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

Abstract

A wide range of air-stable, solid, polyfunctional aryl and heteroarylzinc pivalates were efficiently prepared by either magnesium insertion or Hal/Mg exchange followed by transmetalation with Zn(OPiv)2 (OPiv = pivalate). By reducing the amount of LiCl the air stability could be significantly enhanced compared with previously prepared reagents. An alternative route is directed magnesiation using TMPMgCl⋅LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by transmetalation with Zn(OPiv)2 or, for very sensitive substrates, direct zincation by using TMPZnOPiv. These zinc reagents not only show excellent stability towards air, but they also undergo a broad range of C-C bond-formation reactions, such as allylation and carbocupration reactions, as well as addition to aldehydes and 1,4-addition reactions. Acylation reactions can be performed by using an excess of TMSCl to overcome side reactions of the omnipresent pivalate anion.

Copper‐ and Cobalt‐Catalyzed Syntheses of Thiophene‐Based Tertiary Amines

“…We next involved thiophene‐based and related organozinc chlorides in cobalt‐catalyzed amination reactions. First, arylzinc compounds were prepared by transmetalation of the corresponding arylmagnesium reagents obtained by LiCl‐favored reactions: 2‐thienyl‐ and 2‐benzothienylmagnesium bromides by Grignard reaction ( insertion method A ; Scheme , top), and 2‐thiazolyl‐ and 2‐benzothiazolylmagnesium bromides by bromine/metal exchange ( exchange method B , bottom). The amination step was successfully performed to respectively afford 1c , 2c , 2e , 2f and 4c , 5e , 5f , 5g by using N ‐(benzoyloxy) secondary amines in the presence of CoCl 2 · 2LiCl, a combination that recently proved efficient to functionalize organozincs prepared from other aryl halides , …”

“…General procedure 3 for the preparation of 2‐thienylzinc chloride or 2‐benzothienylzinc chloride (insertion method A) , and subsequent amination …”

Preparation of Solid, Substituted Allylic Zinc Reagents and Their Reactions with Electrophiles

“…Accordingly, the allylic reagents 1 a and 1 b react in THF under very mild conditions (1 h, −78 °C) with 4‐chlorobenzoyl chloride ( 7 a ) and 4‐methoxybenzoyl chloride ( 7 b ) to give the β,γ ‐unsaturated ketones 8 a – c in 78–95 % yield without any trace of the α,β ‐unsaturated isomers. Interestingly, the competitive formation of a mixed anhydride through reaction of the pivalate anion (PivO − ) with the acyl chloride was not observed 9e. Starting from 3‐bromobenzoyl chloride ( 7 c ) or 4‐( tert ‐butyl)benzoyl chloride ( 7 d ), the corresponding β,γ ‐unsaturated ketones 8 d – e were obtained in 68–75 % yield when using the functionalized organozinc pivalate 1 e .…”

Cobalt‐Catalyzed Cross‐Couplings between Alkenyl Acetates and Aryl or Alkenyl Zinc Pivalates

“…With these optimized reaction conditions in hand, we investigated the scope of the cross‐coupling of alkenyl acetates with organozinc pivalates (Table ). All aryl zinc pivalates were prepared from the corresponding aryl bromides by Mg insertion in the presence of LiCl or by Br/Mg exchange using i PrMgCl⋅LiCl, followed by transmetalation with Zn(OPiv) 2 (Table ). ArZnCl⋅Mg(OPiv) 2 ⋅LiCl was abbreviated as ArZnOPiv for the sake of clarity .…”