Intermolecular sp3-C–H Amination for the Synthesis of Saturated Azacycles

The preparation of substituted azetidines and larger-ring, nitrogen-containing saturated heterocycles is enabled through efficient and selective intermolecular sp³-C–H amination of alkyl bromide derivatives. A range of substrates is demonstrated to undergo C–H amination and subsequent sulfamate alkylation in good to excellent yield. N-Phenoxysulfonyl-protected products can be unmasked under neutral or mild basic conditions to yield the corresponding cyclic 2° amines. The preparative convenience of this protocol is demonstrated through gram-scale and telescoped multi-step procedures. Application of this technology is highlighted in a nine step total synthesis of an unusual azetidine-containing natural product, penaresidin B.