Hydroalkylation of Vinylarenes via Transition Metal-Free In-Situ Generation of Benzylic Nucleophiles using Tetramethyldisiloxane and KOtBu

03 October 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Hydrosilanes and Lewis bases are known to promote various reductive defunctionalizations, rearrangements, and silylation reactions, facilitated by enigmatic silicon/Lewis base-derived reactive intermediates. Despite the wide variety of transformations enabled by this reagent combination, no examples of intermolecular C(sp3)–C(sp3) forming reactions have been reported. In this work, we’ve identified 1,1,3,3-tetramethyldisiloxane (TMDSO) and KOtBu as a unique reagent combination capable of generating benzylic nucleophiles in-situ from styrene derivatives, which can subsequently react with alkyl halides to give a new C(sp3)–C(sp3) linkage via formal hydroalkylation. Mechanistic experiments suggest that the reaction proceeds through a key hydrogen atom transfer (HAT) step from a hydrosilane reducing agent to styrene, affording a benzylic radical that undergoes reductive radical polar crossover (RRPC) and subsequent SN2 alkylation.

Keywords

silanes
hydroalkylation
reductive radical polar crossover
reductive functionalization
styrenes
nucleophilic substitution

Supplementary materials

Title
Description
Actions
Title
Supporting Information
Description
Experimental procedures, optimization tables, troubleshooting, characterization of organic molecules, and mechanistic studies
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.