Nucleophilic Substitution at Quaternary Carbon Stereocenters

Abstract

Cyclopropyl carbinol derivatives undergo a regio- and stereoselective nucleophilic substitution at the quaternary carbon center, with pure inversion of configuration, to provide the acyclic products as a single diastereomer. The selectivity of the substitution is attributed to the existence of a cyclobutonium species, reacting at the most substituted carbon center. Diastereomerically pure and enantiomerically enriched tertiary alkyl bromide, chloride, ester, and fluoride could therefore be easily prepared in only three catalystic steps from commercially available alkynes.

Pentanidium-Catalyzed Direct Assembly of Vicinal All-Carbon Quaternary Stereocenters through C(sp 3 )–C(sp 3 ) Bond Formation

“…Recent advances include dearomatization addition of -naphthols on 3-bromooxindoles, 18 Claisen rearrangement of -unsaturated carbonyl compounds, 19 dialkylation of bisoxindoles, 20 phosphine-catalyzed cyclization of allenes 21 and a nucleophilic substitution at a quaternary carbon center with concomitant opening of a cyclopropane ring. 22,23 On the other hand, direct radical coupling of two C(sp 3 ) centers is a promising possibility as it can overcome steric hindrance; but currently it is limited to a narrow substrates scope such as bisoxindoles and chiral auxiliaries need to be deployed if enantioenriched compounds are required (Figure 1b). [24][25][26][27] Thus far, there are no successful reports to prepare vicinal all-carbon quaternary stereocenters through a catalytic asymmetric coupling of two tertiary C(sp 3 ) centers.…”

Construction of Carbon‐Fluorine Bonds via Copper‐Catalyzed/‐Mediated Fluorination Reactions

“…In 2020, Marek and coworker reported direct intermolecular nucleophilic displacement on cyclopropyl carbinol derivatives as a general method to prepare acyclic molecular backbones (Scheme 41). [56] Cyclopropyl carbinol derivatives undergo a regio-and stereoselective nucleophilic substitution at the quaternary carbon center, with pure inversion of configuration, to provide the acyclic tertiary alkyl fluorine species as a single diastereomer. The use of readily available HBF 4 aqueous solution as fluorine source makes this transformation more attractive.…”

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.…”