TMPZnOPiv•LiCl: A New Base for the Preparation of Air-Stable Solid Zinc Pivalates of Sensitive Aromatics and Heteroaromatics

Abstract

A wide range of aryl and heteroaryl zinc pivalates bearing sensitive functionalities were prepared by selective metalation using TMPZnOPiv•LiCl, a new hindered zinc amide base. The new zinc reagents are easy-to-handle solids, which maintain their activity almost entirely (>95%) after 4 h of air exposure and smoothly undergo Negishi cross-couplings and reactions with various electrophiles such as Cu(I)-catalyzed acylations and allylations.

Air‐Stable Solid Aryl and Heteroaryl Organozinc Pivalates: Syntheses and Applications in Organic Synthesis

“…Other zincates and related ate bases have also been reported 18. Recently, we prepared a new base by treating TMPMgCl ⋅ LiCl ( 2 ) with Zn(OPiv) 2 ( 1 b , 1.05 equiv) to give the corresponding zinc amide, tentatively written as TMPZnOPiv ⋅ Mg(OPiv)Cl ⋅ LiCl ( 3 ; Scheme ) 5c. This base proved to be compatible with functionalities such as a nitro group, an aldehyde, or sensitive heteroaromatic rings, and gives access to a multitude of new solid organozinc pivalates, which show excellent stability towards air 11…”

“…The air‐stability of such zinc organometallics was substantially superior to organozinc pivalates prepared by magnesium insertion (or exchange) 5b. In the presence of sensitive functionalities such as an aldehyde or a nitro group, the milder zinc amide base TMPZnOPiv⋅Mg(OPiv)Cl ⋅ LiCl5c ( 3 ) may be used for highly selective metalation reactions to give the desired organozinc reagents, which undergo a range of reactions with various electrophiles.…”

Preparation of Solid Polyfunctional Alkynylzinc Pivalates with Enhanced Air and Moisture Stability for Organic Synthesis

“…Preliminary studies have shown that the deprotonation of trimethylsilylacetylene ( 2 a ) with TMPZnOPiv⋅LiCl proceeded smoothly, but produced a solid alkynylzinc reagent ( 1 a ) with moderate air stability (44 % activity after 4 h in air). We speculated that this problematic air and moisture sensitivity was due to the presence of LiCl and designed therefore a new synthesis of TMPZnOPiv ( 3 ) which did not contain LiCl.…”

Solid Organozinc Pivalates: A New Class of Zinc Organometallics with Greatly Enhanced Air- and Moisture-Stability

“…A directed zincation was achieved by using the TMPbase TMPZnCl•Mg(OPiv) 2 •LiCl conveniently abbreviated as TMPZnOPiv•LiCl. This zinc amide base is quite active and well soluble in THF (0.85 M) 20 compared with TMPZnCl•LiCl (ca. 1.4 M).…”

“…Treatment of functionalized benzonitrile 9a with TMPZnOPiv•LiCl at 50 °C for 2 hours produces, after solvent evaporation, solid arylzinc pivalate 10a in 91% yield. 12,20 Sensitive functional groups such as an aldehyde function are well tolerated, and 3-formylbenzothiophene (9b) is readily zincated with TMPZnOPiv•LiCl at 25 °C within 30 minutes, furnishing, after solvent evaporation, heterocyclic zinc pivalate 10b in 89% yield (Scheme 5).…”