Thiiranes — the sulfur-containing counterpart to epoxides — are useful compounds, although they are somewhat difficult to synthesize. With ring strain on the order of 18 kcal mol−1, they can be readily opened to furnish sulfurous organic molecules or polymerized to form high-refractive-index polymers. This ring-strain, while also giving rise to intriguing biological activity, brings with it instability, and methods to synthesize these feisty molecules are limited — unlike their oxygenated brethren. Routes to thiiranes often require harsh reaction conditions that are not amenable to asymmetric synthesis. However, Ben List and co-workers from the Max Planck Institute have developed a method that bypasses both of these limitations with some clever catalysis (J. Am. Chem. Soc. 138, 5230–5233; 2016).

Rather than form the thiirane directly from an olefin or similar, List and co-workers suggest instead starting with the far more accessible epoxides. Noting that thiolactams undergo an exchange reaction with epoxides under acidic conditions — yielding a thiirane and a lactam — the group used chiral phosphoric acid derivatives bearing bulky triisopropylphenyl groups (TRIP, see figure) to enable a kinetic resolution strategy for the reaction. Because TRIP engages in hydrogen bonding with the thiolactam in a heterodimeric resting state, as observed by in situ NMR, the epoxide is directed preferentially to one face of the catalyst. As a result, one enantiomer of the racemic epoxide starting material reacts more rapidly than the other and the products of the reaction are the enantioenriched thiirane and epoxide of opposite handedness, with an average enantiomeric ratio exceeding 97:3.

Owing to the hindered chiral pocket around the acidic phosphate group of TRIP and the low catalyst loading (0.1 mol%), this method avoids some of the undesired side reactions that typically characterize the acid-catalysed exchange reactions that produce thiiranes. As a result, the reaction has a broad substrate scope, accommodating a wide variety alkyl and aryl substituents on the parent epoxide. List and co-workers suggest that more convenient access to chiral thiiranes will inspire investigation into their use in synthesis, materials and medicine, where substitution of sulfur in place of oxygen could have dramatic effects on the properties of the product.