Organocatalyzed Rearrangement of S-(2-Oxoalkyl)-thioenoates

Abstract

The highly Lewis basic amidine-based catalyst DHIP promotes the rearrangement of S-phenacyl thiocinnamate and related thioesters into dihydrothiophene derivatives. In contrast to previously explored rearrangements of thioesters, the reaction proceeds via a novel Dieckmann-like cyclization pathway. An alternative two-component synthesis of the same products has also been developed.

Cascade Cyclizations of α,β-Unsaturated Thioesters: Additional Examples

“…Two mechanistic scenarios are outlined in Figure : Pathway A, which requires covalent Lewis base catalysis, and Pathway B, which relies on a chain reaction initiated by free thiolate. Four examples of reactions of this type illustrated in Figure have been reported by Matsubara (eq 1), our group (eqs 2–4, see Figure for structures of catalysts), and Xu (eq 3) . While reactions shown in eqs 2 and 3 clearly proceed via Pathway A to provide the products in optically pure form, the enantioselective formation of lactone 2 in eq 1 can be rationalized as occurring via either pathway.…”

Isothiouronium-Mediated Conversion of Carboxylic Acids to Cyanomethyl Thioesters

“…Considering approaches described for, e.g., cyanomethyl thioesters (Scheme B), esterification of thiols is the most common strategy, with classical methods relying on the activation of carboxylic acids (via acid chlorides or anhydrides). Recently, thioester syntheses employing photoredox catalysis have also been developed. − Although transition-metal-catalyzed approaches have been described, functional group tolerance remains a challenge in these variants. , Thiocarboxylic acids also feature as suitable starting materials for thioester synthesis, either by reaction with an alkyl halide − or coupling to a Michael acceptor. , Nevertheless, thiols and thiocarboxylic acids suffer from limited commercial availability and are prone to oxidative dimerization (Scheme B) …”