Advances in the stereoselective synthesis of antifungal agents and ...

Chapter 4 90Entry Substrate Config.(ee%)R1 R2 Product(Yield%)Config. Pro(% ee)1 31a - H H 33a (45) -2 31b - H nC 7 H 15 33b (98) -3 (±)-31c - Me nC 6 H 13 (±)-33c(70) -4 (-)-31c R (99) Me nC 6 H 13 (+)-33c(65) S (97)5 (+)-31c S (99) Me nC 6 H 13 (-)-33c(67) R (97)6 (±)-31d - Me Bn (±)33d(40) -7 (-)-31d R (99) Me Bn (+)33d(39) S (98)8 (±)-31e - Et Ph (±)-33e(55) -9 (+)-31e R (99) Et Ph (-)33e(55) S (41)10 31 f - Ph Ph 33f (94) -11 (±)-27a - Ph 4PhC6H4 (±)-33g(96) -12 (+)-27a nd(>95) Ph 4PhC6H4 (±)-33g(96) R,S (0)13 (±)-27b - Ph 2BrC6H4 (±)-33h(81) -14 (+)-27b nd(>95) Ph 2BrC6H4 (±)-33h(96) R,S (0)15 (±)-27c - 2BrC 6 H 4 4PhC6H4 (±)-33i(82) -16 (+)-27c nd(>95) 2BrC 6 H 4 4PhC6H4 (±)-33i86) R,S (0)17 (±)-27g - 2Benzo[b] Ph (±)-33l(10) -furane18 (±)-27m - 2Benzo[b]furane19 (+)-27m nd>60 2Benzo[b]furane2,4C 6 H 3 (±)33m(5) -2,4C 6 H 3 (±)33m(5) R,S (0)Table 4.1: Mitsunobu reaction of alcohols 31a-f and 27a-c,e,g,m with 4,5-dicyanoimidazole.The experimental results led to the following, very importantinformations:1) The reaction did not occur when a tertiary alcohol (e.g. t-butanol)was used as substrate, even if an excess of reagent was used.2) When the diaryl methanoles (entries 10-16) were used as substrateslonger reaction times and an excess of reagents (4:1 molar ratioreagents/substrate) were required in order to achieve complete conversion.When in this class of compounds one aromatic ring was substituted with 2-