Bidirectional Iterative Approach to Sequence-Defined Unsaturated Oligoesters

[Image: see text] Herein, we describe the development of a new strategy for the synthesis of unsaturated oligoesters via sequential metal- and reagent-free insertion of vinyl sulfoxonium ylides into the O–H bond of carboxylic acid. Like two directional coupling of amino acids (N- to C-terminal and C- to N-terminal) in peptide synthesis, the present approach offers a strategy in both directions to synthesize oligoesters. The sequential addition of the vinyl sulfoxonium ylide to the carboxylic acids (acid iteration sequence) in one direction and the sequential addition of the carboxylic acids to the vinyl sulfoxonium ylide (ylide iteration sequence) in another direction yield (Z)-configured unsaturated oligoesters. To perform this iteration, we have developed a highly regioselective insertion of vinyl sulfoxonium ylide into the X–H (X = O, N, C, S, halogen) bond of acids, thiols, phenols, amines, indoles, and halogen acids under metal-free reaction conditions. The insertion reaction is applied to a broad range of substrates (>50 examples, up to 99% yield) and eight iterative sequences. Mechanistic studies suggest that the rate-limiting step depends on the type of X–H insertion.