O
Me NHcHex
90%
H. C. Brown, et al. Tetrahedron 1987, 43, 4079
76 Hydroboration stereoselective synthesis of olefins
Z-olefins
Bu Bu I H I2 cHex2BH + Bu H OH B(cHex) NaOH cHex 2 H B
cHex
I cHex I H I H H B(cHex)(OH)2 OH- B(cHex)(OH) Bu Bu Bu H H H B(cHex)(OH)2 cHex cHex
Bu cHex
G. Zweifel, et al. J. Am. Chem. Soc. 1972, 94, 6560. 77 Hydroboration stereoselective synthesis of olefins
E-olefins
H. C. Brown, et al J. Org. Chem. 1989, 54, 6064.
78 Hydromagnesiation
F. Sato, Chem. Rev. 2000, 100, 2835; Synlett 2000, 753 79 Hydromagnesiation
O OH O Mg O EtMgBr CO2 Cp2TiCl2 cat.
90% O Me Bu Bu H OMgBr EtMgBr H OMgBr Bu
Cp2TiCl2 cat. O Me MgBr MgBr
EtCN + then H3O
O O
Bu Et Bu H Me Me
F. Sato, Chem. Rev. 2000, 100, 2835 80 Synthesis of aryl boronic acids transition-metal catalyzed synthesis of aryl boronic acids
O H B O or O O O B B B O O O Ir(OMe)(COD) 2 catalytic FG FG
Cl O O Br B Cl B Br O O
CO2Me CN CN CO2Me 83% 80%
J. F. Hartwig, N. Miyaura, Chem. Comm. 2003, 2924; J. Am. Chem. Soc. 2002, 124, 390; Angew. Chem. Int. Ed. 2002, 45, 3056 81 Synthesis of aryl boronic acids
M. Murata Tetrahedron Lett. 2000, 41, 5877 M. Murata Synth. Comm. 2002, 32, 2513
P. V. Ramachandran Org. Lett. 2004, 6, 481 82 Reactivity of unsaturated boronic derivatives
the Petasis-reaction - a short synthesis to 2H-chromenes
O
CHO HN O N Bu B(OH)2 Bu OH dioxane, 90 °C, 12 h OH 2,6-lutidine 90 °C, 30 min
dibenzylamine (5 mol%) 92 % dioxane, 90 °C, 12 h O R
83 Reactivity of unsaturated boronic derivatives
The Petasis-reaction mechanism
Bn Bn N CHO O R H OH
B(OH) Bn2N 3 Bn Bn N
O R OH B(OH)2 Bn Bn N R R
B (HO)2B O OH OH
M. G. Finn, Org. Lett. 2000, 2, 4063 84 ÜBUNG
1. Problem set
85 First Problem Set for OC IV
1) Give a mechanism for the following reactions:
O CO2H 1) TsNHNH Et 2 Et a) 2) 2 BuLi + Me 3) CO2, then H3O Me H I 1) t-BuLi (2 equiv.) b) I 2) THF H O H Et EtMgBr OH c) How would you prepare OH
O O Me d) 1) BuMgBr Me + 2) H3O Me OEt Bu Me 86 First Problem Set for OC IV
2) Give the following reaction products:
O Li Ph-CN A B a) then H O+ O 5% t-Bu t-Bu 3 Cl O Li PhCHO Me A b) N Cl 2 5% Me
H OMe BuLi CeCl3 c) A B H H THF, 0 °C O
s-BuLi MeI d) B stereochemie? TMEDA Me N O Ot-Bu
Et e) PhCH Li + A 2 Me Br H
H O f) BuMgBr + A 87 Me First Problem Set for OC IV MgBr + THF H3O HNEt2 g) + HC(OEt)3 A B C 25 °C NaBH4
MgBr MgBr S Me NC h) A B + O N ClTi(OiPr)3
CO2Et O 1) t-BuLi, -100 °C OMe 2) CO2 i) Me A + 3) H3O 4) CH2N2
BuLi 1) TsCl j) O A B . 2) Bu CuLi BF3 OEt2 2 -90 °C
1) BuLi, -100 °C k) NC Br A 2) O O
O 1) O 1) AlCl3 SH SH l) A B Hept Cl 2) H , Ni Raney 88 2) Et2Zn 2 First Problem Set for OC IV
3. How you would prepare following organometallics:
CO2Me NO2 O OMe MgBr MgCl O ICH2ZnI S Me Li OEt MgBr CN Ph N NO2 Cl Mg O ZnCl N N ZnCl EtO OEt N BF3 Boc ZnCl MgCl
O CO2Et Ph N Ph Ph NN
CO2Et MgCl MgCl.LiCl
89 The Suzuki cross-coupling reaction
1 2 1 2 2
N. Miyaura, A. Suzuki Chem. Rev. 1995, 95, 2457 Cross-Coupling Reactions. A practical guide. N. Miyaura (Ed.), Springer, 2002
Key step
S. Buchwald, J. Am. Chem. Soc. 2002, 124, 1162 C. Amatore, A. Jutand, G. Le Duc Chem. Eur. J. 2011, 17, 2492 B. P. Carrow, J. F. Hartwig J. Am. Chem. Soc. 2011, 133, 2116 90 The Suzuki cross-coupling reaction
R. E. Sammelson, M. J. Kurth, Chem. Rev. 2001, 101, 137
R1 R1 Cu(OAc)2 Ar-B(OH)2 + HN Ar N R2 Et3N R2 Pyr
D. A. Evans, Tetrahedron Lett. 1998, 39, 2937 S. Ley, Angew. Chem. Int. Ed. 2003, 42, 5400 91 Chemistry of allyl boranes
R. W. Hoffmann, Tetrahedron 1984, 40, 2219
92 Hydroalumination
H Al I Al(iBu) 2 I Bu H Bu 2 Bu OH 1) BuLi 2) RCHO Bu R
G. Zweifel, Org. React. 1984, 32, 375
93 Hydroalumination
Special Al-reagents
OH t-Bu t-Bu t-Bu toluene Me3Al + Me O Al Me MAD 2 t-Bu Me
H. Yamamoto J. Am. Chem. Soc. 1988, 110, 3588 H. Yamamoto Chem. Comm. 1997, 1585 94 Hydroalumination
Al HO Me O O O MeLi MeLi MAD Ph SiO Ph3SiO 3 Ph3SiO Ph3SiO Me
t-Bu
Me O Al Me 2 t-Bu MAD
K. Maruoka, H. Yamamoto, Kagaku, Zokan (Kyoto, Japan) 1988, 115,127 S. Nagahara, K. Maruoka, H. Yamamoto, Bull Chem Soc. 1993, 66, 3783
95 Hydroalumination
Verley-Meerwein-Ponndorf reduction
K. Maruoka Angew. Chem. 1998, 110, 2524 96 Other preparation of aluminium compounds
SnMe AlMe 3 heptane, 25 °C 2 + Me2Al-Cl + 2Me3SnCl SnMe3 AlMe2
K. Dimroth, Angew. Chem. Int. Ed. 1964, 3, 385
Direct synthesis of organoaluminium reagents
T. Blümke, Y.-H. Chen, Z. Peng, Nature Chem. 2010, 2, 313 97 Hydroalumination
Reactivity
T. Ishikawa, A. Ogawa, T. Hirao J. Am. Chem. Soc. 1998, 120, 5124
98 The organic chemistry of main-group organometallics
Silicium
The effect of a Me3Si-substituent:
1) inductive effect: weak donor-effect 2) retrodonation of -electrons (d-p bond) stabilization of carbanions in -position
3) hyperconjugation: interaction of -framework with the -system
R3Si
stabilization of a cation in -position
99 Silicium
Applications:
G. Stork J. Am. Chem. Soc. 1973, 95, 6152; 1974, 96, 6181 100 Silicium
Peterson olefination
D. J. Ager Synthesis 1984, 384
Stereochemistry of the Peterson-elimination
O H H Pr2CuLi Me3Si OH base syn elimination Pr Pr Me3Si Pr Pr Pr
H+ anti elimination
SiMe H Pr Me3Si O Pr CuLi 3 base 2 H OH syn elimination Pr Pr Pr Pr
P. F. Hudrlik, D. Peterson, R. J. Rona J. Org. Chem. 1975, 40, 2263 101 Silicium
key steps:
102 Reactivity of alkenylsilanes
L. E. Overman, Tetrahedron Lett. 1984, 25, 5739
103 Reactivity of alkenylsilanes
Sila-Nazarov-reaction
S. E. Denmark J. Am. Chem. Soc. 1982, 104, 2642
Aromatic ipso-substitution
3
3
4 The reaction with ArSnMe3 is 10 time faster 104 Allylic silanes in organic synthesis
General reactivity
Acylation
105 Allylic silanes in organic synthesis
Allylation
SiMe3 tBuCl, TiCl4
1,4-addition
O . O BF3 OEt2 + Me SiMe3 H Me Me
T.Yanami,M.Miyashita,A.Yoshikoshi,J. Chem. Soc. Chem. Commun. 1979, 525. T.Yanami,M.Miyashita,A.Yoshikoshi,J. Org. Chem. 1980, 45,607.
106 Indium
Element Cost in Euro/Mol In 167 Euro/Mol Mg 1,5 Euro/Mol Zn 3 Euro/Mol strong oxophilicity Li 10 Euro/Mol
The first ionization potential of indium (5,8 eV) is close to lithium and sodium
Key contributions:
S. Araki Main Group Metals in Organic Synthesis 2004, 1, 323 T.-P. Loh Acid Catalysis in Modern Organic Synthesis 2008, 1, 377 107 Indium. Allylation reactions
with H2O: 73% without H2O: 98%
S. Akira, J. Chem. Soc. Perkin Trans. I, 1991, 2395
OH Br CN In + R PhCHO H2O CN E:Z mixture
B. Manze, Synth. Commun. 1996, 26, 3179
108 Indium
T. P. Loh, J. Am. Chem. Soc. 2003, 125, 13042 109 Indium
OH Br In/H2O + PhCHO FF Ph 100% FF
OH Ph Sn, InCl3 Ph CF2Br + PhCHO H O Ph 2 FF 67%
In/H2O OH + PhCHO EtO2C Br Ph
CO2Et
without La(OTf)3: 59% anti:syn = 86 : 14 with La(OTf)3: 99% anti:syn = 90 : 10
L. A. Paquette, Tetrahedron Lett. 1999, 40, 4129 110 Indium
M. Lombardo, Pure Appl. Chem. 2004, 76, 657
T. H. Chan, J. Org. Chem. 1995, 60, 4228 111 Indium
OH In OH H + Br Ph Ph H2O:THF O HO Ph 90% > 98% ee
L. A. Paquette, Org. Lett. 2000, 2, 1263 112 Indium
Applications in nucleoside chemistry:
S. Kumar, Tetrahedron Lett. 2001, 42, 7039
O O 1) In2Br3
2) Ag2O O O O H
O H+
S. Akiva, J. Organomet. Chem. 1991, 415, 7 113 Indium
T. P. Loh, Tetrahedron Lett. 1997, 38, 865
P. Mosset Tetrahedron Lett. 1995, 36, 6055 P. Mosset Chem. Eur. J. 1997, 3, 1064 114 Indium
Applications in natural product syntheses:
CO2t-Bu CO2t-Bu O InI
AcO O O H Pd(PPh3)4 cat. HO Me Me
J. A. Marshall, J. Org. Chem. 1999, 64, 5193
S-K. Kang S-W. Lee J. Jung Y. Lim J. Org. Chem. 2002, 67, 4376 115 Indium
U. Lehmann, Org. Lett. 2003, 5, 2405
radical reaction
K. Oshima, Tetrahedron, 2003, 59, 6627 116 Early transition metal organometallics: Titanium
2 2 2 2 3 2 2 4
2 2 2
S. H. Pine Org. React. 1993, 43,1 117 Titanium
Lombardo-reagent
K. Takai, J. Org. Chem. 1994, 59, 2668
S. Buchwald, R. H. Grubbs J. Am. Chem. Soc. 1983, 105, 5490 118 Titanium
T. Livinghouse, J. Am. Chem. Soc. 1992, 114, 5459
119 Titanium
Hydrotitanation
T. Takeda, Tetrahedron Lett. 1985, 26, 5313
120 Titanium
Reductive coupling: The McMurry Reaction
Review: A. Fürstner, Ed. M. Beller, C. Bolm, Transition Metals for Organic Synthesis (2nd Edition) 2004, 1, 449.
121 Titanium
-Caroten: 94%
J. E. McMurry et al. J. Am. Chem. Soc. 1984, 106, 5018.
122 Titanium
Kulinkovich-reaction
O. G. Kulinkovich, S. V. Sviridov, D. A. Vasilevskii, T. S. Pritytskaya, Zh. Org. Khim. 1989, 25, 2244. O. Kulinkovich, S.V. Sviridov, D.A. Vasilevski, Synthesis, 1991, 234.
123 Titanium
SiMe3 SiMe3 SiMe 3 EtMgBr, Ti(OiPr)4 Ti(OiPr) Me 4 Me Ti(OiPr)2 Me Ti(OiPr)2 CO Et 2 CO2Et OEt (iPrO)2Ti O
SiMe3 SiMe3 SiMe3 + H3O Me O Me O Me Ti(OiPr)3 Ti(OiPr)3 C O
F. Sato J. Org. Chem. 1988, 53, 5590.
124 Early transition metal organometallics: Zirconium
Schwartz’s reagent:
Inorg. Synth. 1979, 19, 223
125 Zirconium
G. I. Georg J. Am. Chem. Soc. 2007, 129, 3408
126 Zirconium
A Negishi reaction is involved:
127 Early transition metal organometallics: Chromium
Hiyama reaction Bull. Soc. Chem. Jpn 1982, 55, 567; J. Am. Chem. Soc. 1977, 99, 3175 128 Chromium
2
2
K. Belyk, M. J. Rozema, P. Knochel J. Org. Chem. 1992, 57, 4070.
129 Chromium
Hiyama-Kishi-reaction
I O NiCl (1 mol%) 2 Ph Ph H 2CrCl 2 OH CrCl DME Ni(0) 2
Ni2+ O
Ni I Ph H
CrCl2
CrCl3
TDPSO OH TDPSO H CHO NiCl2 (1 mol%) I 2CrCl2,DMS,DMSO O Me O Me 56%
Y. Kishi J.Am.Chem.Soc. 1989, 111, 2735. 130 Chromium
2 3
2 2 2 2
2 1 2 1
2
K. Takai J. Am. Chem. Soc. 1986, 108, 7408 131 Early transition metal organometallics: Copper
S S Li Cl Cl R R Me CHO 1) Me2CuLi CHO R2CuLi Cu Cu 2) H+ 73% R Li R S S
1)Zn,THF,60°C O EtO C I EtO2C 2 2) CuCN . 2LiCl 94% 3) O
Me3SiCl (2 equiv.) 1)Zn,THF,60°C . 2) CuCN 2LiCl EtO2C Cu(CN)ZnX
P. Knochel, et al. J. Org. Chem. 1988, 53, 2390.
132 Copper
CO2Et SiMe Ph 2Li CuI Me 2 2PhMe SiCl 2PhMe SiLi (PhMe2Si)2CuLi CO Et 2 2 Me 2
81% I. Fleming et al. J. Chem. Soc., Perkin Trans. 1998, 1, 1209.
O O
1) Bu2CuLi
+ Me Me 2) H Bu without additives: 28% Me3SiCl (2 equiv.): 99% E. Nakamura et al. Tetrahedron Lett. 1986, 27, 4029.
133 Copper-mediated 1,4-addition
O
Me3SiCl Pr Cu O
Pr
O O MeCu BF3
Me Me Me 77%
Y. Yamamoto, Angew. Chem. 1986, 98, 945.
134 Copper-mediated reactions
135 Copper; substitution reactions
Me Oct2CuLi Me OBn TsO OBn SN2 inversion Oct 73%
H Me CuLi OH O 2 Me Me CO2Et CO2Et Me 90%
Li2CuCl4 tBuMgCl + PhCH2Cl PhCH2tBu 0.25 mol%
M. Larcheveque, Y. Petit, Bull. Soc. Chim. Fr. 1989, 1, 130.
136 Copper: allylic and propargylic substitution
3 3
Pure Appl. Chem 64 137 Copper: Prostaglandin synthesis
F. Sato J. Org. Chem. 1988, 53, 5590
138 Palladium
Price of Pd: 1.0 Pt: 3.3 Au: 1.9 Ru: 0.2 Rh: 2.8
Wacker-Reaction:
H2CCH2 + H2O + PdCl2 CH3CHO + 2 HCl + Pd(0)
Pd(0) + 2CuCl2 PdCl2 + 2CuCl 2CuCl 1 + 2 HCl + /2 O2 2CuCl2 + H2O
O 1/ O R + 2 2 R
J. Schmidt, W. Hafner, R. Jira, R. Sieber, J. Sedlmeier, J. Sabel, Angew. Chem. Int. Ed. 1962, 1, 80.
139 Palladium
O O H PdCl2, CuCl NaOEt O H2O, DMF O
68% 85%
J. Tsuji, I. Shimizu, K. Yamamoto, Tetrahedron Lett. 1976, 34, 2975.
140 Palladium C-H activation
PdOAc
+ Pd(OAc)2 Ph Ph + Pd(0) -HOAc
Ph Pd(OAc)2 + Ph H O CHO (1 equiv.) O CHO 48% T. Itahara, J. Org. Chem. 1985, 50, 5272.
O O
HN HN CO Bu 5% Pd(OAc)2 2 + CO2Bu O O 85% AcOH
J. G. de Vries J. Am. Chem. Soc. 2002, 124, 1586. 141 Palladium
Heck Reaction
Br IMes,HCl,Pd(OAc)2 CO2Bu + CO2Bu Me MeCONMe2, 120 °C Me
Cl NN Mes Mes The method of T. Jeffery uses Bu4NBr at 25 °C. IMes T. Jeffery Chem. Comm. 1984, 1287
142 Palladium-catalyzed cross-coupling
Cross-coupling using Pd(0)-catalysts
R1 PdLn R2-Met R1-X X Suzuki-coupling Met = B(OH)2
Stille-coupling Met = SnR3 Negishi-coupling Met = ZnX PdLn R1 MetLn R2 Kumada-coupling cat = Ni; Met = MgX
Sonogashira-coupling Csp-Csp2
R1-R2
143 Palladium
144 Palladium
2 t 2
t t t 2 3, t 2 2
Angew. Chem. Int. Ed 40
145 Palladium
O 3% PdCl2(dppf) O BH + IMe B Me O dioxane, 80 °C, 1h O
79 %
M. Murata, J. Org. Chem. 2000, 65,164.
1. 9-BBN-H, THF 2. 3N NaOH NHCbz NHCbz Ph PhI, 10% PdCl2(dppf) 86 % 25 °C, 1h
L. E. Overman, J. Org. Chem. 1999, 64, 8743.
146 Palladium
Bu Sn (1.05 equiv) Cl 4 Bu 1.5% Pd2(dba)3
MeO 6% t-Bu3P MeO CsF, dioxane, 100 °C, 48 h 82%
G. C. Fu, Angew. Chem. Int. Ed. 1999, 38, 2411.
On the mechanism of the Stille cross-coupling:
P. Espinet J. Am. Chem. Soc. 1998, 120, 8978. J. Am. Chem. Soc. 2000, 122, 1771.
147 Palladium
148 Negishi reactions
Synthesis of carotenoids via Zr-catalyzed carboalumination and Pd /Zn-catalyzed cross-couplings:
HBr Me Si ZnBr Br 3 HC CH I Me3Si IBr 2% Pd(PPh3)4 Br 0°C,48h 76 % 0-23 °C, 14 h 1:81%
1) Me3Al (2 equiv) 1) LDA, THF Cp ZrCl (1 equiv) O 2 2
2) ClP(O)(OEt)2 ClCH2CH2Cl, 23 °C, 4 h 3) LDA (2.2 equiv) 2) ZnCl2, 5% Pd2dba3 2:70% 85 % 5% (o-furyl)3P, 1 DMF, 23 °C, 6 h 3) K2CO3, MeOH, 23 °C, 3 h
1) Me3Al-Cl2ZrCp2 2
2) ZnCl2, Pd(0) Br I ,DMF 23 °C, 8 h ß-carotene: 68%; >99% isomeric purity
E. Negishi, Org. Lett. 2001, 3, 719. 149 Palladium
Example of an indole synthesis via an intramolecular cyclization of alkynes and imines using a Pd-catalyst:
150 Palladium
M. S. McClure, Org. Lett. 2001, 3, 1677 151 Palladium
Pd - catalyzed hydroamination of vinylarenes
H. Hartwig J. Am. Chem. Soc. 2000, 122, 9546 152 Palladium
Pd -catalyzed heterocycle synthesis
Ph OMe NPh MeO 5% Pd(OAc)2 N Bu I i-Pr2NEt (2 equiv) Bu NCl (1 equiv) 4 Bu DMF, 100 °C, 36 h 78 %
R.C. Larock, J. Org. Chem. 2001, 66, 412 153 State of the art
N N Mo Br Me
TBSO O Ph Me
Br
catalyst (2.5 mol%) Ph OBu OBu + Ph benzene, 22 °C 73%; Z:E > 98:2
A. H. Hoveyda, Nature 2011, 471, 461 A. H. Hoveyda, Nature 2008, 456, 933 154 Olefin metathesis
Mo or Ru-catalyst R1 R2 R1 R2 + + R 4 R3 R4 R3
Reviews:
R.H. Grubbs, Tetrahedron 1998, 54, 4413. A.S.K. Hashmi, J. Prakt. Chemie 1997, 339, 1954. M.E. Maier, Angew.Chem.Int.Ed. 2000, 39, 2073. S.Blechert, Angew. Chem. 1997, 109, 2124. A.Fürstner, (Ed.) Alkene Metathesis in Organic Synthesis in Top. Curr. Chem., Springer Verlag, Berlin, 1998. E.M. Carreira, Synthesis 2000, 857. Mechanistic study: R.H. Grubbs, J. Am. Chem. Soc. 2001, 123, 749. 155 Olefin metathesis mechanism
Mo or Ru-catalyst R1 R2 R1 R2 + +
R4 R3 Ru R4 R3 A 5% catalyst
R2 R R R1 1 1 R Ru Ru Ru R3 3 Ru A R4 R4 A R2 R1 R4 A R1
R4 R3 Ru R4 R3
R1 R2 156 Olefin metathesis
157 Olefin metathesis
PCy3 Cl Ph Tos Ru Tos 3 (5 mol%) N Cl N NN CH2Cl2,40°C,16h
80 % 3
A. Fürstner, W.A. Herrmann, Tetrahedron Lett. 1999, 40, 4787
158 Olefin metathesis
Synthesis of -unsaturated amides by olefin cross-metathesis
R. H. Grubbs, Angew. Chem. Int. Ed. 2001, 40, 1277 159 Olefin metathesis
New phosphine-free metathesis catalyst
PCy3 PCy O 3 CHCl3 Cl2Ru catalyst Cl2Ru 25 °C, 2 h Mes Cl Ru O t-BuOK 2 N O THF / toluene N Mes Mes Mes 80 °C, 1 h NN
catalyst Ts Ts N N catalyst (5 mol%)
15 min, rt 100 %
S. Blechert, Tetrahedron Lett. 2000, 41, 9973 160 Application to the synthesis of natural products
Synthesis of aza sugars
S. Blechert, Org. Lett. 2000, 2, 3971 161 Olefin metathesis
Synthesis of complex ring-systems via metathesis
1) Bu3Sn H H Bu3Sn OMe O H H H MgBr2 H H OH O O O O O O OAc H OO CSA, CH2Cl2,rt MS 4A° HH2 OO H O 2) DIBAL, -78 °C HH2 H H 3) Ac2O, Pyr 73 %
PCy3Ph ds > 95 : 5 Cl2Ru PCy3
(20 mol%)
H O H H O O O H H H 91 %
Y. Yamamoto, J. Am. Chem. Soc. 2001, 123, 6702 162 Olefin metathesis
Cross-/ self-metathesis with allylsilanes
S. Blechert, Chem. Eur. J. 1997, 3, 441.
Cross-metathesis with allylic silyl ethers: A.G.M. Barrett, Chem. Commun. 1996, 2229 and 2231
Cross-metathesis with fluorinated olefins: S. Blechert, Chem. Commun. 2001, 1692 163 Olefin metathesis
Synthesis of jasmonic acid derivatives
S. Blechert, Chem. Eur. J. 1997, 3, 441 S.E. Gibson, Chem. Commun. 1997, 1107 S. Blechert, Chem. Commun. 1997, 1949 164 Olefin metathesis
Cross-metathesis of alkynes with ethylene
S.T. Diver, J. Org. Chem. 2000, 2, 1788 165 Olefin metathesis
Ru-catalyzed Ring-Opening and –Closing Enyne Metathesis
Ts Ts N N Cl2Ru(PCy3)2=CHPh cat.
TBDMSO TBDMSO H2CCH2
CH2Cl2,rt,5h 95 %
Ts Ts N N Cl2Ru(PCy3)2=CHPh cat. 90 % TBDMSO TBDMSO H2CCH2
CH2Cl2,rt,5h Ru CH 2 H2CCH2
Ts Ts N N
RO RO Ru Ts Ts Ru N N
RO Ru RO Ru
M. Mori, Org. Lett. 2001, 3, 1161 166 Olefin metathesis
A double ring closing metathesis for the synthesis of NK-1 receptor antagonists
Merck-team Org. Lett. 2001, 3, 671 167 New C-H activation reactions
D D D [M] R H H M H C C C R
E+ CO
D D E CHO C C
Book: S. Murai, (Ed.) Activation of Unreactive C-H Bonds in Organic Synthesis, Topics in Organometallic Chemistry, Springer, 1999. 168 The Murai-reaction
O O Me Me RuH2(CO)(PPh3)2 cat. Si(OEt) + 3 toluene N N Si(OEt)3 Me Me 76 %
R. Grigg, Tetrahedron Lett. 1997, 38, 5737 S. Murai, Nature, 1993, 366, 529 S. Murai, J. Organomet. Chem. 1995, 504, 151 169 The Murai-reaction
Ru-mediated synthesis of 4-acylated imidazoles via C-H-activation
Ph Ph Me N '' + OO N N Me O O N O 72 %
'' N + OMe OMe N N OMe N OMe O 90 %
S. Murai, J. Am. Chem. Soc. 1996, 118, 493 170 Annulation of heterocycles via a Rh-catalyzed C-H-activation
R. G. Bergman, J. Ellman, A. J. Am. Chem. Soc. 2001, 123, 2685 171 The catalytic hydroacylation of alkenes
Mechanism:
CH3 CH3
N N N N R1 R2CHO -L 2 ClRh 2 -L R R CH3 L2 H
N N CH3 L3RhCl ClRh R2 N NH2 L H
L 1 L R CH3 CH3
O N N N N 2 1 ClRh R R R1 R2 R2 L2 R1
Review: C.-H. Jun, Synlett, 1999, 1 172 C.-H. Jun, Org. Lett. 1999, 1, 887; Tetrahedron Lett. 1997, 38, 6673; J. Org. Chem. 1997, 62, 1200 Gold-catalyzed organic reactions
Nucleophilic addition to C-C multiple bonds
For a review see: A. S. Hashmi, Chem. Rev. 2007, 107, 3180 173 Gold-catalyzed organic reactions
Nucleophilic addition to C-C multiple bonds:
Au3+-catalyzed cyclization followed by a Prins type cyclization
For a review see: A. S. Hashmi, Chem. Rev. 2007, 107, 3180 174 Gold-catalyzed organic reactions
Gold(III)-triggered rearrangements
175 Gold-catalyzed organic reactions
Au3+-initiated cycloadditions
H R3 O R4 3mol%AuCl3 O R2 R3 O R1 R1 R1 DCE, 80 °C [Au] [Au]
R3
R2
O R1 57-96%
Y. Yamamoto, J. Am. Chem. Soc. 2003, 125, 10921 176 Gold-catalyzed organic reactions
Use of electrophilic Gold(I)-complexes: Ph3P-Au-OTf
t-Bu O t-Bu t-Bu O 5mol%Ph3P[Au]OTf O O O O Bu MeCN, 25 °C [Au] Bu Au Bu
t-Bu t-Bu O O O O O H3O -Au [Au] Bu Bu Bu 85%
F. D. Toste J. Am. Chem. Soc. 2005, 127, 5802 177 Gold-catalyzed organic reactions
Intramolecular phenol synthesis
A. S. Hashmi, J. Am. Chem. Soc. 2000, 122, 11553 178 Gold-catalyzed organic reactions
Asymmetric aldol reaction
O O 1 mol% Au(CN-Cy)2BF4 C L* X N O + N R X CH Cl ,25°C O 2 2 R
86-97% Ph Ph trans : cis up to 93 : 7 H up to 94% ee P O Fe Au R P OH Ph Ph N H X H H N Me N O
T. Hayashi J. Am. Chem. Soc. 1986, 108, 6405 179