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 new access to enantioenriched compounds starting from the abundant hydrocarbon compounds.

Allyl bromide-enabled diversification of strong C(sp3)-H bonds: From stoichiometric reactions to catalysis

“…The UV-Vis absorption spectra of the individual components and different combinations revealed that all the substrates (2ethylnaphthalene and 1a) and the reactant mixtures ([2-ethylnaphthalene + 1a], [2-ethylnaphthalene + NaF], [1a + NaF], [2-ethylnaphthalene + 1a + NaF]) only showed absorption at λ < 330 nm. When they were stirred for 6 h however, an obvious red-shift was observed in the mixture of NaF and 1a, but not in the other components or the product (27). These outcomes supported the hypothesis that the visible-lightresponding species might be derived from slow complexation of NaF with the allyl bromide (1a).…”

Recent Advances in Asymmetric Transformations of Unactivated Alkanes and Cycloalkanes through Direct C—H Functionalization

“…We found that a three‐component reaction of a cycloalkane (or any other inactive C(sp 3 )–H precursor), a SO 2 surrogate ( 22 ) and the reaction of a common α,β ‐unsaturated carbonyl compound ( 23 ) could be effectively catalyzed by the combination of an HAT photocatalyst ( PC1 ) with a chiral nickel catalyst of a bisoxazoline ligand ( L2 ), delivering biologically interesting α ‐carbon chiral sulfones with up to >50 : 1 rr and 62%—95% ee (Scheme 14). [ 71 ] A wide variety of cycloalkanes, alkanes, benzylic or allylic hydrocarbons and ethers were tolerated under the mild reaction conditions. For example, the reaction of cyclododecane gave the desired product ( 24a ) in 65% yield and with 91% ee , while that of 1‐ethyladamantane or isopentane afforded 24b or 24c as a single reigoisomers with 87% or 80% ee , respectively.…”

Chiral polycyclic benzosultams from photocatalytic diastereo- and enantioselective benzylic C–H functionalization

“…In our recent studies, cooperative systems of a chiral 3d metal catalyst and an organophotocatalyst have been established to be useful for the enantioselective addition of C(sp 3 )-H precursors to prochiral substrates. 40,41 However, these systems have not shown any success in directly installing stereocenters on the cleaved C-H bonds, termed as 'enantioselective C(sp 3 )-H functionalization'. To address this long-standing problem, we chose toluene derivatives bearing a chlorine group at the γ-position as the substrate.…”