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