Sulfoximines are increasingly incorporated
in agrochemicals
and
pharmaceuticals, with the two enantiomers of chiral sulfoximines often
having profoundly different binding interactions with biomolecules.
Therefore, their application to drug discovery and development requires
the challenging preparation of single enantiomers rather than racemic
mixtures. Here, we report a general and fundamentally new asymmetric
synthesis of sulfoximines. The first S-alkylation
of sulfenamides, which are readily accessible sulfur compounds with
one carbon and one nitrogen substituent, represents the key step.
A broad scope for S-alkylation was achieved by rhodium-catalyzed
coupling with diazo compounds under mild conditions. When a chiral
rhodium catalyst was utilized with loadings as low as 0.1 mol %, the S-alkylation products were obtained in high yields and with
enantiomeric ratios up to 98:2 at the newly generated chiral sulfur
center. The S-alkylation products were efficiently
converted to a variety of sulfoximines with complete retention of
stereochemistry. The utility of this approach was further demonstrated
by the asymmetric synthesis of a complex sulfoximine agrochemical.
Despite their broad utility, the synthesis of ortho‐quinones remains a significant challenge, in particular, access to electron‐deficient derivatives remains an unsolved problem. Reported here is the first general method for the synthesis of electron‐deficient ortho‐quinones by direct oxidation of phenols. The reaction is enabled by a novel bidentate nitrogen‐ligated iodine(V) reagent, a previously unexplored class of compounds which we have termed Bi(N)‐HVIs. The reaction is extremely general and proceeds with excellent regioselectivity for the ortho over para isomer. Functionalization of the ortho‐quinone products was examined, resulting in a facile one‐pot synthesis of catechols, as well as the incorporation of a variety of heteroatom nucleophiles. This method represents the first synthetic application of Bi(N)‐HVIs and demonstrates their potential as a platform for the further development of highly reactive, but also highly tunable, I(V) reagents.
Despite their broad utility, the synthesis of ortho‐quinones remains a significant challenge, in particular, access to electron‐deficient derivatives remains an unsolved problem. Reported here is the first general method for the synthesis of electron‐deficient ortho‐quinones by direct oxidation of phenols. The reaction is enabled by a novel bidentate nitrogen‐ligated iodine(V) reagent, a previously unexplored class of compounds which we have termed Bi(N)‐HVIs. The reaction is extremely general and proceeds with excellent regioselectivity for the ortho over para isomer. Functionalization of the ortho‐quinone products was examined, resulting in a facile one‐pot synthesis of catechols, as well as the incorporation of a variety of heteroatom nucleophiles. This method represents the first synthetic application of Bi(N)‐HVIs and demonstrates their potential as a platform for the further development of highly reactive, but also highly tunable, I(V) reagents.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.