| 15214082 |
Rayabarapu DK, Chang HT, Cheng CH: Synthesis of phthalide derivatives using nickel-catalyzed cyclization of o-haloesters with aldehydes. Chemistry. 2004 Jun 21;10(12):2991-6.
The reaction of o-bromobenzoate (1 b) with benzaldehyde (2 a) in the presence of [NiBr (2)(dppe)] (dppe=1,2-bis (diphenylphosphino) ethane) and zinc powder in THF (24 hours, reflux temperature), afforded 3-phenyl-3H-isobenzofuran-1-one (3 a) in an 86 % yield. Similarly, o-iodobenzoate reacts with 2 a to give 3 a, but in a lower yield (50 %). A series of substituted aromatic and aliphatic aldehydes (2 b, 4-MeC (6) H (4) CHO; 2 c, 4-MeOC (6) H (4) CHO; 2 d, 3-MeOC (6) H (4) CHO; 2 e, 2-MeOC (6) H (4) CHO; 2 f, 4-CNC (6) H (4) CHO; 2 g, 4-(Me)(3) CC (6) H (4) CHO; 2 h, 4-C (6) H (5) C (6) H (4) CHO; 2 i, 4-ClC (6) H (4) CHO; 2 j, 4-CF (3) C (6) H (4) CHO; 2 k, CH (3)(CH (2))(5) CHO; 2 l, CH (3)(CH (2))(2) CHO) also underwent cyclization with o-bromobenzoate (1 b) producing the corresponding phthalide derivatives in moderate to excellent yields and with high chemoselectivity. Like 1 b, methyl 2-bromo-4,5-dimethoxybenzoate (1 c) reacts with tolualdehyde (2 b) to give the corresponding substituted phthalide 3 m in a 71 % yield. The methodology can be further applied to the synthesis of six-membered lactones. The reaction of methyl 2-(2-bromophenyl) acetate (1 d) with benzaldehyde under similar reaction conditions afforded six-membered lactone 3 o in a 68 % yield. A possible catalytic mechanism for this cyclization is also proposed. |
31(0,1,1,1) |