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 β-substituted
β-amino iodides was evaluated as a conceptually different synthetic
approach to chiral β-substituted β-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)-β-Amino
iodide electrophiles yielded (RS,SC)-β-amino sulfoxides, whereas (R)-amino iodides afford (SS,RC)-β-amino sulfoxides. The absolute configuration
of the products makes the sulfenate protocol complementary to other
existing preparations, including the commonly employed sulfoxidation
of β-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.