A highly efficient methodology of asymmetric epoxidation based on a novel chiral sulfur ylide

Abstract

A new type of chiral sulfur ylides has been synthesized and their reactivities against carbonyl compounds tested, showing a high degree of stereoselectivity in the formation of trans epoxy amides under very mild reaction conditions.

Towards a General Understanding of Carbonyl‐Stabilised Ammonium Ylide‐Mediated Epoxidation Reactions

“…To prove that betaine formation is indeed a reversible process, we carried out crossover experiments in analogy to previous studies on sulfur ylides by the group of Aggarwal. [3f] When reacting the racemic syn and anti β-hydroxy ammonium salts 6 with an excess of a more reactive aldehyde, such as p -chlorobenzaldehyde, we found that only the trans epoxides 3 are formed (Scheme 2). In addition, the more reactive aldehyde is incorporated predominantly, giving 90% of the corresponding epoxide starting from syn- 6 and 85% starting from anti - 6 as precursor.…”

“…Aggarwal et al have carefully investigated the energy profile for epoxidation reactions of amide-stabilised sulfur ylides in the past and it was found that hereby also the elimination step is the selectivity-determining step. [3f] To elucidate the reactivity difference between ammonium and sulfonium ylide-mediated epoxidation reactions we thus re-addressed this transformation (considering inclusion of entropic and thermal contributions and a dispersion correction, which were not included previously[3f]). Our calculations clearly confirm the earlier conclusions by Aggarwal et al[3f] that indeed the ring closure is the selectivity-determining step when using amide-stabilised sulfonium ylides.…”

“…[3f] To elucidate the reactivity difference between ammonium and sulfonium ylide-mediated epoxidation reactions we thus re-addressed this transformation (considering inclusion of entropic and thermal contributions and a dispersion correction, which were not included previously[3f]). Our calculations clearly confirm the earlier conclusions by Aggarwal et al[3f] that indeed the ring closure is the selectivity-determining step when using amide-stabilised sulfonium ylides. As it can be seen in Figure 2, the over-all energy profile for the epoxidation mediated by the sulfur ylide 7a is energetically lower than for the one mediated by the ammonium ylide 1a (green vs. blue pathway in Figure 2).…”

“…[1–4] Among the different classes of onium ylides that can be used for such three-ring-forming reactions, sulfur ylides have been the most frequently used ones, and a variety of applications by using achiral or chiral sulfur ylides (either preformed or generated in situ with catalytic quantities of a chiral sulfide) have been reported since. [3] In contrast to the privileged use of sulfonium ylides, easily available ammonium ylides have been less routinely employed in the past. [5–10] Especially, the use of chiral amines to render such reactions enantioselective has so far mainly been limited to cyclopropanation reactions, a methodology that was impressively developed by Gaunt et al[5] However, their use in asymmetric epoxidation and aziridination reactions was found to be rather difficult,[6, 7, 9] which can mainly be explained by the weaker leaving-group ability of the amine group as compared to the use of sulfonium ylides.…”

Applications of Chiral Three-membered Rings for Total Synthesis: A Review

“…An innovative scaffold for the starting sulfide has been reported by Sarabia et al, based on the use of easily available amino acids Land D-methionines (Scheme 57) [126]. For example, sulfonium salt 143 was readily prepared in four steps and 70% overall yield from L-methionine.…”