Synthesis of Phthalide Derivatives Using Nickel‐Catalyzed Cyclization of o‐Haloesters with Aldehydes

Publisher Website
Google Scholar
Abstract
The reaction of o‐bromobenzoate (1 b) with benzaldehyde (2 a) in the presence of [NiBr2(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‐MeC6H4CHO; 2 c, 4‐MeOC6H4CHO; 2 d, 3‐MeOC6H4CHO; 2 e, 2‐MeOC6H4CHO; 2 f, 4‐CNC6H4CHO; 2 g, 4‐(Me)3CC6H4CHO; 2 h, 4‐C6H5C6H4CHO; 2 i, 4‐ClC6H4CHO; 2 j, 4‐CF3C6H4CHO; 2 k, CH3(CH2)5CHO; 2 l, CH3(CH2)2CHO) 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.

This publication has 43 references indexed in Scilit: