Guerbet-type β-alkylation of secondary alcohols catalyzed by chromium chloride and its corresponding NNN pincer complex

Abstract

The β-alkylation of secondary alcohols has been successfully accomplished using earth abundant, inexpensive and environmentally benign 3d transition metal chromium salt CrCl₃ and its corresponding pincer-Cr complex, (^Ph2NNN)CrCl₃ (0.005 mol%), at 140 °C in air under conventional (3 h) and microwave heating conditions (ca. 75 W for 1.5 h) in the presence of NaO^tBu (5 mol%). Microwave conditions provided better results (90% yield and 18 000 TON at 12 000 TOh⁻¹) in comparison to conventional heating (84% yield and 16 800 TON at 5600 TOh⁻¹). While CrCl₃ (0.005 mol%) afforded 76% yield (15 200 TON at 10 133 TOh⁻¹) of the β-alkylated product under microwave conditions in the presence of 5 mol% NaO^tBu, the corresponding pincer-Cr complex (^Ph2NNN)CrCl₃ (0.005 mol%) resulted in 90% yield (18 000 TON at 12 000 TOh⁻¹) of the β-alkylated product under similar conditions. EPR studies suggest the involvement of chromium(II) active species when either CrCl₃ or its corresponding NNN pincer is used. HRMS analysis, hot-filtration and mercury-drop test provided conclusive evidence for the homogeneous and well-defined molecular nature of the reaction mixture. Apparently, insertion of the α-alkylated ketone into the Cr–H bond is the RDS based on inferences drawn from deuterium labelling studies that demonstrate a KIE of 7.33 and HRMS analysis which provide vital information on the resting-state of the reaction.