# Stereospecific Radical Bromination of β‐Aryl Alcohols with Thiourea Additives Through A Serendipitous Discovery of A 1,2‐Aryl Migration

## TL;DR

A new bromination method was discovered that preserves the stereochemistry of β-aryl alcohols, thanks to a surprising phenyl group migration.

## Contribution

A novel stereospecific bromination pathway was identified through a serendipitous 1,2-aryl migration mechanism.

## Key findings

- Bromination of chiral secondary alcohols retained stereochemistry instead of producing racemates.
- A 1,2-phenyl migration was observed during bromination, forming a spiro radical intermediate.
- The reaction works under mild conditions for a range of β-aryl alcohols.

## Abstract

The development of new protocols for stereospecific and stereoselective halogenation transformations by mild reaction conditions is a highly desirable research target for the chemical and pharmaceutical industries. Following the straightforward methodology for directly transforming a wide scope of alcohols to alkyl bromides and chlorides using substoichiometric amounts of thioureas and N‐halo succinimides (NXS) as a halogen source in a single step, we noticed that in apolar solvents bromination of chiral secondary alcohols did not produce the expected racemates. In this study, the stereochemical aspects of the bromination reaction were examined. Surprisingly, bromination of (±)‐threo‐ or (±)‐erythro‐3‐phenyl‐2‐butanols revealed a single diastereomeric brominated product with retention of configuration. The scope of these reactions was expanded on several β‐aryl alcohols. During these studies, an unexpected stereospecific 1,2‐migration of the phenyl group was shown to take place. The proposed mechanism of the 1,2‐phenyl migration involves the formation of a spiro[2,5]octadienyl radical, which is then attacked by a bromide radical at any of the two cyclopropyl positions anti to the phenyl position, leading to products that retain the stereoisomeric configuration of the starting material.

In this study, the bromination of diastereomeric β‐aryl alcohols using the N‐bromo‐succinimide (NBS) and thiourea protocol provides a novel pathway to a direct fully stereoretentive bromination of β‐aryl alcohols under very mild conditions.