Cine Substitution with Arylzinc Reagents: Scope and Mechanistic Studies

Abstract

The unexpected ability of arylzinc reagents bearing electron-donating substituents to react in a Friedel-Crafts fashion (cine) with electrophiles like perpivaloylated glucoside bromide and benzhydryl bromides in competition with organometallic coupling (ipso) is shown. The stereoelectronic factors required to promote the cine reactivity versus the classical ipso, and the mechanism of this alternative pathway, have been investigated. The Wheland intermediate is deprotonated intramolecularly in a 1,2-shift but also in a longer-range shift, leaving in this case the C-Zn untouched. In the latter case, it is possible to take advantage of this result for further functionalization.

A Zinc Catalyzed C(sp3)−C(sp2) Suzuki–Miyaura Cross‐Coupling Reaction Mediated by Aryl‐Zincates

“…Bromodiphenylmethane and methylallyl bromide were also effectively cross‐coupled, however, octylbromide and cycloheptylbromide were not amenable. The formation of 3 o was highly selective (>95 %) with minimal products from cine ‐ or tele ‐substitution observed, indicating that an organometallic ipso ‐coupling process dominates 10g. The observed scope is consistent with an S N 2 mechanism, and the minor amounts of homocoupling observed (<5 %) is attributed to a zinc‐free reaction based on Table 1 entry 6.…”

cine- and tele-Substitution reactions: review of work from 2002-2016

“…Three possible mechanisms of cyclization of a radical derived from e.g., ortho-iodoanilides in the presence of samarium(II) iodide are shown in Scheme 23. Very recently, a paper has been published 31 proving that arylzinc reagents bearing electron-donating substituents were able to undergo cine-substitution with certain electrophiles such as perpivaloylated glucoside bromide or benzohydryl bromide under the conditions where stereoelectronic factors promoted cine-versus ipso-substitution (Scheme 29). A mechanism of the substitution was studied and proposed.…”

Glycosyl Cross-Coupling of Anomeric Nucleophiles: Scope, Mechanism, and Applications in the Synthesis of Aryl C-Glycosides

“…Due to the unique position of C -aryl glycosides as privileged glycomimetics, various methods have been described to stereoselectively introduce aryl groups into the anomeric position. 17–22 The most common approaches focus on (i) nucleophilic addition of an organometallic reagent (e.g., organozinc) 23,24 to anomeric halides catalyzed by Ni, 25–28 Co, Pd, and Fe 29 complexes, (ii) addition of a nucleophile to a lactone followed by reduction of the resultant acetal, and (iii) Friedel‒Crafts-type alkylation of electron-rich arenes or direct phenol O -glycosylation followed by a stereoselective O→C rearrangement. 30,31 In the context of C(sp 2 )−C(sp 2 ) cross-couplings, reactions of glycals in the form of a C1-nucleophile 32 or a C1-electrophile 33–35 have been described.…”