# The Development of Stereoselective Substrate and Reagent-Controlled Lithiation–Borylation Chemistry

## TL;DR

This paper introduces a new method for creating allylic alcohols in a stereoselective way using chiral polyketide fragments.

## Contribution

A novel stereoselective lithiation–borylation protocol using chiral polyketide fragments without sparteine.

## Key findings

- Chiral polyketide fragments enable high-yield and diastereoselective Hoppe–Matteson–Aggarwal rearrangements.
- Steric and electronic effects strongly influence stereochemical outcomes.
- Guidance flowcharts were developed using conformational analysis and a Felkin-like model.

## Abstract

Allylic alcohols are a privileged motif in polyketide-based
natural
product synthesis, and new methods that access them in a stereoselective
fashion are highly sought after. Toward this goal, we found that the
use of chiral polyketide fragments allows for performing the Hoppe–Matteson–Aggarwal
rearrangement in the absence of sparteine with high yields and diastereoselectivities,
rendering this protocol a highly valuable alternative to existing
methods. Various stereodyads and -triads bearing different protecting
and directing groups were investigated to determine their substrate
induction. The mostly strong inherent induction was attributed to
either steric or a combination of steric and electronic effects. The
stereochemical outcome could be explained by (DFT-based) conformational
analysis and a Felkin-like model, allowing guidance flowcharts to
be created for the substrate- and reagent-controlled lithiation–borylation
chemistry.