Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

Abstract

SummaryThe formation of alkylidenezinc carbenoids by 1,4-addition/carbozincation of dialkylzincs or alkyl iodides based on zinc atom radical transfer, in the presence of dimethylzinc with β-(propargyloxy)enoates having pendant iodo- and bromoalkynes, is disclosed. Formation of the carbenoid intermediate is fully stereoselective at −30 °C and arises from a formal anti-selective carbozincation reaction. Upon warming, the zinc carbenoid is stereochemically labile and isomerizes to its more stable form.

Trans‐Selective Radical Silylzincation of Ynamides

“…[8,9] Thus, finding a method to achieve the silylmetalation of alkynes in a trans-stereoselective manner is highly relevant. The demonstration that the trans carbozincation [10,11] of alkynes can be achieved by a radical mechanism led us to consider a radical-based silylzincation approach to address this issue.Here we focus on ynamides, because the functionalization of these nitrogen-substituted alkynes through addition reactions across their CC bond is currently attracting attention. [12] A number of protocols was developed for the silylmetalation of ynamides (Scheme 1).…”

“…[8,9] Thus, finding a method to achieve the silylmetalation of alkynes in a trans-stereoselective manner is highly relevant. The demonstration that the trans carbozincation [10,11] of alkynes can be achieved by a radical mechanism led us to consider a radical-based silylzincation approach to address this issue.…”

Stereodivergent Silylzincation of α-Heteroatom-Substituted Alkynes

“…The stereodivergence in these silylzincation reactions is indicative of a mechanistic dichotomy between the two zinc reagents. While the E selectivity observed with (Me 2 PhSi) 2 Zn is consistent with a conventional anionic silicon transfer, the Z selectivity predominantly obtained with [(Me 3 Si) 3 Si] 2 Zn points to an uncommon radical transfer. , …”

“…Thus, both (Me 2 PhSi) 2 Zn and [(Me 3 Si) 3 Si] 2 Zn react with excellent β-selectivity in the absence of any catalyst but with opposite diastereoselectivity . We explain the observed reversal of stereoselectivity with a polar mechanism in the case of (Me 2 PhSi) 2 Zn and a radical-chain mechanism in the case of [(Me 3 Si) 3 Si] 2 Zn. , …”

Exploration of Dimethylzinc‐Mediated Radical Reactions

“…The intramolecular hydrogen‐transfer process, discussed in the last section, would provide a powerful solution for this problem. Since our reports, dimethylzinc has become more and more popular as a radical initiator [63f,89c,95,96] . We believe that the advantages of dimethylzinc are still to be explored.…”