Recent Advances in Enantioselective Desymmetrizations of Prochiral Oxetanes

Abstract Strain relief of oxetanes offers a plethora of opportunities for the synthesis of chiral alcohols and ethers. In this context, enantioselective desymmetrization has been identified as a powerful tool to construct molecular complexity and this has led to the development of elegant strategies on the basis of transition metal, Lewis acid, and Brønsted acid catalysis. This review highlights recent examples that harness the inherent reactivity of prochiral oxetanes and offers an outlook on the immense possibilities for synthetic application.

Desymmetrization of Prochiral Cyclobutanones via Nitrogen Insertion: A Concise Route to Chiral γ‐Lactams

Abstract Asymmetric access to γ‐lactams is achieved via a cyclobutanone ring expansion using widely available (1S,2R)‐1‐amino‐2‐indanol for chiral induction. Mechanistic analysis of the key N,O‐ketal rearrangement reveals a Curtin–Hammett scenario, which enables a downstream stereoinduction (up to 88:12 dr) and is corroborated by spectroscopic, crystallographic, and computational studies. In combination with an easy deprotection protocol, this operationally simple sequence allows the synthesis of a range of optically pure γ‐lactams, including those bearing all‐carbon quaternary stereocenters. In addition, the formal synthesis of drug molecules baclofen, brivaracetam, and pregabalin further …

Desymmetrisierung von prochiralen Cyclobutanonen via Stickstoffinsertion: Ein einfacher Zugang zu chiralen γ‐Lactamen

CCDC 2051971: Experimental Crystal Structure Determination

Related Article: Jan Sietmann, Mike Ong, Christian Mück-Lichtenfeld, Constantin G. Daniliuc, Johannes M. Wiest|2021|Angew.Chem.,Int.Ed.|60|9719|doi:10.1002/anie.202100642

CCDC 2051973: Experimental Crystal Structure Determination

Related Article: Jan Sietmann, Mike Ong, Christian Mück-Lichtenfeld, Constantin G. Daniliuc, Johannes M. Wiest|2021|Angew.Chem.,Int.Ed.|60|9719|doi:10.1002/anie.202100642

CCDC 2051972: Experimental Crystal Structure Determination

Related Article: Jan Sietmann, Mike Ong, Christian Mück-Lichtenfeld, Constantin G. Daniliuc, Johannes M. Wiest|2021|Angew.Chem.,Int.Ed.|60|9719|doi:10.1002/anie.202100642

CCDC 2051970: Experimental Crystal Structure Determination

Related Article: Jan Sietmann, Mike Ong, Christian Mück-Lichtenfeld, Constantin G. Daniliuc, Johannes M. Wiest|2021|Angew.Chem.,Int.Ed.|60|9719|doi:10.1002/anie.202100642