A general, enantioselective synthesis of N-alkyl terminal aziridines and C2-functionalized azetidines via organocatalysis

Abstract

A short, high-yielding protocol involving the enantioselective α-chlorination of aldehydes has been developed for the enantioselective synthesis of C2-functionalized aziridines and N-alkyl terminal azetidines from a common intermediate. This methodology allows for the rapid preparation of functionalized aziridines in 50–73% overall yields and 88–94% ee, and azetidines in 22–32% overall yields and 84–92% ee. Moreover, we developed a scalable and cost-effective route to the key organocatalyst (54% overall yield, >95% dr).

Sulphide as a leaving group: highly stereoselective bromination of alkyl phenyl sulphides

“…Performing the bromination on easily accessible β-sulphido nitriles 1q and 1r gave rise to the corresponding β-bromonitriles in fair to good yields. Our method provides a direct and simple route to these novel and potentially versatile compounds,23 especially when considering that the only direct literature-known method relies on the mostly low-yielding halodehydration of the corresponding alcohol precursors 24…”

Nitrile Containing Bisphosphonates: Easy Synthesis through Metal Catalyzed Michael Addition

“…The importance of the nitrile group in the side chain of the BP opens the way to the possibility to reduce this moiety to the corresponding amino group, that could further react to give substituted N‐BPs. Several examples of cyano group reduction are reported in the literature using different reducing agents such as hydrogen, sodium borohydride, lithium aluminum hydride, or others . Reduction attempts and functionalization of nitrile group will be the subject of future studies in order to obtain a new class of γ ‐amino BPs as potential new N‐BPs.…”

Recent advances in synthetic facets of immensely reactive azetidines

“…Lindsley and co-workers 19 have devised an enantioselective synthesis of C2-functionalized azetidines from b-chloroalcohol. The methodology involved the initial activation of b-chloro alcohol 57 as triate with subsequent displacement of triate ion with cyanide in presence of 18-crown-6 to afford b-chloronitrile 58.…”