D.A. Evans Olefin Addition Reactions: Part-2 Chem 206 Other Reading Material http://www.courses.fasharvard.edu/-chem206/ Takaya, H, T. Ohta, et al. (1993). Asymmetric Hydrogenation Catalytic Asymmetric Synthesis. L Ojima. New York, VCH: 1-39 Chemistry 206 Bolm, C (1993)." Enantioselective transition metal-catalyzed hydrogenation for the asymmetric synthesis of amines. Angew. Chem., Int. Ed Engl. 32: 232 Advanced Organic Chemistry For a recent general review of the Simmons-Smith reaction see Lecture number 9 Charette& Beauchemin, Organic Reactions, 58, 1-415(2001) Problems of the Day: (To be discussed Olefin Addition reactions-2 Epoxidation& Directed Epoxidation Predict the stereochemical outcome of the indicated reaction Hydrogenation Hydride Reduction L2, NaHCO3 Reading Assignment for week Kinetic Control: 3 eq I2, MeCN, NaHCO3, 0-C A. Carey Sundberg: Part B; Chapter 4 diastereoselection: 20: 1 Electrophilic Additions to C-C Multilple Bonds Bartlett, P. A; Richardson, D. Myerson, J. Tetrahedron 1984, 12, 2317 K.Houk, Science.1986,231,1108-1117 Theory Modeling of Stereoselective Organic Reactions(Handout) Rationalize the stereochemical outcome of the indicated reaction Houk. Tetrahedron. 1984. 40. 2257-2274 Theoretical Studies of stereoselective Hydroboration Reactions Hoveyda, Evans, Fu(1993). Substrate-directable chemical reactions. Chem. Rev. 93: 1307-70(Handout) Monday, Matthew d shair October 7. 2002 Bull. Chem. Soc. Japan 47, 2617, (1974) LiAIH4
http://www.courses.fas.harvard.edu/~chem206/ Me Me HOOC Me I2, NaHCO3 N Me O OH N M–H Me H LiAlH4 R2AlH O O Me Me Me I N Me H OH D. A. Evans Chem 206 Matthew D. Shair Monday, October 7, 2002 ■ Reading Assignment for week A. Carey & Sundberg: Part B; Chapter 4 "Electrophilic Additions to C–C Multilple Bonds" Olefin Addition Reactions: Part–2 Chemistry 206 Advanced Organic Chemistry Lecture Number 9 Olefin Addition Reactions–2 K. Houk, Science. 1986, 231, 1108-1117 Theory & Modeling of Stereoselective Organic Reactions (Handout) ■ Epoxidation & Directed Epoxidation ■ Hydrogenation ■ Hydride Reduction K. Houk, Tetrahedron. 1984, 40, 2257-2274 Theoretical Studies of Stereoselective Hydroboration Reactions (Handout) Hoveyda, Evans, & Fu (1993). Substrate-directable chemical reactions. Chem. Rev. 93: 1307-70 (Handout) ■ Problems of the Day: (To be discussed) ■ Other Reading Material Takaya, H., T. Ohta, et al. (1993). Asymmetric Hydrogenation. Catalytic Asymmetric Synthesis. I. Ojima. New York, VCH: 1-39. Bolm, C. (1993). “Enantioselective transition metal-catalyzed hydrogenation for the asymmetric synthesis of amines.” Angew. Chem., Int. Ed. Engl. 32: 232. diastereoselection: 20:1 Predict the stereochemical outcome of the indicated reaction. Bartlett, P. A.; Richardson, D.; Myerson, J. Tetrahedron 1984, 12, 2317 Kinetic Control: 3 eq. I2 , MeCN, NaHCO3 , 0°C R. Noyori Bull. Chem. Soc. Japan 47, 2617, (1974) 28 : 72 97 : 3 Rationalize the stereochemical outcome of the indicated reaction. For a recent general review of the Simmons-Smith reaction see: Charette & Beauchemin, Organic Reactions, 58, 1-415 (2001)
D.A. Evans Directed Reactions: An Introduction Chem 206 Stereochemical control elements for all reactions Heteroatom-directed Reactions Steric Electronic Factors Mechanism-based(HO&C=C must be allylic Stereoelectronic Considerations I Associative Substrate-Reagent Interactions ■ Steric control: A-B disfavored favored product A-B vored Nonbonding Interactions disfavor the syn diastereoface Simmons-Smith Reaction Directed Reactions Hydroxyl-directed Reactions Review. Hoveyda, Evans, Fu Chem. Reviews 1993, 93, 1307 tio 92: 8 Associative Substrate-Reagent Interactions A-B A-B -BUOoH Sharpless vo(acac)2 JACS95,6136,(1 favored product disfavored Noncovalent Interaction favors the syn diastereoface A-B Directed Oxidations OH JACS 91, 6892. (1969) ratio 90: 10 Directed Reductions Hydrogenation Hydride reduction AcS105,1072(1983) Directed c-c Bond constructions Acs1063866(1984
X R A B A B X A B R B A X B A A B C C H H H C C H H H A B A B A B OH OH R R OH MCPBA Et2Zn Cl CO3H t-BuOOH Et2Zn CH2I2 OH Me CH2 I2 R O CH2 R O Zn CH2 I R H OH O Me OH CH2 OH R R O CH2 OH R (Ir+ ) Stork JACS 105, 1072 (1983) (Rh+ ) Evans JACS 106, 3866 (1984) M(I) + H2 Mechanism-based: (HO & C=C must be allylic) Simmons-Smith Reaction Claisen Rearrangement [3,3] via Reagent Ligation Heteroatom-directed Reactions ratio 90 : 10 Winstein JACS 91, 6892, (1969) Henbest J. Chem. Soc. 1958, (1957) Sharpless VO(acac) JACS 95, 6136, (1973) 2 ratio 98 : 2 ratio 92 : 8 Hydroxyl-directed Reactions Directed C–C Bond Constructions Directed Reductions Hydrogenation Hydride reduction Epoxidation Hydroboration Directed Oxidations Agenda Directed Reactions favored disfavored favored product ■ Associative Substrate-Reagent Interactions Noncovalent Interaction favors the syn diastereoface Review: Hoveyda, Evans, Fu Chem. Reviews 1993, 93, 1307 ■ Steric control: Stereochemical Control Elements for all reactions ■ Steric & Electronic Factors ■ Stereoelectronic Considerations ■ Associative Substrate-Reagent Interactions favored product favored disfavored Nonbonding Interactions disfavor the syn diastereoface D. A. Evans Directed Reactions: An Introduction Chem 206
D. A. Evans Directed Reactions: An Introduction Chem 206 Orientation of the Directing Group A Rao in Comprehensive Organic Synthesis, Trost, Ed, 1992, Vol 7, Chapter 3.1 ■ General reaction HOMO LUMO note labeled oxygen is 00 I Transition state: What about lone pairs. [Consider o to be Sp- hybridized] Orientation of directing group is not the same for all reactons HOMO IC-C HOMO: o lone pair LUMO: g*0-0 LUMO: T*C-C t-Buo2H. V a Reaction rates are govemed by olefin nucleophilicity. The rates of epoxidation of the indicated olefin relative to cyclohexene are provided RCO3H 95:5 CH2l2, Zn-Cu 99:1 he transition state bite angles for the above reactions are either not known or have been only crudely estimated. a The indicated olefin in each of the diolefinic substrates may be oxidized The best guesses"are provided
OH R O O O R R R R ● ● O O H O R O O H O R •• •• •• ● ● ● •• ● Me Me OH H H C OH H Me C H Me H RCO3H Me Me OH X C H Me C OH Me H H C H C H R R R R R R Me Me Me O R O O H C R C R H H OH Me Me O R O O H C R C H H OAc OH H Me Me Me Me C R C H H O R OH D. A. Evans Directed Reactions: An Introduction Chem 206 Orientation of the Directing Group ? ~ 120 ° ~ 50 ° > 99 : 1 95 : 5 71 : 29 CH2I2, Zn–Cu Reagent Selectivity F Estimate reagent t-BuO2H, V +5 X = O, CH2 Reag Reag Æmaj Æmin ‡ ‡ TSmajor TSminor The transition state bite angles for the above reactions are either not known or have been only crudely estimated. The "best guesses" are provided. Orientation of directing group is not the same for all reactons Peracid Epoxidation LUMO note labeled oxygen is transferfed s*O–O ■ General Reaction: + + HOMO pC–C ■ Reaction rates are governed by olefin nucleophilicity. The rates of epoxidation of the indicated olefin relative to cyclohexene are provided below: ■ The indicated olefin in each of the diolefinic substrates may be oxidized selectively. 1.0 0.6 0.05 0.4 ■ Transition state: What about lone pairs. [Consider ● to be Sp2 hybridized]. O-O bond energy: ~35 kcal/mol A. Rao in Comprehensive Organic Synthesis, Trost, Ed., 1992, Vol 7, Chapter 3.1 HOMO pC–C LUMO: s*O–O HOMO: O lone pair LUMO:p* C–C
D. A. Evans Diastereoselective Peracid Epoxidation Chem 206 Stereoelectronic Implications of intramolecular Peracid Epoxidation The Directed Peracid Epoxidation a Transition State Hydrogen Bonding: Substrate as H-bond donor(Henbest I Per-arachidonic acid Epoxidation: Corey, JACS 101, 1586(1979) a Transition State Hydrogen Bonding: Peracid as H-bond donor(Ganem R-O require more acidic peracid both allylic alcohols and ethers OK 50:1 5:1 OTBS 1:8 OTBS 1:4 Me,C Ganem Tet. Let. 1985. 26. 4895
O R O O H O C H C H2 O C H R R O H O R O C C C H2 H R H R O CF3 O O H O C H C H2 O R C H R O O H O CF3 C H2 R O C H C H R •• •• R O O O H O O H O H C R R C H C H2 O C R C R H C H2 O H O H O CF3 OH OTBS OH Me3C Me3C OTBS O H O O Me3C OH OTBS Me3C ● ● 1 : 7 5 : 1 1 : 8 12 : 1 100 : 1 1 : 4 1 : 6 24 : 1 100 : 1 5 : 1 24 : 1 50 : 1 Syn : Anti (CF3CO3H) Syn : Anti (m-CPBA) Syn : Anti (m-CPBA) Syn : Anti (CF3CO3H) Ganem Tet. Let. 1985, 26, 4895 require more acidic peracid both allylic alcohols and ethers OK require allylic or homoallylic alcohol ■ Transition State Hydrogen Bonding: Peracid as H-bond donor (Ganem) ‡ ‡ ■ Transition State Hydrogen Bonding: Substrate as H-bond donor (Henbest) The Directed Peracid Epoxidation D. A. Evans Diastereoselective Peracid Epoxidation Chem 206 ■ Per-arachidonic acid Epoxidation: Corey, JACS 101, 1586 (1979) Stereoelectronic Implications of intramolecular Peracid Epoxidation ● ● ● ●
D. A. Evans Diastereoselective Peracid Epoxidation Chem 206 Epoxidation of Cyclic Olefins with Amide Urethane Directing Groups Epoxidation of Cyclic Homoallylic Alcohols Substrate Major Product lectivity Substrate Product Selectivity selective selective r aR= NH2 bR= NH CR= NMe2 ar=ocoNHBn >20: 1 bR=OCONMe? >20 a r= conh 6:1 5:1 bR= CONHE Conditions: Perbenzoic acid, or meta-chloroperbenzoic acid onditions: perbenzoic acid. or meta-chlorobenzoic acid in benzer n benzene or cyclopentane (Table 11, p1316, from the Evans, Hoveyda, Fu review article) (able 14, p1318, from the Evans, Hoveyda, Fu review article)
Conditions: Perbenzoic acid, or meta-chloroperbenzoic acid in benzene or cyclopentane. O HN Ph O HN Ph O HO HO HN Me O O HN HO HO Me O O R O O O R O Me R R Me O AcO RO AcO O RO OH O OH Me Et Me HO OH OH HO O Et Me Me HO Me O HO Me O Me HO O Me HO Me HO Me HO AcO HOH2C O AcO HOH2C (Table 14, p1318, from the Evans, Hoveyda, Fu review article) Major Selectivity Product Substrate 9 : 1 "highly selective" 16 : 1 1 : 1 5 : 1 21 : 1 Epoxidation of Cyclic Homoallylic Alcohols (Table 11, p1316, from the Evans, Hoveyda, Fu review article) Conditions: Perbenzoic acid, or meta-chlorobenzoic acid in benzene. "highly selective" "highly selective" Substrate Major Product Selectivity 10 : 1 3 : 1 5 : 1 a. R = NH2 b. R = NHBn c. R = NMe2 >20 : 1 >20 : 1 a. R = OCONHBn b. R = OCONMe2 a. R = CONH2 6 : 1 b. R = CONHBn c. R = CONMe2 >10 : 1 2 : 1 Epoxidation of Cyclic Olefins with Amide &Urethane Directing Groups D. A. Evans Diastereoselective Peracid Epoxidation Chem 206
D. A. Evans Sharpless Epoxidation(V+5) Chem 206 The Sharpless Epoxidation I The literature precedent: Sheng, Zajecek, J. Org. Chem. 1970, 35, 1839 少TBFP VO(acac)2 -ROH ROOH I Next step: Sharpless, Michaelson JACS 1973, 95, 6136 VO(acac)2 80°c Aldrichimica Acta, 12, 63 (1979) Mo(CO)6 0-C2-C3C4=41° The Sharpless estimate: -50% Relative Rates(Diastereoselectivities) for the Epoxidation of Cyclohexene Derivatives JACS 1973, 95, 6136 t-BuOOH Substrate peracid Mo(CO)6 VO(acac)2 10 055(92:8)45(98:2)>20098:2) tBu Chem 3D Transition State 042(60:40)110(98:2)10.0(98:2) a. b The relative rate data apply only to a given column Values in parenthesis refer to the ratio of syn anti epoxide
4 3 2 1 Relative Rates (Diastereoselectivities) for the Epoxidation of Cyclohexene Derivatives JACS 1973, 95, 6136 OH O O Me OH Me Me OH O Mo(CO)6 TBHP OH ROOH O V OR O O RO O O V OR O-OtBu O HO V O O O O RO tBu O HO OH Me Me Me OH OAc OH OH OH O Mo(CO)6 Mo(CO)6 t-BuOH RDS HO O tBu V RO O O O O OR V RO O OR O O V RO O HO R –ROH HO O O V O RO OR a,b The relative rate data apply only to a given column. Values in parenthesis refer to the ratio of syn:anti epoxide. krel a,b (diastereoselectivityc ) 11.0 (98 : 2) 10.0 (98 : 2) 0.07 (40 : 60) -- 4.5 (98 : 2) >200 (98 : 2) 1.00 1.00 0.42 (60 : 40) 0.046 (37 : 63) 0.55 (92 : 8) 1.00 Substrate VO(acac) peracid 2 80 °C Stereoselection 98:2 TBHP (90 % yield) ■ Next step: Sharpless, Michaelson JACS 1973, 95, 6136 Regioselection 20:1 80 °C TBHP VO(acac)2 ■ The literature precedent: Sheng, Zajecek, J. Org. Chem. 1970, 35, 1839 VO(acac)2 4 : 1 80 oC 1 : 1 Catalyst t-BuOOH slow Chem 3D Transition State Aldrichimica Acta, 12, 63 (1979) O–C2–C3–C4 = 41° The Sharpless estimate: ~50° The Sharpless Epoxidation + D. A. Evans Sharpless Epoxidation (V+5) Chem 206 ● ● ● ● ● ● ● ● ●
D. A. Evans Epoxidation of Acyclic Alcohols Chem 206 ■ Allylic Alcohols erythro m-CPBA Φ Estimate Reagent t-BuOOH/VO(acac)2 t-BuOOH/Mo(CO)6 62:38 120° m-CPBA 4050° t-BuOOH/ vO(acac)2 t-BuoOH / Mo(CO)6 ■RCo3 H Transition States:-120° -H Tsminor R2 Yield Ratio Oshima. Tetrahedron Lett 1982. 23 3387. HBu84%99:1 70%99:1 ■v(+) Transition States:Φ-45 MAjor 60% Eto OEt Eto OE threo Depezay, Tetrahedron Lett. 1978, 19, 2869 Ratio K Oshima Coworker O(acac)2 t-BuooH/VO(acac 86:14 Boeckman JACS 1977. 99. 2805 K B Sharpless Coworkers Tetrahedron Lett. 1979. 20. 4733 t-BuOOH/t-BUO)3Al 100:0 Me NHCONHPh NHCONHPh le NHCONHPh CH2Ch, 0C Roush, J.Org. Chem. 1987, 52, 5127 Diastereoselection= 95: 5
Me OH Me Me Me Me OH C Me H C H Me C Me H OH C HO H Me H H O Me Me OH Me Me OH Me O C H Me C Me H C Me H OH C HO H Me Me OH Me O Me O Me Me OH H H Me Me OH R1 R2 SiMe3 OH OEt OH O O EtO Me Me Me Me O EtO O OH OEt OH Me HO t-BuOOH t-BuOOH t-BuOOH H OH Me Me O C5H11 OH SiMe3 R1 R2 O O NHCONHPh Ph Me Me Ph NHCONHPh O OEt OH O O EtO Me Me Me Me O EtO O OH OEt O Bu Me HO Me OH O O Me Me OH O R1 R2 SiMe3 OH Ph NHCONHPh O Me Reagent + t-BuOOH / (t-BuO) 64 : 36 3Al 29 : 71 64 : 36 t-BuOOH / VO(acac)2 m-CPBA Reagent Ratio t-BuOOH / Mo(CO)6 62 : 38 ■ Allylic Alcohols: D. A. Evans Epoxidation of Acyclic Alcohols Chem 206 ~ 120 ° 40-50 ° F Estimate 71 : 29 95 : 5 t-BuOOH / VO(acac)2 m-CPBA Reagent Ratio t-BuOOH / Mo(CO)6 84 : 16 threo erythro Reagent + ■ RCO3H Transition States: F ~ 120 ° TSminor TSmajor ■ V(+) Transition States: F ~ 45 ° TSminor TSmajor K. B. Sharpless & Coworkers Tetrahedron Lett. 1979, 20, 4733. K. Oshima & Coworkers Tetrahedron Lett. 1980, 21, 1657, 4843. t-BuOOH / (t-BuO) 100 : 0 3Al 86 : 14 95 : 5 t-BuOOH / VO(acac)2 m-CPBA Reagent Ratio t-BuOOH / Mo(CO)6 95 : 5 + Reagent threo erythro 70 % 84 % R Yield 1 99 : 1 99 : 1 R2 Ratio + VO(acac)2 Oshima, Tetrahedron Lett. 1982, 23, 3387. Depezay, Tetrahedron Lett. 1978, 19, 2869. only isomer VO(acac)2 60 % 60 % t BuOOH VO(acac)2 only isomer Boeckman, JACS 1977, 99, 2805. Diastereoselection = 7 : 1 60 % VO(acac)2 Roush, J. Org. Chem. 1987, 52, 5127. m-CPBA CH2Cl2 , 0 °C 75 % + Diastereoselection = 95 : 5 ● ● ● ● ● ● ● ● ● ● ● ● ●
D. A. Evans Epoxidation of Acyclic Homoallylic Alcohols Chem 206 Homoallylic Alcohols(Mihelich, JACS 1981, 103, 7690 Anti diastereomer t-BUOOH Control Elements Diastereoselection > 400: 1 R2 A(1, 3)Strain Me92%104:1 Syn diastereomer 97% R2 t-BuOoH 73%70 Me 81% Diastereoselection 12: 1 ontrol Elements Directed rxn H E D. Mihelich& Coworkers Diastereoselection= 211: 1 J.Am.chem.Soc1981,103,7690. Epoxidation of Homoallylic Alcohols with TBHP, VO(acac)2 Predictio Substrate Product Anti should be more diastereoselective than syn Anti diastereomer Syn diastereo
H O R Me H H V O Me O L H H H V O L O O Et H H R Me V O R2 R H O Me O L H R H 1 H R1 H H V O L O O Me H H R R2 L' L' L' L' OH Me Me t-BuOOH Me Me OH O O HO Me Me O OH Me Me Me R2 R1 OH OH R1 R2 Me t-BuOOH t-BuOOH OH Me Me Hex R OH OH Me Me C5H11 OH Et Me O OH Et Me O O Me Et OH OH Et Me Me OH t-BuOOH t-BuOOH R1 Me Me R1 Me C6H13 C6H13 Me OH R1 R2 O O R2 R1 OH Me O Me Me OH C5H11 Me Me OH O OH Me O OH R Hex O Me Me i-Pr Me C5H11 Me O R2 R1 OH OH R1 R2 O Me OH Me Me O C5H11 Epoxidation of Homoallylic Alcohols with TBHP, VO(acac)2 1.4 : 1 R = (CH2 )7CO2Me 4.6 : 1 Substrate Product Selectivity 2 : 1 Syn diastereomer Anti diastereomer Anti diastereomer Syn diastereomer Anti should be more diastereoselective than syn Homoallylic Alcohols (Mihelich, JACS 1981, 103, 7690) Prediction Control Elements Directed Rxn Diastereoselection 12 : 1 VO(acac)2 + Directed Rxn A(1,3) Strain Control Elements + VO(acac)2 90 % Diastereoselection > 400 : 1 R2 Ratio 104 : 1 > 400 : 1 Yield 92 % 97 % VO(acac)2 + + VO(acac)2 70 % 73 % Yield 85 : 1 70 : 1 R Ratio 2 81 % 16 :1 VO(acac)2 + E. D. Mihelich & Coworkers Diastereoselection = 211 : 1 J. Am. Chem. Soc. 1981, 103, 7690. D. A. Evans Epoxidation of Acyclic Homoallylic Alcohols Chem 206 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
D. A. Evans Epoxidation of Acyclic Homoallylic Alcohols Chem 206 Bishomoallylic Alcohols(Kishi, Tet. Lett. 1978, 19, 2741) Epoxidation Cyclization of Bishomoallylic Alcohols BuOOH, vO(acac) CsHs, RT diastereoselection -9:1 The Kishi Lasalocid Synthesis (JACS 1978, 100, 2933) CO2H 0=R Me' t-BuOoH, vO(acac) ArO CHMe iastereoselection 8- 1 ACOH Evans X-206 Synthesis JACS 1988, 110, 2506 O-R t-BuOOH, vO(acac CHMe? 人人入 e h6, RT R diastereoselection 20.1 (89%)
HO O CO2H Me Me Me OH O Et O Me Et Me Et H H OH A Epoxidation & Cyclization of Bishomoallylic Alcohols A H Et Me Et Me OH Ar O B Me CHMe2 Et OH OH Et Me CHMe2 Me Me Me CHMe2 Et OH Me Me H O V H R Et O O R H Me H O V H R Et O O R O R V O Et O R Me H Me H OH Et Me CHMe2 O O R Me Et OH Me O Me CHMe2 Et OH Me Me OH Et Me CHMe2 O Me OH Et R Me O OH Et R Me O iPr R Et OH Me A Et Ar Me OH Et Me N Et O OBn OH O Me Me Ph O B TBHP AcOH O O O O OH Me Me Me OH Me Me O Me OH OH OH O O Et OH Me H OH Me Me H Me O OH Me R Et iPr C TBHP D AcOH HOAc XN O Et O OBn OH Me Me OH OBn O XN Et O D F Et OH Me iPr O R Bishomoallylic Alcohols (Kishi, Tet. Lett. 1978, 19, 2741) D. A. Evans Epoxidation of Acyclic Homoallylic Alcohols Chem 206 C6H6, RT t-BuOOH, VO(acac)2 diastereoselection ~ 9 : 1 C6H6 , RT t-BuOOH, VO(acac)2 diastereoselection ~ 20 : 1 C6H6, RT t-BuOOH, VO(acac)2 diastereoselection ~ 6 : 1 2nd stereocenter is reinforcing Diastereoselection 8:1 VO(acac)2 Ar = p-MeOPh VO(acac)2 The Kishi Lasalocid Synthesis (JACS 1978, 100, 2933) E Evans X-206 Synthesis JACS 1988, 110, 2506. C6H6, RT diastereoselection 20 : 1 (89 %) VO(acac)2 ● ● ● ● ● ● ● ● ● ● ● ● ● ●
D A. Evans Diastereoselective Hydrogenation: Introduction Chem 206 The Hydrogenation Reaction Polar functional groups may play a role in controlling the diastereoselectivity Relevant Review articles: J M. Brown, Angew. Chem. Int. Edit. 26, 190-203 (1987) however the control elements were not well-defined ■ Genera| Mechanism H2, Pd-C howeve Historically, primary stereochemical control designed around analysis of steric environment in vicinity of C=C However, the influence of polar effects was documented J. E. McMurry& Co-workers, Tetrahedron Lett. 3731 (1970) EtOH 10% Pd-c Pd EtOH Directed OMe Thompson, J.Org. Chem. 36, 2577(1971) 5:95 Y. Kishi& Co-workers, J. Am. Chem. Soc. 102, 7156 (1980)
OMe O O CO2Et CH2OH O O OMe LiAlH4 C C H R H R C C H R H R H H EtOH H2 Pd-C EtOH H2 Pd-C C C H R H R M C C H R H R H M H CO2Et O O OMe H H OMe O O CH2OH C C H R H R C C H R H R M M H H H H N O HO H H H OH CH3 CHMe2 CHMe2 O CH3 H2 H2 H H N OH HO H H H H HO N OH H H CHMe2 H OH CH3 O CH3 CHMe2 Historically, primary stereochemical control designed around analysis of steric environment in vicinity of C=C. However, the influence of polar effects was documented only isomer H2 , Pd-C however trans:cis = 55:45 H2 , Pd-C J. E. McMurry & Co-workers, Tetrahedron Lett.. 3731 (1970) D. A. Evans Diastereoselective Hydrogenation: Introduction Chem 206 The Hydrogenation Reaction Relevant Review articles: J. M. Brown, Angew. Chem. Int. Edit. 26, 190-203 (1987). trans : cis Thompson, J.Org. Chem. 36, 2577 (1971) 5 : 95 trans : cis 85 : 15 Y. Kishi & Co-workers, J. Am. Chem. Soc. 102, 7156 (1980) 10% Pd-C 5% Pd-Al2O3 sole product 12 : 1 Steric Control Directed ? Polar functional groups may play a role in controlling the diastereoselectivity of the hydrogenation process; however, the control elements were not well-defined. + ■ General Mechanism M(0) M(0) + Pd(0) Pd(II)