carboxylic acids or acid derivatives are produced. The named reactions are differentiated by the substrates involved, subtle variances in mechanism, or the products obtained. Coincidentally, all three methods appear to have become “named reactions” through third party classification of each reaction by its respective discoverer(s) in separate 1998 publications.4 In the Jocic-Reeve and Corey-Link reactions, the intermediate gem-dichloroepoxides are formed in situ by treatment of readily accessible trichloromethyl carbinols (2) with base in protic or mixed media (Scheme 1). Nucleophiles readily undergo regioselective substitution at the .-carbon (non-chloride bearing position) of the oxiranes (4) leading to formation of .-substituted acid chlorides (5). The acid chlorides are subject to nucleophilic acyl substitution, including solvolysis, affording a variety of possible carboxylic acid derivatives (6) or heterocycles depending upon the reaction conditions used. Product yields are typically high, although alternative reaction paths are known to compete upon slight modifications of reaction conditions.5 Scheme 1. General mechanism of reactions involving gem-dichloroepoxides (4). The Corey-Link reaction is a specific example of the much broader and more general Jocic- Reeve reaction. In the Corey-Link approach, asymmetric trichloromethyl carbinols are treated with azide to from chiral .-azido carboxylic acid derivatives.2 These products are often subsequently reduced to furnish unnatural .-amino acids in high yields. The Corey-Link reaction is arguably the most popular and recognizable of the reactions involving gem-dichloroepoxide intermediates. Whereas Jocic-Reeve and commonly, although not exclusively, Corey-Link reactions begin by treating secondary trichloromethyl carbinols (2 where R1 or R2 = H) with base, the Bargellini reaction typically involves addition of a sterically accessible ketone to trichloromethide (formed by deprotonation of added chloroform with hydroxide or DBU) resulting in an .-trichloromethyl tertiary alkoxide (3). The alkoxide rapidly forms the gem-dichloroepoxide (4) without necessitating isolation of the carbinol 2 (Scheme 1). A key application of this reaction is the preparation of hindered .-substituted carboxylic acid derivatives that may be difficult to prepare by direct nucleophilic substitution with congested 2-halocarboxylic acid derivatives. The reaction sequence from intermediate 3 to product 6 highlighted in Scheme 1 is synthetically attractive for several reasons: 0
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