Photocatalytic three-component asymmetric sulfonylation via direct C(sp3)-H functionalization

Abstract

The direct and selective C(sp3)-H functionalization of cycloalkanes and alkanes is a highly useful process in organic synthesis owing to the low-cost starting materials, the high step and atom economy. Its application to asymmetric catalysis, however, has been scarcely explored. Herein, we disclose our effort toward this goal by incorporation of dual asymmetric photocatalysis by a chiral nickel catalyst and a commercially available organophotocatalyst with a radical relay strategy through sulfur dioxide insertion. Such design leads to the development of three-component asymmetric sulfonylation involving direct functionalization of cycloalkanes, alkanes, toluene derivatives or ethers. The photochemical reaction of a C(sp3)-H precursor, a SO2 surrogate and a common α,β-unsaturated carbonyl compound proceeds smoothly under mild conditions, delivering a wide range of biologically interesting α-C chiral sulfones with high regio- and enantioselectivity (>50 examples, up to >50:1 rr and 95% ee). This method is applicable to late-stage functionalization of bioactive molecules, and provides an appealing access to enantioenriched compounds starting from the abundant hydrocarbon compounds.

Decatungstate-Catalyzed C(sp3)–H Sulfinylation: Rapid Access to Diverse Organosulfur Functionality

“…The importance of these ubiquitous motifs is underscored by their abundance in bioactive molecules, with sulfur being more commonly found than fluorine or phosphorus in approved drugs . Despite the well-established importance of organosulfur compounds and many advances in C–H functionalization, there remain few catalytic technologies for the conversion of C­( sp 3 )–H bonds into alkylsulfonyl groups . Intriguingly, recent studies involving alkyl sulfinates have instead focused on the inverse transform, namely C­( sp 3 )–SO 2 bond cleavage via the oxidative conversion of sulfinates to alkyl radicals with concomitant extrusion of SO 2 .…”

Access to chiral β-sulfonyl carbonyl compounds via photoinduced organocatalytic asymmetric radical sulfonylation with sulfur dioxide

“…The absolute configuration of 5a was assigned as S by comparison with Gong's work. 9 Additionally, both primary and secondary potassium alkyltrifluoroborates worked well and delivered the target products 5j–5q in 31–80% yields with 80–95% ee.…”

“…8 Recently, Gong and co-workers demonstrated a photoinduced asymmetric sulfonyl radical addition to a,b-unsaturated carbonyl compounds under chiral nickel catalysis. 9 The sulfonyl radical was generated in situ from the reaction of the C(sp 3 )-H precursor and All publication charges for this article have been paid for by the Royal Society of Chemistry DABCO$(SO 2 ) 2 in this transformation. Despite signicant advances, the aforementioned metal-catalyzed radical additions still suffer from substrate limitations, where the coordination of an auxiliary group to the metal center is essential for substrate activation and stereochemical control.…”

Multicomponent reactions and photo/electrochemistry join forces: atom economy meets energy efficiency

“…This year, the three-component asymmetric radical sulfonylation of a,b-unsaturated carbonyl compounds employing cyclic and acyclic alkanes, toluene derivatives, and ethers was accomplished. 304 More than 50 examples were prepared, showing up to 50 : 1 rr and 95% ee. Radical generation was obtained through the use of 5,7,12,14-pentacenetetrone as a photocatalyst, DABSO as SO surrogate, and a nickel catalyst with a chiral bisoxazoline ligand.…”