Stereospecific nucleophilic substitution at tertiary and quaternary stereocentres

Abstract

Nucleophilic substitution reactions have always been considered as one of the most powerful reactions for the creation of carbon-carbon or carbon-heteroatom bonds in organic synthesis. However, stereoselective transformations were restricted to...

Kinetic Resolution of Tertiary Allylic Alcohols: Highly Enantioselective Access to Cyclic Ethers Bearing an α-Tetrasubstituted Stereocenter

“…Several distinct transformations have been developed for such targets, including [3+2] cycloadditions, alkene functionalizations, oxa-Michael reactions, and others . A general method for the direct catalytic substitution of tertiary alcohols through a dehydrative path has remained elusive, despite the enantioselective formation of α-tetrasubstituted oxacycles with water as the sole byproduct. A major difficulty is that unfavorable steric hindrance from the highly congested carbon center usually interferes with the S N 2 reaction, whereas the alternative S N 1 reaction proceeds through a carbocation intermediate, resulting in partial or total loss of stereochemical integrity .…”

α‐Aziridinyl Carbenium Ion Intermediate and Stereoselective Dehydroxylative Diarylation of Aziridin‐2‐yl Carboxaldehyde

“…In recent years, the dehydroxylative cross‐coupling of alcohols has been developed as a method for the direct functionalization of alcohols [3] . In these types of reactions, control of the product stereochemistry is often difficult due to generation of radicals or carbocations as intermediates [4,5] . Although enantiopure alcohols were used as the starting materials, racemic mixtures or enantioenriched compounds with very low enantiomeric excess (ee) values were yielded in the most cases [6] .…”

Asymmetric Nucleophilic Allylation of α-Chloro Glycinate via Squaramide Anion-Abstraction Catalysis: SN1 or SN2 Mechanism, or Both?

“…Nucleophilic substitution reactions are fundamental to organic chemistry. They can occur through either a unimolecular (S N 1) or a bimolecular (S N 2) pathway. − The former involves a stepwise mechanism with a discrete carbenium ion intermediate, while the latter involves a concerted pathway with an associative transition state (TS) in a single step. Although both mechanisms are distinct in nature, most nucleophilic reactions can proceed through either one or both, depending on the experimental conditions and reagents used.…”