Highly Selective β‐Hydride Elimination in the Pd‐Catalyzed Cross‐Coupling of N‐Tosylhydrazones with Benzyl Bromides

Abstract

In Pd‐catalyzed cross‐coupling reactions between tosylhydrazones and organohalides, the competitive β–H elimination of palladium complex intermediate generated through palladium‐carbene complex's migratory insertion is usually avoided by combining two specific coupling partners, in which only one contains a β‐H. To address this limitation, herein we present cross‐coupling reactions between benzyl bromides and tosylhydrazones derived from benzocyclic ketones. Benzyl‐substituted dihydronaphthalenes and 1H‐indenes can be obtained in up to 88% yields and 25:1 selectivity for the cyclic olefin via this method. DFT studies were performed to elucidate the reaction mechanism. The β‐H elimination process, which follows the migratory insertion of Pd carbene intermediates, favours the abstraction of hydrogen atoms on the cyclic skeletons and results in the observed regioselectivity.

I2/DMSO-Catalyzed Transformation of N-tosylhydrazones to 1,2,3-thiadiazoles

“…Since N-tosylhydrazone 1 can be easily formed from ptoluenesulfonhydrazide and a ketone (Sun et al, 2018;El-Harairy et al, 2019a,b;Li et al, 2019;Liu et al, 2019), we then investigated whether or not the cyclization reaction could be carried out in one-pot fashion directly using a ketone and the hydrazide as the precursors. If it was established, the isolation and purification of the N-tosylhydrazone component can be avoided, thus significantly strengthening the synthetic efficiency.…”

Pd‐Catalyzed Regioselective Olefination of N‐Tosylhydrazones with Benzyl Bromides

“…In 2018, we reported a palladium‐catalyzed selective β ‐H elimination of benzocyclic ketone N ‐tosylhydrazones and benzyl bromide (Scheme a) . The results showed that the elimination of β ‐H mainly occurred in the aliphatic ring, and the internal olefin products were mainly generated.…”

Recent Advances in Transition‐Metal‐Catalyzed Reactions of N‐Tosylhydrazones

“…A 1:1 ratio of the substrates allows for a molecule economic strategy and was found to proceed more efficiently in nonpolar solvents, such as toluene, than in polar solvents. Later, the selectivity of β‐hydride elimination for the reaction of benzyl halides with tetralone derived tosylhydrazones was studied, showing preferences to the formation of cyclic alkenes [19] …”

“…Later, the selectivity of βhydride elimination for the reaction of benzyl halides with tetralone derived tosylhydrazones was studied, showing preferences to the formation of cyclic alkenes. [19] In 2009, Bret Tréguier et al reported the synthesis of 1,1-diarylethylenes via palladium-catalyzed arylation of N-tosylhydrazones with aryl triflates to provide molecules related to isocombretastatin A-4 (isoCA-4) (Scheme 8). [20] These molecules show remarkable anticancer activities and potential as antimitotic agents, as well as the ability to selectively damage tumor neovascalture.…”