An organic thiyl radical catalyst for enantioselective cyclization

Abstract

A diverse array of chiral organocatalysts have been developed that rely on acid-base interactions to promote enantioselective ionic reactions via the movement of electron pairs. The stereocontrol of radical reactions using organocatalysts is an alternative approach, and several studies have shown that synthetically useful reactivity can result by controlling the movement of single electrons. However, in these studies, it is still an acid-based organocatalyst which forms a closed-shell intermediate with substrate prior to the radical reaction and imparts chiral information, and use of a chiral organic radical directly as catalyst has only rarely been explored. Here, we report the design of an organic thiyl radical catalyst with a carefully designed chiral pocket constructed around a chiral thiol precatalyst. The resulting catalyst was used to effect highly diastereo- and enantioselective C-C bond-forming radical cyclizations.

Photochemical Stereocontrol Using Tandem Photoredox–Chiral Lewis Acid Catalysis

“…Although several different strategies for highly enantioselective cycloadditions of cyclopropanes have been reported, all of these have involved highly activated donor–acceptor cyclopropanes 44,45,46 or vinylcyclopropanes. 47,48 The method developed in our laboratory, however, works well for a variety of electronically dissimilar cyclopropyl ketones, affording cycloadducts arising from cyclopropanes bearing either alkyl or ester β-substituents ( 38 – 41 ). Finally, Figure 6 depicts a third enantioselective photocatalytic method developed in our laboratory that exploits a two-catalyst strategy in the context of a conjugate addition reaction of an α-silylamine pronucleophile ( 43 ) to a β-substituted Michael acceptor ( 44 ).…”

Rhodium(iii)-catalyzed C–H/C–C activation sequence: vinylcyclopropanes as versatile synthons in direct C–H allylation reactions

“…1a). 12 Alternatively, the direct oxidative addition of cyclopropane to a low-valent nucleophilic transition metal to form a p-allyl metal complex as the key reaction intermediate is also a literature precedent (Fig. Because of the chemical inertness of the C-C single bond, b-carbon elimination is generally unfavored and thus far less established, 8 even though the selective C-C cleavage has attracted increasing interest in the synthetic community, as it offers a potential alternative for synthetic disconnection.…”

The Design of Environmentally-Benign, High-Performance Organocatalysts for Asymmetric Catalysis

“…In 2014, we developed novel, chiral organic thiyl radical catalysts based on the indanol unit for the highly diastereo and enantioselective radical [3 2] cyclization between vinylcyclopropanes and alkenes. 43 Our initial attempts using binaphthyl based chiral disul de or thiol catalysts failed to give high enantioselectivity of product (up to 40% ee). Thus, our attention was turned to designing a novel, chiral thiyl radical catalyst.…”