J. Janey The Asymmetric Baylis-Hillman Reaction Chem 206 Possible stereoisomers F R3N Ha H Me Assumptions: NR3: R3N E2 favored over E1 pathway Ha Ha -Nr3 is orthogonal to r face R3NYTyH MeO2C "oH MeO2C 人 Co Me HO.A 120° rotation then e2 elim 25A-0511/9/011:08PM
The Asymmetric Baylis-Hillman Reaction Chem 206 Possible Stereoisomers Hα O H R' H H NR3 + MeO O Hα O R' H H H NR3 + MeO O Hα O H R' + O OMe H R H 3N Hα O R' H + O OMe H R H 3N CO2Me Hα O H R' H H NR3 + CO2Me Hα O R' H H H NR3 + CO2Me Hα O H R' + H R H 3N CO2Me Hα O R' H + H R H 3N H R3N H Hα MeO2C H R3N H Hα MeO2C H H NR3 Hα CO2Me H H NR3 Hα CO2Me R' H OH R' OH H R' HO H R' H HO R' CO2Me OH R' CO2Me OH + + ++ 120 ° rotation then E2 elim. Assumptions: • E enolate formed • E2 favored over E1 pathway • -NR3+ is orthogonal to π face (stereoelectronics) – –– – – – –– J. Janey 25A-05 11/9/01 1:08 PM
J. Janey The Asymmetric Baylis-Hillman Reaction Chem 206 EZ Selectivity with Crotononitrile HcHO 1 eq Solvent EZ ratio 12 EZ ratio 14:1 3-QDL CH3 CN 3.1: 1 NEt3 4 17 h, CHCl 50 vol% 5 moi DABco. 8 kh 17 h solvent 50 vol% the reaction Products did not undergo retro-Baylis-Hillman Rozendaal E L M. Voss. B M. W. Scheeren. H. W. Tetrahedron 1993. 49. 6931-6936 810121416 Pressure(kbar) 5 mol DABCO17h solvent 50 vol% 25A-0611/9/011:08PM
The Asymmetric Baylis-Hillman Reaction Chem 206 E/Z Selectivity with Crotononitrile CN Me PhCHO Ph Me CN OH Ph CN OH Me r.t. + + E Z Solvent neat THF CHCl3 CH3CN MeOH E/Z ratio 1.2 : 1 1.4 : 1 1.5 : 1 3.1 : 1 4 : 1 5 mol% DABCO, 8 kbar, 17 h, solvent 50 vol% Base DABCO 3-QDL NEt3 E/Z ratio 1 : 1 2 : 1 4 : 1 10 mol% base, 8 kbar, 17 h, CHCl3 50 vol% 1 eq 1 eq 5 mol% DABCO,17 h, solvent 50 vol% Rozendaal, E. L. M.; Voss, B. M. W.; Scheeren, H. W. Tetrahedron 1993, 49, 6931-6936. • E and Z crotononitrile is easily isomerized under the reaction conditions. • Products did not undergo retro-Baylis-Hillman. J. Janey 25A-06 11/9/01 1:08 PM