Practical and Highly Selective Sulfur Ylide-Mediated Asymmetric Epoxidations and Aziridinations Using a Cheap and Readily Available Chiral Sulfide: Extensive Studies To Map Out Scope, Limitations, and Rationalization of Diastereo- and Enantioselectivities

The chiral sulfide, isothiocineole,
has been synthesized in one
step from elemental sulfur, γ-terpinene, and limonene in 61%
yield. A mechanism involving radical intermediates for this reaction
is proposed based on experimental evidence. The application of isothiocineole
to the asymmetric epoxidation of aldehydes and the aziridination of
imines is described. Excellent enantioselectivities and diastereoselectivities
have been obtained over a wide range of aromatic, aliphatic, and α,β-unsaturated
aldehydes using simple protocols. In aziridinations, excellent enantioselectivities
and good diastereoselectivities were obtained for a wide range of
imines. Mechanistic models have been put forward to rationalize the
high selectivities observed, which should enable the sulfide to be
used with confidence in synthesis. In epoxidations, the degree of
reversibility in betaine formation dominates both the diastereoselectivity
and the enantioselectivity. Appropriate tuning of reaction conditions
based on understanding the reaction mechanism enables high selectivities
to be obtained in most cases. In aziridinations, betaine formation
is nonreversible with semistabilized ylides and diastereoselectivities
are determined in the betaine forming step and are more variable as
a result.