Sulfenate Substitution as a Complement and Alternative to Sulfoxidation in the Diastereoselective Preparation of Chiral β-Substituted β-Amino Sulfoxides

Building from a previous communication, the reaction of sulfenate anions with chiral N-Boc-protected beta-substituted beta-amino iodides was evaluated as a conceptually different synthetic approach to chiral beta-substituted beta-amino sulfoxides. Using arenesulfenates, yields typically ranged from 71% to 92%, and dr's were often near 9:1. Alkanesulfenates proved less reactive, delivering lower yields and dr's. 1-Alkenesulfenates demonstrated high reactivity, returning chemical yields of 60-86% and dr's often close to 9:1 and as high as 95:5. (S)-beta-Amino iodide electrophiles yielded (R-S,S-C)-beta-amino sulfoxides, whereas (R)-amino iodides afford (S-S,R-C)-beta-amino sulfoxides. The absolute configuration of the products makes the sulfenate protocol complementary to other existing preparations, including the commonly employed sulfoxidation of beta-amino sulfides. The reactivity of N-Boc-protected 2-benzyl-2-aminoethyl iodide was found to be superior to the less sterically encumbered n-butyl iodide. A transition state model is proposed to account for the stereochemistry of the products and also for the high reactivity of the electrophile. Overall, the chemistry represents a new means of introducing sulfur stereogenicity in a molecule.