Scalable Preparation of the Masked Acyl Cyanide TBS-MAC

oleh: Haley Hinton, Jack Patterson, Jared Hume, Krunal Patel, Julie Pigza

Format: Article
Diterbitkan: MDPI AG 2023-06-01

Deskripsi

This paper describes the three-step synthesis of TBS-MAC, a masked acyl cyanide (MAC) and a versatile one-carbon oxidation state three synthon. We have developed a scalable and detailed synthesis that involves: (1) acetylation of malononitrile to form the sodium enolate, (2) protonation of the enolate to form acetylmalononitrile, and (3) epoxidation of the enol, rearrangement to an unstable alcohol, and TBS-protection to form the title compound. Both the sodium enolate and acetylmalononitrile are bench-stable precursors to the intermediate hydroxymalononitrile, which can be converted to other MAC reagents beyond TBS by varying the protecting group (Ac, MOM, EE, etc.).