Copper-Catalyzed Vinylogous Aerobic Oxidation of Unsaturated Compounds with Air

Abstract

A mild and operationally simple copper-catalyzed vinylogous aerobic oxidation of β,γ- and α,β-unsaturated esters is described. This method features good yields, broad substrate scope, excellent chemo- and regioselectivity, and good functional group tolerance. This method is additionally capable of oxidizing β,γ- and α,β-unsaturated aldehydes, ketones, amides, nitriles, and sulfones. Furthermore, the present catalytic system is suitable for bisvinylogous and trisvinylogous oxidation. Tetramethylguanidine (TMG) was found to be crucial in its role as a base, but we also speculate that it serves as a ligand to copper(II) triflate to produce the active copper(II) catalyst. Mechanistic experiments conducted suggest a plausible reaction pathway via an allylcopper(II) species. Finally, the breadth of scope and power of this methodology are demonstrated through its application to complex natural product substrates.

Computational exploration of copper catalyzed vinylogous aerobic oxidation of unsaturated compounds

“…The copper-assisted deprotonation step is the rate-determining step, where TMG base plays a pivotal role in hydrogen abstraction. This result coincides with the experimental observation that in the absence of TMG www.nature.com/scientificreports/ there is no product generated 45 . Furthermore, our computational results suggest the activation of O 2 molecule proceeds via a six-membered chair-like transition state, which is different from the common end-on or side-on O 2 activation model 7 and accounts for the regioselective γ-carbon activation.…”

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…More recently, a Cu(II)-catalyzed, vinylogous aerobic oxidation of unsaturated esters with air was reported by Newhouse, Yin, et al ( Scheme 195 ). 507 Under the optimized reaction conditions, a mild and operationally simple Cu(OTf) 2 -catalyzed vinylogous aerobic oxidation of β,γ-unsaturated ester 760 and the corresponding α,β-unsaturated congener 762 afforded γ-hydroxy ester derivatives (±)- 761 in good yields (up to 86–92%) as single diastereoisomers ( Scheme 195 , eqs 1 and 2). Furthermore, under similar reaction conditions, bisvinylogous and hypervinylogous oxidations were performed, yielding the corresponding polyunsaturated products (±)- 764 and (±)- 766 with comparable yields and selectivities ( Scheme 195 , eq 3).…”

Chemoselective γ‐Oxidation of β,γ‐Unsaturated Amides with TEMPO

“… [20] TEMPO addition to ketenes was previously reported, including one sole example of γ‐aminoxylation, albeit in low yield [21a] . γ‐Hydroxylation of carbonyls, however not selective to amides, has also been achieved under copper catalysis [21b] . A general method for direct, chemoselective γ‐oxidation of unsaturated amides has, however, not emerged yet.…”

“… [21a] γ‐Hydroxylation of carbonyls, however not selective to amides, has also been achieved under copper catalysis. [21b] A general method for direct, chemoselective γ‐oxidation of unsaturated amides has, however, not emerged yet. Our group has previously studied the interception of keteniminium ions in oxidative contexts beyond the use of N ‐oxides, namely involving the persistent radical TEMPO.…”