Efficient synthesis of novel gamma-substituted gamma-butenolides by Lewis acid catalyzed addition of metal enolates of active methylene compounds to mucohalic acids.

Lewis acid catalyzed addition of active methylene compounds to mucochloric acid (1) and mucobromic acid (2) affording Knoevenagel aldol adducts, gamma-substituted gamma-butenolides, has been explored. Catalytic efficiencies of various Lewis acids have been compared. Indium acetate (0.25-5 mol %) was found to be the most efficient catalyst.

Further utilization of mucohalic acids: palladium-free, regioselective etherification and amination of alpha,beta-dihalo gamma-methoxycarbonyloxy and gamma-acetoxy butenolides.

Palladium-free etherification and amination of mucohalic acid methyl carbonates 1e (3,4-dichloro-5-methoxycarbonyloxy-5H-furan-2-one) and 1f (3,4-dibromo-5-methoxycarbonyloxy-5H-furan-2-one) and mucochloric acid acetate 1h (3,4-dichloro-5-acetoxy-5H-furan-2-one) was achieved to afford gamma-functionalized alpha,beta-unsaturated gamma-butyrolactones in good to excellent yield. [reaction: see text]

Reinvestigation of mucohalic acids, versatile and useful building blocks for highly functionalized alpha,beta-unsaturated gamma-butyrolactones.

[reaction: see text] Mucohalic acids (mucochloric acid (1, 3,4-dichloro-5-hydroxy-5H-furan-2-one) and mucobromic acid (2, 3,4-dibromo-5-hydroxy-5H-furan-2-one)) are inexpensive, commercially available starting materials with multiple functional groups. These compounds have been modified by way of reduction followed by Suzuki cross-coupling reactions involving arylboronic acids to afford highly functionalized alpha,beta-unsaturated gamma-butyrolactones in excellent yield. The synthetic utility of these building blocks was effectively demonstrated through preparation of the antiinflammatory drug Vioxx.