N-Heterocyclic Carbene Catalyzed Deoxygenative α-Benzylation of Ketones via Oxidative C(sp 3 )-H Bond Functionalization
Ravi Kant Yadav, Janmejaya Sen, Sandeep Chaudharyintroduction:
In context with C(sp3)–H bond activation reactions, the formation of a, a-disubstituted ketones using a transition-metal-free, eco-friendly and sustainable approach will be of great interest and demand. Noticeably, several reports have been mentioned in the field of catalysis in order to replace the transition-metal catalyst with more eco-friendly organic catalysts. Despite significant progress in recent decades, there has been no report on the arylation of methylene or methylene ketones using NHC as an organocatalyst.
materials and methods:
We report a metal-free, oxidant-free, convenient, mild, and sustainable approach for the synthesis of α-benzylation of methyl ketones (4a-h) and (5a-b) up to 93% yield under the optimized reaction conditions using substituted acetophenones (1a-b and 2a-b) and benzyl alcohol 3a-h as the coupling partner
results:
The protocol is operationally simple and is feasible under mild reaction conditions. The developed protocol is well tolerated towards a diverse functional group. The gram-scale synthesis highlights the versatility of the developed methodology. Also, we have performed various control experiments, including radical scavenger experiment, to gain insights into the mechanism that suggests the possible radical pathway. The reaction proceeds via the dehydrogenation of benzyl alcohol via the SET process to form aldehyde. Then the in-situ aldehyde reacts with methyl ketone to form the chalcone, which receives 2H+ and 2e- from the cation radical to afford the final α-benzylated ketones.
discussion:
After extensive optimization of the reaction condition, particularly, screening of organocatalyst, the reaction of 1a and 3a taken with 20 mol% of catalyst J [1,3-bis(2,4,6 trimethylphenyl)imidazolium chloride] and 1 equivalent of KOtBu in toluene at 120 °C for 18h afforded 93% of 3a, which has been identified as the best optimized reaction conditions.
conclusion:
Herein, we have developed an N-heterocyclic carbene organocatalyzed, highly efficient, transition metal-free, economic protocol for the synthesis of α-benzylation of ketones (4a-h) and (5a-b) up to 93% yield via C(sp3)-H bond activation.