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

## TL;DR

This paper presents a two-step method to efficiently synthesize important building blocks used in medicinal chemistry.

## Contribution

A simple, stereoselective two-step protocol for synthesizing anti-1,3-diamino-4-phenylbutan-2-ol derivatives.

## Key findings

- The first step uses a three-component oxyhomologation to produce protected amides.
- A one-pot hydride deprotection and reduction system improves efficiency over traditional methods.
- Ten N,N-dibenzyl-protected derivatives were synthesized in a representative panel.

## Abstract

N
1‐substituted derivatives of anti‐(2R,3S)‐1,3‐diamino‐4‐phenylbutan‐2‐ol are important building blocks for the synthesis of therapeutically important molecules. We describe a simple protocol that allows transformation of N,N‐dibenzyl‐L‐phenylalaninal into such compounds in only two steps. The first step is a fully stereoselective three‐component MAC (Masked Acyl Cyanide) oxyhomologation reaction implicating different amines to give a panel of ten N,N‐dibenzyl‐O‐tert‐butyldimethylsilyl‐protected anti‐(2S,3S)‐allophenylnorstatin amides. The second step is a carbonyl‐activated hydride deprotection/reduction protocol using trimethylsilyl chloride and lithium aluminium hydride; the one‐pot two‐component system is more efficient than the alternative approach of isolating the deprotected amide intermediate before reduction.

N
1‐substituted derivatives of anti‐(2R,3S)‐1,3‐diamino‐4‐phenylbutan‐2‐ol are highly important building blocks in medicinal chemistry. This paper describes a remarkably simple, fully stereoselective, two‐step access to a representative panel of these compounds in N
3‐dibenzyl‐protected form.