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