Progress and developments in the turbo Grignard reagent i-PrMgCl·LiCl: a ten-year journey

Abstract

Over the past decade, the effectiveness of i-PrMgCl·LiCl has been constantly highlighted by a number of research groups. Its enhanced nucleophilicity brings prosperity to highly functionalized Grignard reagents, other useful bimetallic (alkali-metal) agents and nucleophilic alkylation products under mild reaction conditions. In this feature article, a comprehensive, systematical and in-depth overview of i-PrMgCl·LiCl is provided in a multidisciplinary idea. It involves the structural and kinetic perspectives of i-PrMgCl·LiCl as well as its unique reactivity and selectivity, with knowledge of the former helping to rationalize trends of the later.

Strain-Release Heteroatom Functionalization: Development, Scope, and Stereospecificity

“…Control reactions with the free amine (no metal, Butov’s dehydroadamantane conditions) gave only traces of product by LC/MS (entries 10, 11). The key breakthrough was achieved when dibenzylamine was treated with Knochel’s turbo Grignard ( i -PrMgCl·LiCl) 38 to give the corresponding “turbo amide” ( 43 , Bn 2 N-MgCl·LiCl); this reagent reacted smoothly with 6 to deliver 24 in 73% yield (entry 22). Perhaps most importantly, the “turbo amide” was completely unreactive with bromobenzene, giving a very clean reaction profile and greatly simplifying purification.…”

Palladium-Catalyzed Cross-Coupling of Monochlorosilanes and Grignard Reagents

“…Alkyl magnesium chloride reagents are known to be highly aggregated in solution, and are often inferior Grignard reagents compared to their heavier halogen congeners. 21 We believe that aggregation may be the reason for the sluggish reactivity observed in this study. Supporting this, addition of substoichiometric TMEDA, which is known to break up RMgCl aggregates, dramatically increased the observed reactivity under the “all chloride” conditions (entry 3).…”

“…Gratifyingly, we found modest reactivity using (DrewPhos) 2 PdI 2 as catalyst, however selectivity was shifted from sec -alkylsilane 1 in favor of the linear al-kylsilane product 2 (Table 1, Entry 1). 20 The use of i PrMgCl·LiCl (the so-called “Turbo Grignard”) 21 and i PrMgBr both improved the yield of the reaction, but the selectivity remained poor (Entries 2–3). Critically, changing the solvent to the less polar Et 2 O maintained the yield while providing complete selectivity in favor of the sec -alkyl product 1 (Entry 5).…”

Photocontrolled Synthesis of n‐Type Conjugated Polymers

“…After precipitation, P1 was obtained in 39 % yield ( M n =25.5 kg mol −1 , Ð=1.61 by THF gel permeation chromatography (GPC) at 40 °C). “Turbo Grignard” reagents of the stoichiometry RMgCl⋅LiCl have been shown to benefit from enhanced reactivity for both small‐molecule coupling and polymerization . The need for superstoichiometric addition of LiCl suggests a further contribution to the reaction medium.…”

“…"Turbo Grignard" reagents of the stoichiometry RMgCl·LiCl have been shown to benefit from enhanced reactivity for both small-molecule coupling and polymerization. [35,36] Then eed for superstoichiometric addition of LiCl suggests afurther contribution to the reaction medium. Them ixed solvent system (toluene/ THF) described by Hayashi and co-workers provided similar results to THF alone (entry 4).…”