Aerobic Oxidative Dehydrogenation of Ketones to 1,4-Enediones

Abstract

An efficient and unprecedented strategy for the synthesis of 1,4-enediones from saturated ketones has been developed via palladium-catalyzed oxidative dehydrogenation. The protocol employs molecular oxygen as the sole oxidant and represents an atom-and step-economic process. The approach showed broad substrate scope, good functional group tolerance, and complete E-stereoselectivity. The reaction mechanism has been investigated through deuterium-labeling experiments and intermediate experiments.

Desulfonylative Electrocarboxylation with Carbon Dioxide

“…2-Methyl-2-phenylpropanoic Acid (23). 75 Isolated by silica gel chromatography (10% of EtOAc in petroleum ether as the eluent) as a white solid in 92% yield (37.7 mg). 1 H NMR (400 MHz, chloroform-d): δ 7.41 (d, J = 7.5 Hz, 2H), 7.35 (t, J = 7.7 Hz, 2H), 7.27 (t, J = 7.1 Hz, 1H), 1.61 (s, 6H).…”

Pentafluorophenyl Group as Activating Group: Synthesis of α‐Deuterio Carboxylic Acid Derivatives via Et3N Catalyzed H/D Exchange

“…Therefore, methods for introducing deuterium into carboxylic acids or their derivatives will be crucial for developing new deuterated pesticides, drugs and materials. Generally, two strategies can be used for the synthesis of deuterated carboxylic acids [3a–f] . In the first strategy, aldehyde is used as the precursor (Figure 3a) [3a] .…”

“…The second strategy is direct H/D exchange of carboxylic acid (Figure 3b) [3b] . Although more convenient, this method is only applicable to specific carboxylic acids and requires harsh reaction conditions, which always requires the usage of NaH, [3c] n ‐BuLi, [3b] CH 3 ONa [3d] and/or high temperature. Recently, Yu and co‐worker have reported a palladium‐catalyzed H/D exchange reaction of benzilic carboxylic acids substituted with electron withdrawing groups (Figure 3c) [3g] .…”

DBU/O2-Mediated Oxidation of Dienones

“…Only a trace amount of tetrahydronaphthalene-2,6-dione ( 2a ) was observed by oxidation of dienone ( 1a ) using Pearlman’s catalyst (entry 16). Corey’s group has explored this highly selective method for the oxidation of α,β-enones to 1,4-enediones, and very recently, the Wang group reported a highly step and atom economic Pd/Cu combination for accessing 1,4-enediones under aerobic conditions . Therefore, the optimal reaction condition for the preparation of 2,6-dione derivatives ( 2a ) was found to be DBU as a base and molecular O 2 as the oxidant in acetonitrile at the reflux temperature.…”

“…Considering the importance of this method in total synthesis and to explore the generality of this protocol for the synthesis of 2,6-dione derivatives ( 2a ), various dienones ( 1 ) synthesized using known procedures were examined under the optimized reaction conditions (Table ). Trienone ( 1b ) via the allylic oxidation reaction under optimized conditions gave compound 2b in a good yield (78%).…”