Chromium-Promoted Dearomative (Deutero)Hydrocyanoalkylation of (Hetero)Arenes Using Simple Alkylnitriles

Abstract

Herein, a general strategy for the regioselective dearomative 1,2-hydrocyanoalkylation of chromium-bound (hetero)arenes with simple alkylnitriles as pronucleophiles was disclosed, providing rapid access to 1,3-cyclohexadienes possessing useful alkylnitrile groups. The versatility of this methodology further enabled a selective dearomative deuteration reaction. Finally, synthetic applications of the method in the formal synthesis of natural products, including erysotramidine, demethoxyerythratidinone, and morphine, were demonstrated.

Key words

chromium - dearomatization - hydrocyanoalkylation - deuteration - alkylnitrile - cyclohexadiene

Publication History

Received: 21 August 2023

Accepted after revision: 02 October 2023

Accepted Manuscript online:
02 October 2023

Article published online:
06 November 2023

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• 15 Typical Procedure for the Dearomative Hydrocyanoalkylation Under N₂ atmosphere, t-BuOK (0.90 mmol, 3.0 equiv.) was added to the solution of (η⁶-1,4-dimethoxybenzene)Cr(CO)₃ (0.30 mmol, 1.0 equiv.) in CH₃CN (1.5 mL) and THF (1.5 mL) at –45 °C. After stirring for 4 h, the reaction was quenched with CF₃CO₂H (1.5 mmol, 5.0 equiv.) and stirred for another 1 h. The mixture was concentrated and purified by preparative TLC using PE/EtOAc (10: 1) as the eluent to give a pale yellow liquid 8; 48.3 mg, 90% yield. ¹H NMR (500 MHz, CDCl₃, connectivities were confirmed by gCOSY experiments): δ = 4.93 (d, J = 6.5 Hz, 1 H), 4.85 (dd, J = 7.0, 1.5 Hz, 1 H), 3.55 (d, J = 2.0 Hz, 6 H), 2.74–2.68 (m, 1 H), 2.68–2.63 (m, 1 H), 2.52 (dd, J = 16.5, 5.0 Hz, 1 H), 2.46 (dd, J = 16.5, 8.5 Hz, 1 H), 2.34–2.25 (m, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 151.7, 150.4, 118.7, 92.8, 90.8, 55.1, 54.9, 35.4, 32.5, 19.2. HRMS (APCI): m/z calcd [C₁₀H₁₃NO₂ + H]⁺: 180.1019; found: 180.1018.