D.A. Evans Olefin Addition Reactions: Part-1 Chem 206 Other Reading material http://www.courses.fasharvard.edu/-chem206/ Smith, K and A. Pelter(1991). Hydroboration of C=C and Alkynes Comprehensive Organic Synthesis. B M. Trost and I. Fleming Chemistry 206 Oxford, Pergamon Press. 8: 703 Advanced Organic Chemistry Beletskaya, I and A Pelter(1997). " Hydroborations catalysed by transition metal complexes. Tetrahedron 53(14): 4957-5026 Brown, H C and P K Jadhav(1983). Asymmetric Hydroboration Lecture number 8 Asymmetric Synthesis. J D. Morrison. New York, AP 2: 1 Olefin Addition reactions-1 Problems of the Day: (To be discussed) Hy Rationalize the stereochemical outcome of this reaction Epoxidation&Directed Epoxidation 9-BBN OH OH diastereoselection 24: 1 Reading Assignment for week Carey& Sundberg: Part B; Chapter 4 W.C. Still &J C. Barrish. J. Am. chem. Soc. 1983. 105. 2487. philic Additions to C-C Multilple Bonds K. Houk. Tetrahedron. 1984. 40. 2257-2274 Theoretical Studies of Stereoselective Hydroboration Reactions Predict the stereochemical outcome of this reaction (Handout) Hoveyda, A H, D A. Evans, et al. Chem. Rev. 1993, 93: 1307-70 NHCONHPh " Substrate-directable chemical reactions"(handout) cHzC20°C % Diastereoselection= 95:5 riaa Matthew d shair October 4. 2002 Roush, J. Org. Chem. 1987, 52, 512
http://www.courses.fas.harvard.edu/~chem206/ Me2CH Me OH Me Ph NHCONHPh 9-BBN OH Me Me2CH OH O NHCONHPh Ph Me D. A. Evans Chem 206 Matthew D. Shair Friday, October 4, 2002 ■ Reading Assignment for week A. Carey & Sundberg: Part B; Chapter 4 "Electrophilic Additions to C–C Multilple Bonds" Olefin Addition Reactions: Part–1 Chemistry 206 Advanced Organic Chemistry Lecture Number 8 Olefin Addition Reactions–1 ■ Problems of the Day: (To be discussed) ■ Hydroboration ■ Epoxidation & Directed Epoxidation ■ Other Reading Material Smith, K. and A. Pelter (1991). Hydroboration of C=C and Alkynes. Comprehensive Organic Synthesis. B. M. Trost and I. Fleming. Oxford, Pergamon Press. 8: 703. Beletskaya, I. and A. Pelter (1997). “Hydroborations catalysed by transition metal complexes.” Tetrahedron 53(14): 4957-5026. Brown, H. C. and P. K. Jadhav (1983). Asymmetric Hydroboration. Asymmetric Synthesis. J. D. Morrison. New York, AP. 2: 1. Hoveyda, A. H., D. A. Evans, et al. Chem. Rev. 1993,93: 1307-70 “Substrate-directable chemical reactions” (handout) W. C. Still & J. C. Barrish, J. Am. Chem. Soc. 1983, 105, 2487. H2O2 diastereoselection 24:1 Rationalize the stereochemical outcome of this reaction Roush, J. Org. Chem. 1987, 52, 5127. m-CPBA CH2Cl2, 0 °C 75 % Diastereoselection = 95 : 5 Predict the stereochemical outcome of this reaction K. Houk, Tetrahedron. 1984, 40, 2257-2274 Theoretical Studies of Stereoselective Hydroboration Reactions (Handout)
D.A. Evans Olefin Addition Reactions: Introduction Chem 206 Representative Cis-Addition Processes Representative Trans-Addition Processes ■ Halogenation M H R C Br-Br M=B.ALetc ■ Hydrogenation i-catalyst H H Oxy-metallation (M= Hg(I), TI(Il) R-C-C-R R-CsC_R R hg(or)2 Group Transfer(epoxidation) RO2H a Oxy-sulfenation (M= s(), Se(l) -ROH Group Transfer(dihydroxylation) R R-S-X—R Attributes Each process may proceed via an bridge a Group Transfer(cyclopropanation intermediate where X is the initiating electro R2 R-C-C、R M-catalyst R2 Olefin substitution may disrupt bridging a Addition of hydrogen halides Cycloadditions(one of many ! R2C=C=0一R R H H H-C-C Attributes Attributes: Each process adds to the C=C via a stereospecific process Process may proceed via an bridged intermediate where H+ is the initiating electrophile Intermediates may be involved in some of the indicated reactions R→C-C-R Olefin substitution reaction conditions as well as halide type may disrupt bridging
C C H R H R C C H R H R M H H H C C H R H R –ROH C C H R H R –N2 C C H R H R –N2 OsO4 C C H R H R –N2 RO2H R2C=N2 R2C=C=O C C H R H R M H C C H R H R O O Os O O C C H R H R H H C C H R H R O C C H R H R R O R C C H R H R R2 C C C H R H R C C H R H R C C H R H R C C H R H R H–X Hg(OR)2 R–S–X Br Br C C H R H H R X C C H R H RO R S–R C C H R H Br R Br C C H R H RO R Hg–OR C C H R H R X C C H R H R H C C R H H H R X D. A. Evans Olefin Addition Reactions: Introduction Chem 206 Representative Cis-Addition Processes ■ Hydrometallation + M = B, Al, etc + ■ Hydrogenation M-catalyst + ■ Group Transfer (epoxidation) + ■ Group Transfer (dihydroxylation) + ■ Group Transfer (cyclopropanation) M-catalyst Attributes: Each process adds to the C=C via a stereospecific process Intermediates may be involved in some of the indicated reactions + ■ Cycloadditions (one of many!) Representative Trans-Addition Processes ■ Halogenation + ■ Oxy–metallation (M = Hg(II), Tl(III) + ■ Oxy–sulfenation (M = S(II), Se(II) + Attributes: Process may proceed via an bridged intermediate where H+ is the initiating electrophile Olefin substitution, reaction conditions as well as halide type may disrupt bridging ■ Addition of hydrogen halides + + Attributes: Each process may proceed via an bridged intermediate where X is the initiating electrophile Olefin substitution may disrupt bridging
D. A. Evans Allylic Strain Olefin Hydroboration Chem 206 ■ The basic process Hydroborations dominated by A(1, 3)Strain CHOBn CH2OBn H2B OM OMe a Response to steric effects: Here is a good calibration system diastereoselection 12. 1 Oxidant Ratio, A: E Reference Y Kishi& Co-workers. J Am. chem. Soc. 1979. 101. 259 MCPBA 6931OC,1967,32,1363 BH3, H202 34660c1970,35,2654 Bno a Acyclic hydroboration can be controlled by A(1, 3)interactions Diastereoselection =3.1 OH major diastereomer C.H. Heathcock et al. tetrahedron lett 1984 25 243 H2O2 control elements A(1, 3)allylic strain Steric effects; RL vS RM Thexy BH2 Staggered transition states major CHoR CHoR then BH3 TrO Tro Diastereoselection: 4: 1 Houk, "Theoretical Studies of Stereoselective Hydroboration Reactions etrahedron 1984, 40, 2257(Handout W.C.: Barrish. J C. J. Am. Chem. Soc. 1983. 105 2487
Me3C H CH2 A B H H H S C C R R R R RL OH RM Me B2H6 MCPBA RL RM H H C C Me CH2OR B H H H H2O2 C R R C R R B S H H H RL RM RM Me OH RL OH H H C C Me CH2OR B H H H C H C H2B R R R R Me OH OMe O Me Me TrO OTr Me OH Me O CH2OBn Me Me OH Me OH Me OH Me TrO OTr Me BnO OH Me Me Me B2H6 B2H6 B2H6 Me Me CH2OBn O OH OH TrO OTr Me OH Me OH Me Me O OMe Me OH OH OH Me Me Me BnO OH OH Me TrO OH Me OH Me OH Me OH OTr Still, W.C.; Barrish, J. C. J. Am. Chem. Soc. 1983, 105, 2487. Diastereoselection; 4: 1 ThexylBH2, then BH3 ThexylBH2, then BH3 Diastereoselection; 5 : 1 H2O2 Diastereoselection = 3:1 C. H. Heathcock et. al. Tetrahedron Lett 1984 25 243. H2O2 diastereoselection 12:1 Y. Kishi & Co-workers, J. Am. Chem. Soc. 1979, 101, 259. diastereoselection 8:1 H2O2 Hydroborations dominated by A(1,3) Strain Staggered transition states Steric effects; RL vs RM A(1,3) allylic strain control elements Houk, "Theoretical Studies of Stereoselective Hydroboration Reactions" Tetrahedron 1984, 40, 2257 (Handout) major diastereomer ■ Acyclic hydroboration can be controlled by A(1,3) interactions: BH3, H2O2 34:66 JOC, 1970, 35, 2654 69:31 JOC, 1967, 32, 1363 Oxidant Ratio, A:E Reference E ■ Response to steric effects: Here is a good calibration system: ‡ ■ The basic process D. A. Evans Allylic Strain & Olefin Hydroboration Chem 206 d+ d– major minor
D A. Evans Allylic Strain Olefin Hydroboration Chem 206 What about the following substitution pattern? a Case l: Dialkylboranes H2o, R2BH structure is a potential vanable favored for R2BH Me RL M H Houk's rules: Orient RL anti-periplanar to incoming reagents to avoid TS eclipsing minor ■ Case I: Borane Midland finds that TSy favored for R2BH reagents, but TS1-TS2 for BH3 thers have found that TS, favored over TS for BH3 Representative Examples H L H202 from Lecture 4: The Torsional Energy Profile eMe M. M. Midland Co-workers J.Am. Chem. soc.1983,105,3725 thexylborane 14 n R=CHMe2: diastereoselection 24: 1 H ①=110 1.39 kcal Model is consistent if you presume HO RM R=RL +0.06 kcal W.C. still j c Barrish, Am chem. Soc. 1983. 105 2487
H H H H H H H H H H RL RL Me H C C Me H C H C Me H Me H C H C Me Me C H C Me Me H B H H H C C H H Me B H H C C Me H H H RM H R B C H C H H Me R H Me C C H H H B R R OH Me R OH R Me OH 9-BBN R2BH RL H2O2 H Me H H CH2OH Me H Me CH2 H H Me RM Me TS1 RL OH 9-BBN RM BH3 A RL H2O2 RL OH Me RM TS2 BH3 B RM H2O2 RM Me TS2 RL OH R2BH H2O2 RL OH Me RM R2BH RL Me RM H2O2 RL OH Me RM H2O2 RM Me RL OH TS1 RM R2BH R2BH R2BH structure is a potential variable D. A. Evans Allylic Strain & Olefin Hydroboration Chem 206 What about the following substitution pattern? Houk's rules: Orient RL anti-periplanar to incoming reagents to avoid TS eclipsing: favored for BH3 from Lecture 4: ■ Case I: Borane +2.68 kcal +1.39 kcal +0.06 kcal F = 180 F = 110 F = 50 F = 0 F = 0 F = 180 The Torsional Energy Profile Midland finds that TS1 favored for R2BH reagents, but TS1 ~ TS2 for BH3 Others have found that TS1 favored over TS2 for BH3 favored for R2BH ■ Case II: Dialkylboranes Representative Examples 1 : 1 4 : 1 14 : 1 26 : 1 diastereoselection borane methylsulfide thexylborane 9-BBN dicyclohexylborane M. M. Midland & Co-workers, J. Am. Chem. Soc. 1983, 105, 3725.. H2O2 W. C. Still & J. C. Barrish, J. Am. Chem. Soc. 1983, 105, 2487. R = CHMe2 : diastereoselection 24:1 R = n-Bu: diastereoselection 11:1 H2O2 Model is consistent if you presume HO = RM: R = RL major minor major minor
D. A. Evans Allylic Strain& Olefin Hydroboration Chem 206 Case I: Dialkylboranes ■ Case I: Borane Ru favored for R2BH minor R2BH minor favored for BH3 Evans, Ratz, Huff, Sheppard, JACS 1995, 117, 3448-3467 H Me H e Lonomycin A Me OH c-9→C10 TS, favored TS2ds台 avored diastereoselection 9-BBN TA, disfavored TA2 favored 60% diastereoselection
RM RO RO RM RM RM RO RO O Me Me OMe Me OMe Me O H OH Me O N O Bn A Lonomycin A RL Me C C H H H B R R R B C H C H H Me R B H RL H C H O HO2C O Me OMe Me Me OMe Me OH Me O O Me Me O O Me OMe Me OMe Me Me OH H H D F C B C H Me H H H H C B C H Me H H R R RL RL H H RL B H H H C C H H Me B H H C C Me H H H H RL H RL RL C H C B H Me H H H C H C B H Me H R R H H E 9 TS2 TS1 H2O2 R2BH H2O2 R2BH BH3 •SMe2 9-BBN RM Me RL OH RL OH Me RM XP O Me Me OMe Me OMe Me O H OH Me OH OH XP O Me Me OMe Me OMe Me O H OH Me TS2 TS1 A B BH3 BH3 H2O2 H2O2 RL OH Me RM RM Me RL OH D. A. Evans Allylic Strain & Olefin Hydroboration Chem 206 favored for BH3 favored for R2BH ■ Case I: Dialkylboranes ■ Case II: Borane TS1 favored TS2 disfavored 1 5 9 9 5 1 1 5 10 diastereoselection > 95 : 5 diastereoselection 92 : 8 85% 60% TA1 disfavored TA2 favored Evans, Ratz, Huff, Sheppard, JACS 1995, 117, 3448-3467. C-9 ® C10 10 10 9 major major minor minor
D.A. Evans Represetative Hydroboration EXamples: Acyclic Control Chem 206 For each of the examples shown below, attempt to rationalize the CO2H 1.9-BBN stereochemical outcome of the reaction in terms of one of the models presented in the discussion CH2 2. H,02, NaOH Me Wolinsky, J; Eustace, E.J. J. Org. Chem1972,37,3376 Diastereoselection =7: 1 Me 1.9-BBN 2. H202, NaOH Y Kishi& Co-workers, J. Am. Chem. Soc. 1978. 100. 2933 ° one isomer Me Me J∴ Nelson.D Tetrahedron. 1968. 25. 3767 Diastereoselection 10: 1 Me BH?THF B2H6/[o] M Mon. K Tetrahedron 1976. 32 diastereoselection 12. 1 Diastereoselection 19: 1 人 CH H3 Diastereoselection 32.1 Me R=H etrahedmn Lett. 1983. 19. 1987 R=oBn Diastereoselection 6.6: 1 BH3THF Diastereoselection 10: 1 B2H6/[o] Birtwistle et. al R=CH3: Diastereoselction=6.7: 1 ett1986,25,243. R=isopropyl "One Compound Schulte-Ette K.H. Orloff. G OH He/y. Chim. Acta 1967. 50. 153 Diastereoselection = 4.6
CO2H CH2 Me Me Me OH CH2 Me Me Me CH2 CO2H Me OH CH2 Me Me OH CH2 Me Me OH CH2 Me O O Me Et OH Et H Me Et Et Et Et Me Et OH R O O O Me Me Me Me Me O Me O HO O OBn O O CH3 CH3 R H CH3 CH3 O O OBn HO O R H R OH R OH OH H B2H6 BH3 .THF BH3 .THF BH3 .THF O Me O Me H H H Me Me O O Me OH Me H OH OH H Me OH Me Me OH Me H OH OH H Me OH Me D. A. Evans Represetative Hydroboration Examples: Acyclic Control Chem 206 Y. Kishi & Co-workers, J. Am. Chem. Soc. 1978, 100, 2933. "one isomer" H2O2 diastereoselection 12:1 Mori, K. Tetrahedron 1976, 32, 1979 R=H; Diastereoselection = 6.8:1 R=OBn Diastereoselection = 6.6:1 Oikawa et. al. Tetrahedron Lett. 1983, 19, 1987. R = CH3; Diastereoselction = 6.7:1 R = isopropyl "One Compound" Birtwistle et. al. Tetrahedron Lett. 1986, 25, 243. B2H6/[O] B2H6/[O] B2H6/[O] Schulte-Ette, K.H.; Ohloff, G. Helv. Chim. Acta 1967, 50, 153. Diastereoselection = 4.6:1 Diastereoselection = 10:1 Diastereoselection = 32:1 Diastereoselection = 19:1 B2H6/[O] 1. 9-BBN 2. H2O2, NaOH Diastereoselection = 10:1 Wolinsky, J.; Nelson, D. Tetrahedron. 1968, 25, 3767. Wolinsky, J.; Eustace, E. J. J. Org. Chem. 1972, 37, 3376. Diastereoselection = 7:1 1. 9-BBN 2. H2O2, NaOH For each of the examples shown below, attempt to rationalize the stereochemical outcome of the reaction in terms of one of the models presented in the discussion
D. A. Evans Representative Hydroboration EXamples: Cyclic Systems Chem 206 CH2 BH3 THF Diastereoselection= 2.1: 1 B Fraser-Reid et al J.Am.Chem.Soc.1984,106,73 isomer, no ratio given BH3 THF H3 Diastereoselection 1.2: 1 BH3THF CH2 BH3THF 90% yield, chem.Soc.1967,89,6762. no diastereoselection given Diastereoselection =3.3: 1 BH3THF CH2 BH3THF COmE Ley, S. et al 55% yield with the diastereomeric J. Chem. Soc. Chem. Commun. 1983630. alcohol produced in an unspecified Diastereoselection= 24: 1 amount. Recycling of the minor isomer furtherprovided 15% of the desired material BH3THF N-NHAr N-NHAr Diastereoselection 4.9: 1 Y Senda et al Compare with H.C. Brown's Tetrahedron 1977. 33. 2933 case,with 9-BBN: 1.5: 1) McMurry, J.E. Minor diastereomer not detected JAm.chem.Soc.1968,90,6321
Me3C CH2 BH3 .THF CH2 Me3C Me Me CH2 Me3C Me Me3C CH2 Me Me CH2 BH3 .THF BH3 .THF BH3 .THF BH3 .THF OH Me Me Me3C OH Me3C Me Me3C OH OH Me3C Me OH Me Me OH BnO HO O H H O N–NHAr Me Me Me H H N O O O CH2 H H CH3 O CH2 Me CO2Me H Me BH3 .THF BH3 .THF BH3 .THF BH3 .THF H Me Me Me N–NHAr OH O O H H HO BnO OH Me OH Me H CO2Me Me O OH H CH3 H H O O O H N OH D. A. Evans Representative Hydroboration Examples: Cyclic Systems Chem 206 Diastereoselection = 2.1:1 Diastereoselection = 3.3:1 Diastereoselection = 2.4:1 Diastereoselection = 4.9:1 (Compare with H.C. Brown's case, with 9-BBN; 1.5:1) Y. Senda et. al. Tetrahedron 1977, 33, 2933. Diastereoselection = 1.2:1 Minor diastereomer not detected McMurry, J. E. J. Am. Chem. Soc. 1968, 90, 6321. Ley, S. et.al. J. Chem. Soc. Chem. Commun. 1983 630. Major isomer; no ratio given. B. Fraser-Reid et. al. J. Am. Chem. Soc. 1984, 106, 731. 90% yield, no diastereoselection given Sallay, S. I. J. Am. Chem. Soc. 1967, 89, 6762. 55% yield with the diastereomeric alcohol produced in an unspecified amount. Recycling of the minor isomer furtherprovided 15% of the desired material
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 Claisen Rearranger via re A-r favored favored product CHaI Nonbonding Interactions disfavor the syn diastereoface Simmons-Smith Reaction Directed Reactions Hydroxyl-directed Reactions Review. Hoveyda, Evans, Fu Chem. Reviews 1993, 93, 1307 MCPBA ratio 92 a Associative Substrate-Reagent Interactions J. Chem.Soc.1958,(1957) A-B - A-B A-B vo(acac)2 atio 98:2 JAcS95,6136,(1973) disfavored Noncovalent interaction favors the syn diastereoface A-B Eta ( CH2 Directed Oxidations Win oxidation As91,6892, hydroboration ratio 90: 10 Agenda Directed Reductions Hydride reduction JAcS105.1072(1983) Directed c-c Bond constructions JACS106,3866(1984
X R A B A B X A B R B A X B A A B C C H H H A B C C H H H A B A B OH OH R R OH Et2Zn MCPBA Cl CO3H t-BuOOH Et2Zn CH2I2 OH Me CH2 I2 R O CH2 R O Zn CH2 I R 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 Peracid Ep Orientation of the Directing Group A Rao in Comprehensive Organic Synthesis, Trost, Ed, 1992, Vol 7, Chapter 3.1 ■ General reaction: X=O, CH2 LUMO TC-C g0-0 0-0 bond energy: -35 kcal/mol The transition state 米 Orientation of directing group is not the same for all reactons View from below olefin Selectivity a Reaction rates are governed by olefin nucleophilicity. The rates of t-BuO2H, V+5 50 epoxidation of the indicated olefin relative to cyclohexene are provided RCO3H 95:5 CH22, Zn-Cu ? The transition state bite angles for the above reactions are either a The indicated olefin in each of the diolefinic substrates may be oxidized not known or have been only crudely estimated selectively The best guesses
OH R O O O R R R 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 OAc OH H Me Me Me Me 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 ■ The transition state: View from below olefin O-O bond energy: ~35 kcal/mol A. Rao in Comprehensive Organic Synthesis, Trost, Ed., 1992, Vol 7, Chapter 3.1
D. A. Evans Diastereoselective Peracid Epoxidation Chem 206 Stereoelectronic Implications of intramolecular Peracid Epoxidation The Directed Peracid Epoxidatic 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 CF3 R-0 require more acidic peracid both allylic alcohols and ethers OK OTBS(m-CPBA)(CF3CO3H) 50:1 5:1 24:1 00:1 12:1 100:1 1:6 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 ● ● ● ●