哈佛大学：《高等有机化学》（英文版）Lecture 10 A Diastereoselective Attack of Electrophiles on Chiral Olefins

Chemistry 206 Advanced Organic Chemistry Handout-10A Diastereoselective Attack of Electrophiles on Chiral olefins Michael dart Evans Group Seminar, January 18, 1994 Matthew d. shair Wednesday October 9. 2002

Chemistry 206 Advanced Organic Chemistry Handout–10A Diastereoselective Attack of Electrophiles on Chiral Olefins Matthew D. Shair Wednesday, October 9, 2002 Michael Dart Evans Group Seminar, January 18, 1994

Mick dart Diastereoselective Attack of Electrophiles on Chiral Olefins Diastereoselective Die/s-Alder reactions: Chiral Dienes Diastereoselective Attack of Electrophiles on chiral olefins D. Jones. J C. S. Chem. Comm. 1980. 739 Hehre's Proposal Based solely on electrostatic considerations 1. Diels Alder reactions 2. Halogenation and related electrophilic additions Electron rich 3. Reactions of allylsilanes Electron Poor Anti 4. Hydroborations 5. Osmylations Electron Rich Substituents have lone pairs(OR, Nr2, SR, SO2R) Electron Poor Substituents: SiR3(electropositive) Kahn Hehre J. Am. Chem. Soc. 1987. 109. 663-666 Mick dart Evans Group Seminar Tues, Jan. 18. 1994 I StereocontroL: A(1, 3)strain Diastereoselection 91:9 % ■ Opposite diastereofacial selectivity is observed with acrolein Trost,Jorg.chem,1989.54,2271-2274 A-01-Diels-Alder 10/9/00 12: 12 AM

Electron Rich Substituents have lone pairs (OR, NR2, SR, SO2R) Electron Poor Substituents: SiR3 (electropositive) Based solely on electrostatic considerations Mick Dart Evans Group Seminar Tues. Jan. 18, 1994 1. Diels Alder reactions 2. Halogenation and related electrophilic additions 3. Reactions of allylsilanes 4. Hydroborations 5. Osmylations Diastereoselective Attack of Electrophiles on Chiral Olefins D. Jones, J. C. S. Chem. Comm. 1980, 739. ■ Other dienophiles also give adducts derived from endo addition syn to the hydroxyl anti syn X Dienophile Syn Anti Electron Rich Electron Poor Hehre's Proposal: ■ Opposite diastereofacial selectivity is observed with acrolein. (73%) ■ Stereocontrol: A(1,3) strain Trost, J. Org. Chem, 1989, 54, 2271-2274. Diastereoselective Diels–Alder Reactions: Chiral Dienes Diastereoselection 91 : 9 Diastereoselection >95 : 5 Kahn & Hehre, J. Am. Chem. Soc. 1987, 109, 663-666. (99%) PhN O O O O Me H H O NPh Me OH H H OH O H H Me H O H R X H Me Me OH O O O O O O Me Me H OH H OH Me Mick Dart Diastereoselective Attack of Electrophiles on Chiral Olefins 10A-01-Diels-Alder 10/9/00 12:12 AM

Diastereoselective Die/s-Alder Reactions. Chiral Dienes co Me le,100℃c SiMe2Ph SiMegPh Fleming, JCS Perkin Trans L, 1989, 2023-2030. L Diastereoselection 82: 18 Fleming JCS Perkin Trans 1, 1989, 2023-2030 10 days OMe PhMe,100℃ OSiEr COmE R Franck, J Am. Chem. Soc. 1988, 110, 3257 Diastereoselection 12: 88 OSiMe3 R Franck, J. Am. Chem. Soc. 1988, 110, 3257 Diastereoselection 27: 73 a Rationalization for diastereofacial selectivity Allylsilane Dienophile Dienophile inside SiMe= Ph Allylic Ether Dienophile OSiMe3 ee Houk Co-workers Science. 1986. 221. 1108-1117 10A-02-Diels-Alder 10/8/00 8: 11 PM Also see A Kozikowski. J. Am. Chem. Soc. 1987. 109. 5167-5175

Also see A. Kozikowski, J. Am. Chem. Soc. 1987, 109, 5167-5175. Allylic Ether Allylsilane Favored diene conformers in reactions with acetylenic dienophiles Dienophile ■ Rationalization for diastereofacial selectivity: Fleming, JCS Perkin Trans I, 1989, 2023-2030. Diastereoselective Diels–Alder Reactions: Chiral Dienes Diastereoselection 82 : 18 Diastereoselection 12 : 88 R. Franck, J. Am. Chem. Soc. 1988, 110, 3257 Dienophile Dienophile Dienophile Dienophile PhH, rt PhH, 60 °C 10 days 2 days (96%) (90%) 2 days PhMe, 100 °C Dienophile Dienophile Dienophile R. Franck, J. Am. Chem. Soc. 1988, 110, 3257 Diastereoselection 27 : 73 Diastereoselection >99 : 1 Fleming, JCS Perkin Trans I, 1989, 2023-2030. PhMe, 100 °C 2 days (72%) (62%) See Houk & Co-workers Science, 1986, 221, 1108-1117. anti outside inside Dienophile Me H SiMe2Ph Me PhN O O NPh O O H SiMe2Ph Me Me H H H NPh O O H OSiMe3 Me Me H H H H H H Me Me OSiMe3 H O O NPh SiMe2Ph Me H H H Me Me Me SiMe2Ph H O O NPh O O PhN Me OSiMe3 H Me H Me H Me OSiMe2 Me Me3SiO H Me Me Me H H OSiMe3 Me PhMe2Si Me Me Me3SiO H Me Me H OSiMe3 Me Me H OSiMe3 Me CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me H SiMe2Ph Me Me Me H H Me SiMe2Ph CO2Me CO2Me CO2Me CO2Me Me H OSiMe3 Me Me H H H Me Me Me OSiMe3 H SiMe2Ph H Me Me SiMe2Ph H Me CO2Me CO2Me CO2Me CO2Me H SiMe2Ph H Me SiMe2Ph H Me Me PhMe2Si Me 10A-02-Diels-Alder 10/8/00 8:11 PM

iodolactonization R=H trans Kinetic NIS,cHCl325°C 75:25 Gauche B is more destabilizing than gauche A Thermodynamic 3 equiv h, MeCN, O"C Bartlett, J Am. Chem. Soc. 1978. 100, 3950-3952 a iodolactonization of allylic alcohols Substrate A(1, 2 )strain Me Meo Ratio =3:97 R=H87:1341 R=H77:2374 Gauche a is now more R=Me42:5881 stabilizing than gauche B A preference for "inside alkoxy is observed in these cydlizat Rato>95:5(49% Chamberlin. J. Am. Chem. Soc. 1983. 105. 5819-5825 ynamic conditions"produced complex mixtures roxy group(TBS or Ac)does not affect selectivity Chamberlin, J. Am. Chem. Soc. 1983, 105, 5819-5825.1 How can the above results be rationalized 10A-03-lodolactonization 10/8/00 8: 11 PM

A preference for "inside alkoxy" is observed in these cyclizations A B low yield due to δ-lactone formation Gauche A is now more destabilizing than gauche B + I2, HOH/THF HCO3 – Ratio >95 : 5 (49%) A + B How can the above results be rationalized? Chamberlin, J. Am. Chem. Soc. 1983, 105, 5819-5825. K2CO3 MeOH Epoxidation Ratio = 3 : 97 Lactonization Ratio = 96 : 4 t-BuOOH VO(acac)2 Gauche B is more destabilizing than gauche A + Ratio 96 : 4 (85%) HCO3 – I2, HOH/THF + R = H R = Me A(1,2) strain 95 : 5 49 ■ Kinetic conditions: 3 equiv I2, aq Na2CO3, Et2O, 0 °C ■ Protection of the hydroxyl group (TBS or Ac) does not affect selectivity ■ Iodolactonization of allylic alcohols 75 : 25 9 : 91 (cis : trans) NIS, CHCl3, 25 °C 3 equiv I2, MeCN, O °C Kinetic Thermodynamic Conditions Bartlett, J. Am. Chem. Soc. 1978, 100, 3950-3952. Iodolactonization Substrate Major Product Selectivity Yield (%) 85 74 81 41 94 66 R = H R = Me 95 : 5 87 : 13 90 : 10 93 : 7 77 : 23 42 : 58 R = H R = Me Chamberlin, J. Am. Chem. Soc. 1983, 105, 5819-5825. ■ Bartlett's "thermodynamic conditions" produced complex mixtures I HO O O O O HO I Me Me R R Me OH HO O -O2C CH2 HO H O C H C HMe HO I Me O H HO O I I O HO H O C I H OH C Me H R R Me H HO CH2 Me OH Me -O2C O RO OH Me HO O O HO OH OH HO O O I Me O Me I O Me HO O O O O Me OH Me RO O -O2C CH2 HO Me Me HO H C Me C H Me I O Me HO O I I O HO Me O Me HO C I C Me H Me H CH2 -O2C O MeO Me OH Me Me I H I HO O O O Me OH Me MeO O O O OH O I Me 10A-03-Iodolactonization 10/8/00 8:11 PM

Mode/ for Stereoinduction? lodo diol formation from allylic alcohols minor I Analysis: D. A Evans, Chem. 115, Lecture 23, Dec. 16, 1993 Ho Me l2, AgOAC ■ Prevost conditions:2 equiv k2,2 equiv AgOAC, THF,-78-40°℃ a Other conditions: I2, THF/phosphate buffer; I2, THF, aq Na2CO3 provide 1, 3-diols in very high selectivi also observed with allylic ethers(OMe, OBn, OTBS Chamberlin, Tetrahedron 1984, 40, 2297-2302 Gauche A is now more Cytovaricin Synthesis tio80:20 Diastereoselection 96: 4 I Place the medium size group(-OH)outside and the small group (-H) inside Evans. Kaldor. Jones. J. Am. Chem. Soc. 1990. 112. 7001 2, HOH/THF 10A-04-lododiol formation 10/8/00 8: 11 PM

■ Place the medium size group (–OH) outside and the small group (–H) inside ■ Other conditions: I2, THF/phosphate buffer; I2, THF, aq Na2CO3 provide 1,3–diols in very high selectivity Model for Stereoinduction? major minor Gauche B is more energetically destabilizing than gauche A I2, AgOAc + + – OAc AcO– B A A B H2O + + I2, AgOAc Gauche A is now more destabilizing than gauche B OH2 Ratio 80 : 20 perfect regioselectivity HCO3– I2, HOH/THF Poor regioselectivity affords a mixture of products Evans, Kaldor, Jones, J. Am. Chem. Soc. 1990, 112, 7001. Chamberlin, Tetrahedron 1984, 40, 2297-2302. Diastereoselection 96 : 4 I2, THF aq KH2PO4 Cytovaricin Synthesis ■ High selectivities are also observed with allylic ethers (OMe, OBn, OTBS) ■ Prevost conditions: 2 equiv I2, 2 equiv AgOAc, THF, –78 →0 °C 94 : 6 98 : 2 95 : 5 80 : 20 78 90 85 Substrate Major Product Selectivity Yield (%) Iodo diol formation from allylic alcohols ■ Analysis: D. A. Evans, Chem. 115, Lecture 23, Dec. 16, 1993 HO H R C H H OAc I OH R R' OH C Me I R' HO H R C Me C HH I I Me OH Me OH Bu Bu Me R Me OH TIPSO Me Bu OH Me OH Me OAc R Bu R' OH I OH OH Bu I Me OAc C C I H OH Me OH Bu OAc OH Me R R HO OH R OH OH Me I OH R Me Me Bu Bu OH I I I I Me HO Me OAc TIPSO OH R' H H R HO C C I HO H H R' R H 10A-04-Iododiol formation 10/8/00 8:11 PM

u Acomplete tumover in olefin diastereofacial selectivity is bserved when adding intemal and extemal nucleophiles Hehre's Analysis 人一 Addition product cis trans 95:5 Nu ti99:1 Favored ground. l2 General observation Disfavored a-complex Favored iodonium ion the major diastereomer from electrophile-induced cyclization is opp observed in the analogous intermolecular electrophilic addition. For a review of eletrophilic induced olefin cyclization reactions see Cardillo M. Orena. Tetrahedron 1990. 46. 3321 Chamberlin& Hehre s Rationalization More reactive ground-sta vred-comp杷ex I"Facial preferences in electrophilic addition reactions are not invariant with respect to the location of the transition state along the reac a Change in diastereoselectivity is a consequence of a change in the rate-limiting step O Addition reactions: Formation of an onium ion intermediate sequently trapped by a Nu from the medium) e Cyclization reactions: Intramolecular attack on a t-complex(not an onium ion) I Analysis of the stereoselectivity of electrophilic addition to chiral olefins 1. Relative abundances of conformational minima 2. Relative reactivities of the available form Houk: Argument for the inside alkoxy effect" in T-complex formation 3. Stereoselectivies of the individual conformers I I-complex cyclizes if R contains a Nu and its formation is rate determining Chamberlin& Hehre, J. Am. Chem. Soc. 1987, 109, 672-677.i Onium ion formation is rate determing in the addition reactions Seminar I The presence or absence of an intemal nucleophile acts to determine the Synthetic and Mechanistic Review of Electrophilic Haloge 1992 ereochemical outcome of the reaction by modifying the nature(timing)of ansition state 10A-05-lodolact/Hehre 10/8/00 8: 12 PM

■ "The presence or absence of an internal nucleophile acts to determine the stereochemical outcome of the reaction by modifying the nature (timing) of transition state. ■ Onium ion formation is rate determing in the addition reactions ■ π–complex cyclizes if R contains a Nu and its formation is rate determining For a review of the halogenation reaction see: Andy Ratz, Evans Group Seminar, Synthetic and Mechanistic Review of Electrophilic Halogenation, May 7, 1992. For a review of elctrophilic induced olefin cyclization reactions see: G. Cardillo & M. Orena, Tetrahedron 1990, 46, 3321. ■ "Facial preferences in electrophilic addition reactions are not invariant with respect to the location of the transition state along the reaction coordinate." Chamberlin & Hehre, J. Am. Chem. Soc. 1987, 109, 672-677. - I2 I2 OH2 cis : trans 95 : 5 ratio 99 : 1 I2 I2 H2O ■ A complete turnover in olefin diastereofacial selectivity is observed when adding internal and external nucleophiles Chamberlin & Hehre's Rationalization For electrophiles that react via onium intermediates (I2, Br2, Hg(OAc)2, PhSeCl), the major diastereomer from electrophile-induced cyclization is opposite to that observed in the analogous intermolecular electrophilic addition. General Observation: ■ Analysis of the stereoselectivity of electrophilic addition to chiral olefins: 1. Relative abundances of conformational minima 2. Relative reactivities of the available forms 3. Stereoselectivies of the individual conformers ■ Change in diastereoselectivity is a consequence of a change in the rate-limiting step ● Addition reactions: Formation of an onium ion intermediate (subsequently trapped by a Nu from the medium) ● Cyclization reactions: Intramolecular attack on a π–complex (not an onium ion) + + Nu Nu Disfavored π–complex Favored π–complex Disfavored iodonium ion Favored iodonium ion Cyclization product Addition product Favored ground￾state conformer More reactive ground-state conformer Hehre's Analysis Houk: Argument for the "inside alkoxy effect" in π–complex formation O O HO OH Bu Me OH I Me I H I OH Bu Me OH H I Me HO O O Bu H HO OH Bu Me Me OH HO O O O Me OH H I2 H O O H H R H OH Me Me OH H R H I HO Me Me I H OH Bu Me OH I Me H R HO H H H H H H HO R H Me Me H R HO H H H H OH H R Me I I2 10A-05-Iodolact/Hehre 10/8/00 8:12 PM

Diastereoselective Functionalization of (E) Allylic Alcohols Oxymercuration of Acyclic allylic alcohols D. A Evans. Chem 115 Lecture 23 Dec. 16. 1993 ■ Halogenation HoH76:246 Giese. Tet Lett 1985. 26. 1197 Ac ACO Et MeOH 93: 07 72% - Ph HOH88:1266% Gauche b is more enero - tBu Hoh98:0270% major ■ Oxymercuration syn: anti=80: 20 Chamberlin. Tetrahedron 1984. 40. 2297-2302. O-acetate participation will tum over the stereochemical course of the n ■ Sulfenylati oMe HOH Rato=99:1{40%) Favored Reetz, Angew. Chem. Int Ed. 1987, 26, 1028-1029. Ratio=50: 50(77%) ■ Hydroboration Af least 3 major products 10A-06-Oxymercuration 10/8/00 8: 12 PM Hehre's model could be invoked to explain turnover in -facial selectivity

D. A. Evans, Chem. 115, Lecture 23, Dec. 16, 1993 Diastereoselective Functionalization of (E) Allylic Alcohols ■ Halogenation ■ Oxymercuration ■ Hydroboration ■ Sulfenylation At least 3 major products H2O2 ThexylBH2 Ratio = 99 : 1 (40%) PhS–Cl Me2Zn TiCl4 + Ratio = 50 : 50 (77%) Me2Zn TiCl4 PhS–Cl + Reetz, Angew. Chem. Int. Ed. 1987, 26, 1028-1029. minor major Gauche B is more energetically destabilizing than gauche A syn : anti = 80 :20 Chamberlin, Tetrahedron 1984, 40, 2297-2302. Hg(OAc)2 I2, AgOAc + + – OAc AcO– B A Hg(OAc)2 R'OH Oxymercuration of Acyclic allylic alcohols: NaBH4 R R'OH Ratio -Et HOH 76 : 24 yield 65% -Et MeOH 93 : 07 72% -Ph HOH 88 : 12 66% -tBu HOH 98 : 02 70% Giese, Tet. Lett. 1985, 26, 1197 Hg(OAc)2 NaBH4 HOH Hg(OAc)2 syn syn : anti = 77 : 23 O-acetate participation will turn over the stereochemical course of the rxn Iodohydroxylation of these substrates is not regioselective + + + + Disfavored Favored ■ Hehre's model could be invoked to explain turnover in π–facial selectivity O H RL C H C n-Bu OH Me OAc I OH H H Hg X R' O R H C Hg X H H C H RL O R OH OH R R C Hg RL H H C H OR' HgOAc OR' R H Me OH X C Hg H X C H H OH OH H n-Bu R' HO RL OH RL HgOAc HgOAc Me OH OR' n-Bu RL HO OH OH OH RL OR' HgOAc O R OR Me Me RL OR Et OR RL Me OR HO OBz H OH Et Me OBz OBz Et C H C HMe Hg X R R' R OH I OAc C C I H S Ph C H C Et H H MeO Me Me Me SPh Me TBSO Et OMe Me Me OTBS Me TBSO Me SPh Me Me MeO Me SPh Et Me Me OH R' H H R HO C C I HO H H R' R H n-Bu 10A-06-Oxymercuration 10/8/00 8:12 PM

tereochemical Model For Electrophilic Attack on Allylsilanes Electrophilic Attack on Allylsilanes PhMe mCPBA The products on the left r Path a Path B 91 2g If A> Me, then Path a dominates due to a(1, 3)strain I IfA H, then Path B can compete a Larger R groups result in higher selectivity a The size of R is more important in locking the substrate into the ading to Path A than in shielding the E Afynsianes and the sicon g fect Dec 1l, 190 5 425.0 Fleming, JCS Perkin Trans L, 1992, 3303-3308 OA-07-Allylsilanes 1018/00 8: 13 PM

Scott J. Miller Evans Evening Seminar, "The Chemistry of Allylsilanes and the β Silicon Effect," Dec 11, 1990, p 45. Path A Path B Paddon-Row, Rondan, and Houk JACS 1982 104, 7162. + + El+ El+ ■ If A = H, then Path B can compete ■ If A ≥ Me, then Path A dominates due to A(1,3) strain tereochemical Model For Electrophilic Attack on Allylsilanes Model assumes: 1. Electrophilic attack anti to the silyl moiety 2. The silyl group is the "large" substituent Electrophilic Attack on Allylsilanes mCPBA Me iPr PH 61 : 39 >95 : 05 89 : 11 R Ratio R Ratio 58 : 42 >95 : 05 91 : 09 Me iPr PH AlMe3 OsO4 Me iPr PH 34 : 66 67 : 33 92 : 08 R Ratio CH2I2 ■ Epoxidation ■ Cyclopropanation ■ Osmylation The products on the left correspond to attack by Path A ■ Larger R groups result in higher selectivity ■ The size of R is more important in locking the substrate into the conformation leading to Path A than in shieldieng the El+ Fleming, JCS Perkin Trans I, 1992, 3303-3308. El C R SiR3 R' A H R PhMe2Si R Me SiR3 C H H C El C R' H R SiR3 H C A R' R El R R' Me R A Me PhMe2Si C H PhMe2Si O O PhMe PhMe2Si 2Si R R Me R Me R H R SiR3 H C Me PhMe2Si PhMe2Si R Me C A R Me R Me PhMe2Si R' PhMe2Si OH OH OH OH A El A A R R' SiR3 R' 0A-07-Allylsilanes 10/8/00 8:13 PM

A Model for Diastereoselective Hydroborations Dave Evans. Chem 115. Lecture 22 Dec 14. 1993 Diastereoselective Hydroboration EXamples H202 Favored product for J. Am. Chem.Soc.1983,1053725 ThexyIBH2 80: 20 9-BBN 93:07 aA tumover in diastereofacial selectivity is sometimes observed using BH3 nBu OH :08 W. C. Still J BH3THF→nBu ok6 Assume OH (OR)=Rm and results are consistent with the model K N Houk, M. N. Paddon-Row, Co-workers 10A-08-Hydroboration Models 10/8/00 8: 13 PM

K. N. Houk, M. N. Paddon-Row, & Co-workers, Tetrahedron 1984, 40, 2257-2274. Assume OH (OR') = Rm and results are consistent with the model W. C. Still & J. C. Barrish, J. Am. Chem. Soc. 1983, 105, 2487. BH3•THF 9–BBN H2O2 OR' OH OH OTMS OAc OH nBu iPr nBu nBu nBu 92 : 08 96 : 04 91 : 09 88 : 12 42 : 58 R Selectivity R2BH M. M. Midland & Co-workers, J. Am. Chem. Soc. 1983, 105, 3725. H2O2 R2BH Dave Evans, Chem 115, Lecture 22, Dec 14, 1993 BH3 H2O2 H2O2 ■ A turnover in diastereofacial selectivity is sometimes observed using BH3 Favored product for dialkyl borane reagents H H2O2 2O2 R2BH Worse Bad ■ Hydroboration of allylic alcohols (ethers) Selectivity 50 : 50 80 : 20 93 : 07 96 : 04 BH3•DMS ThexylBH2 9–BBN (Chx)2BH Diastereoselective Hydroboration Examples A Model for Diastereoselective Hydroborations OH Me RM OH RL R OR' RL RM Me B H B H H H Me RM Me C H RL H C Me C Me OR' RL R OH R RM H OR' Me OH H H RL RM H C Me C C B B H H H Me RM H RL RM RL RM Me R R R R Me RM RL OH RL RM Me OH H H H C C H H Me H RL Me H H Me Me H H Me H H OH H Me H H Me OH 10A-08-Hydroboration Models 10/8/00 8:13 PM

Diastereoselective Hydroborations Diastereoselective Hydroborations a Erythronolide synthesis: Annette Kim 3 ThexylBH2 ETHF,0° C-art TBSO Et TBsO 797800 9BBN85:1570% BH3THF 05 84% mixture of the lactol lactone I ized to the keto-lactone in a Lonomycin synthesis: Andy Ratz 60%) BH3THF unexpectedly provided the anti isomer in high selectivity 9-BBN Diastereoselection>95: 5(antij r I Anti-selective hydroborations with borane (85%) Diastereoselection 92: 8(syn) I The sense of asymmetric induction is completely turned over in Andy 's reaction when using R2BHeBH3 K Mon Diastereoselection 92: 8(anti) Tetrahedron 1979. 32. 1979 Bull. Chem. Soc. Jpn., 1992, 65, 2974 REH reselection 6.8: 1(anti BH3. DMS 17: 83 Oikawa& Co-workers Tetrahedron Lett, 1983, 19, 1987 reselection 6.6: 1 (anti) 10A-09-Hydroboration-2 10/8/00 8: 13 PM

I. Paterson & J. Channon Tetrahedron Lett., 1992, 33, 797-800. BH3•THF unexpectedly provided the anti isomer in high selectivity 5 anti syn 74% 89% yield 95 : 05 >95 : 05 9-BBN BH3•THF anti : syn anti : syn 9-BBN BH3•THF 85 : 15 05 : 95 yield 70% 84% anti syn 80% 99% yield 82 : 18 17 : 83 (Chx)2BH BH3•DMS anti : syn anti syn The sense of asymmetric induction is completely turned over in Andy's reaction when using R2BH↔BH3 ■ Erythronolide synthesis: Annette Kim Diastereoselection 93 : 7 THF, 0 °C→rt 12 h 3 ThexylBH2 ■ Lonomycin synthesis: Andy Ratz Diastereoselective Hydroborations BH3•DMS (85%) Diastereoselection > 95 : 5 (anti) 9-BBN (60%) Diastereoselection 92 : 8 (syn) Nakata, Tatsuta & Co-workers, Bull. Chem. Soc. Jpn., 1992, 65, 2974. Diastereoselective Hydroborations BH3•THF BH3•THF Diastereoselection 92 : 8 (anti) R = H Diastereoselection 6.8 : 1 (anti) R = OBn Diastereoselection 6.6 : 1 (anti) K. Mori Tetrahedron 1979, 32, 1979. Oikawa & Co-workers Tetrahedron Lett., 1983, 19, 1987. ■ Anti–selective hydroborations with borane A 2:1 mixture of the lactol:lactone was obtained. This mixture was oxidized to the keto-lactone in 73% overall yield from the olefin. Me OH Me H O Me Me OMe Me OMe Me XP O OH OH OH OBn OH Me OBn OH Me O Me OH XP Me OMe Me OMe Me O H Me OH Me Me OH Me H O Me OMe Me OMe Me XP O O Et OH Me O Me TBSO Me Me TBSO Me Me Et O OH O OH Et Me O Me TBSO Me OH OH Me OBn OH Me OH OH Me OH Me OBn OBn OH OBn Me Me OH Me OBn OBn OBn OH Me OH OH OH OH OH OH Me OH OBn OBn Me OBn OH Me Me OBn OH OBn Me OBn OH Me OH Me O O O O Me Me Me Me O BnO R Me Me O O Me R BnO OH Me O Me O O OH 10A-09-Hydroboration-2 10/8/00 8:13 PM