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. 2023 Aug 21;62(34):e202306277.
doi: 10.1002/anie.202306277. Epub 2023 Jul 11.

Synthesis of Quaternary and Tertiary Carbon-Substituted Arenes by Lewis Base Promoted Site-Selective Coupling with Allylic Nucleophiles

Hawa Keita  1 , Simon J Meek  1
Affiliations

Synthesis of Quaternary and Tertiary Carbon-Substituted Arenes by Lewis Base Promoted Site-Selective Coupling with Allylic Nucleophiles

Hawa Keita et al. Angew Chem Int Ed Engl. .

Abstract

A practical method for the preparation of quaternary and tertiary allyl-substituted heteroarenes by site-selective couplings of heteroaryl nitriles and allylic nucleophiles is disclosed. Transformations utilize readily accessible stable reagents, proceed in the presence of a Lewis base activator, and undergo aryl-C(sp3 ) quaternary and tertiary carbon formation with high γ-selectivity (up to >98 : 2 γ : α).

Keywords: Allylation; Arene Coupling; Heterocycle; Organoboron; Quaternary Carbon.

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Conflict of interest statement

Conflict of Interest

The authors declare no conflict of interest.

Figures

Scheme 1.
Scheme 1.
Site-selective allylic nucleophile–arene couplings. (pin=pinacolato)
Scheme 2.
Scheme 2.
Site-selective synthesis of tert-prenyl heteroarenes. [a] Reactions performed under N2 atmosphere. [b] NMR yield and γ:α site selectivity determined by analysis of 1H NMR spectra of crude reactions with hexamethyldisiloxane as internal standard. [c] 3.0 equiv of CsF in DMF. See the supplementary information for details.
Scheme 3.
Scheme 3.
Allylic nucleophile and heteroarene scope. [a] Reactions performed under N2 atmosphere. [b] NMR yield and γ:α site selectivity determined by analysis of 1H NMR spectra of crude reactions with hexamethyldisiloxane as internal standard. [c] 3.0 equiv of CsF in DMF. See the supplementary information for details. See the SI for details.
Scheme 4.
Scheme 4.
Representative coupling utility. [a] Reactions performed under N2 atmosphere. [b] NMR yield and γ:α site selectivity determined by analysis of 1H NMR spectra of crude reactions with hexamethyldisiloxane as internal standard. [c] 3.0 equiv of CsF in DMF. See the supplementary information for details.
Scheme 5.
Scheme 5.
Mechanism experiments. See the supplementary information for details.
See this image and copyright information in PMC

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