Bidirectional Iterative Approach to Sequence-Defined Unsaturated Oligoesters

Abstract

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.

Stereoselective gem-Difunctionalization of Diazo Compounds with Vinyl Sulfoxonium Ylides and Thiols via Metalloradical Catalysis

“…Experimental procedures for all reactions and characterization data for all products, including 1 H, 19 F, and 13 C NMR spectra; crystal data; and DFT calculations (PDF) X-ray crystallographic data of 4n (CIF)…”

“…Between these two carbene precursors, diazo compounds react faster under metal-catalyzed conditions than sulfoxonium ylides and generate a reactive electrophilic carbene intermediate, which is then trapped by sulfoxonium ylide as a nucleophile. Prompted by this observation and our continuing interest in sulfoxonium ylides, − we were intrigued to obtain stereoselective gem -difunctionalization of diazo compounds with the thiols and sulfoxonium ylides to obtain tertiary sulfide compounds, which are basic scaffolds for various natural products and medicinally important compounds. , …”

Insights into the multifaceted applications of vinyl sulfoxonium ylides

“…[27][28][29] Recently, our group synthesized g-functionalized a,bunsaturated carbonyl compounds via regioselective X-H (X = C, N, O, S, halogen) insertion of vinyl sulfoxonium ylides under metal-free conditions (Scheme 5). 30 Due to the presence of carbonyl and olefinic functional groups, they can be utilized as basic building blocks for various organic transformations.…”

Ir(I)-Catalyzed Synthesis of Furanones from Vinyl Sulfoxonium Ylides

“…Sulfoxonium ylides are a safe alternative to diazo reagents due to their high thermal stability, and their utility has been demonstrated in large-scale reactions . Thus, our group developed metal-catalyzed carbenoid transformation from sulfoxonium ylides and applied it to the synthesis of various heteroarenes and arenes. , Here in, we report the one-pot synthesis of 4-aryl-2­(5 H )-furanones from in situ generated vinyl sulfoxonium ylides via carbonyl ylide mediated rearrangement (Scheme b).…”