Rapid Synthesis of anti‐1,3‐Diamino‐4‐phenylbutan‐2‐ol Building Blocks via a Three‐Component Oxyhomologation and a Two‐Component Reducing System

Cabua, Maria Chiara

First

Investigation

;He, Xuefeng

Second

;Secci, Francesco

Conceptualization

;Deloisy, Sandrine

Penultimate

Supervision

;Aitken, David J.

Last

Funding Acquisition

2024-01-01

---

Abstract

N1-substituted derivatives of anti-(2R,3S)-1,3-diamino-4-phenyl-butan-2-ol are important building blocks for the synthesis oftherapeutically important molecules. We describe a simpleprotocol that allows transformation of N,N-dibenzyl-L-phenyl-alaninal into such compounds in only two steps. The first step isa fully stereoselective three-component MAC (Masked AcylCyanide) oxyhomologation reaction implicating differentamines to give a panel of ten N,N-dibenzyl-O-tert-butyldime-thylsilyl-protected anti-(2S,3S)-allophenylnorstatin amides. Thesecond step is a carbonyl-activated hydride deprotection/reduction protocol using trimethylsilyl chloride and lithiumaluminium hydride; the one-pot two-component system ismore efficient than the alternative approach of isolating thedeprotected amide intermediate before reduction.