Asymmetric Synthesis of α‑Branched Amines via Rh(III)-Catalyzed C–H Bond Functionalization

The first asymmetric intermolecular addition of non-acidic C–H bonds to imines is reported. The use of the activating <i>N</i>-perfluorobutanesulfinyl imine substituent is essential for achieving sufficient reactivity and provides outstanding diastereoselectivity (>98:2 dr). Straightforward removal of the sulfinyl group with HCl yields the highly enantiomerically enriched amine hydrochlorides

Asymmetric Synthesis of α‑Branched Amines via Rh(III)-Catalyzed C–H Bond Functionalization

The first asymmetric intermolecular addition of non-acidic C–H bonds to imines is reported. The use of the activating <i>N</i>-perfluorobutanesulfinyl imine substituent is essential for achieving sufficient reactivity and provides outstanding diastereoselectivity (>98:2 dr). Straightforward removal of the sulfinyl group with HCl yields the highly enantiomerically enriched amine hydrochlorides

Preparation of Enantiomerically Pure Perfluorobutanesulfinamide and Its Application to the Asymmetric Synthesis of α‑Amino Acids

A high yielding and practical two-step synthesis of enantiomerically pure perfluorobutanesulfinamide from Senanayake’s 2-aminoindanol-derived sulfinyl transfer reagent was developed and carried out on a multigram scale. Straightforward condensation of this sulfinamide with ethyl glyoxylate provided the <i>N</i>-perfluorobutanesulfinyl imino ester. The utility of this activated <i>N</i>-sulfinyl imino ester was demonstrated for reactions that gave either no product or very low yields with the corresponding less electrophilic <i>N</i>-<i>tert</i>-butanesulfinyl derivative. Specifically, the Rh­(III)-catalyzed C–H bond addition of aromatic compounds to the <i>N</i>-perfluorobutanesulfinyl imino ester provided arylglycines with very high diastereoselectivities for a range of directing groups including pyrrolidine amide, azo, sulfoximine, 1-pyrazole, and 1,2,3-triazole functionalities. Thermal asymmetric aza-Diels–Alder reactions also proceeded in good yields and with high selectivity, including for the substituted dienes (<i>E</i>)-1,3-pentadiene and (2<i>E</i>,4<i>E</i>)-2,4-hexadiene