2 -Benzofuranones, 3-acyl

Analogous rearrangements have also been performed by both Fu [73] and Vedejs [105] on (9-acyl benzofuranones and (9-acyl oxindoles to provide synthetic intermediates potentially suitable for elaboration to diazonamide A and various oxin-dole-based alkaloids such as gelsemine respectively. Peris has also examined both Fu s and Vedejs chiral 4-DMAP catalysts for effecting diastereoselective carboxyl migrations of 3-arylbenzofuranones [109]. 

Amino-2,3-dihydrobenzofurans such as (501) and (502) are useful as antidepressants and hypotensives (70USP3513239). Substituted 5-acyl-2,3-dihydrobenzofuran-2-carboxylic acids of the type (503) possess diuretic and antitussive activities (69GEP1927393). Derivatives of the 3-phenyl-2 (3H)-benzofuranone type (504) exhibit musculotropic and anaesthetic effects. Amethone (505) is used against bronchial asthma and also shows antihistaminic activity (47JA980). 

Rearrangement of O-Acyl Azlactones, O-Acyl Oxindoles, and O-Acyl Benzofuranones... 

Construction of quaternary stereocenters by enantiocontrolled oxygen to carbon acyl shift is not limited to the azlactone structure. Using the pentaphenylated planar chiral DMAP derivative 79c (Scheme 13.42) Fu and Hills achieved rearrangement of O-acylated oxindoles 84 (Scheme 13.45) and benzofuranones 85 (Scheme 13.46) with very good yields and enantiomeric excesses up to 99% [88]. 

This chapter summarizes three related and highly effective approaches to the catalytic asymmetric generation of quaternary stereocenters - organocatalytic rearrangements of O-acyl azlactones to their C-acylated isomers and analogous isomer-izations of O-acyl oxindoles and O-acyl benzofuranones. All three processes hold great promise for application in, e.g., natural product synthesis [91-93],... 

Additions to prochiral ketenes [13.2] Desymmetrization of meso-diols [13.3] Dynamic kinetic resolution of azlactones rearrangement of O-acyl azlactones, O-acyl oxindoles, O-acyl benzofuranones [13.6]... 

Chromatography) (equation 82). These complexes are used as enantioselective nucleophilic catalysts for reactions such as the rearrangements of O-acylated azlactones, oxindoles, and benzofuranones, and the kinetic resolution of secondary alcohols via acylation. X-ray crystal structures have been obtained for iV-acylated derivatives of (366), allowing for characterization of a likely intermediate along the catalytic pathway. 

Another route to C-acylation is illustrated in Scheme 62. The benzofuranone (154) on reaction with methyl chloroformate in the presence of LDA gave the 0-acylated product (155) in 88% yield. With methyl cyanoformate, the C acylated product (156) was obtained in 94% yield. However, the larger scale use of this reagent was unsatisfactory, so an alternative strategy was devised. The ketone (154) was treated with carbon disulfide, dimethyl sulfate and base in DMSO to give the bis(methylthio) ketene acetal. Aqueous base yielded the C-acylated product (156) in 83% overall yield. 

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