Divergent Reactivity of α,α-Disubstituted Alkenyl Hydrazones: Bench Stable Cyclopropylcarbinyl Equivalents

Abstract

Herein we report the divergent reactivity of 2,2-dialkyl-3-(E)-alkenyl N-tosylhydrazones using Pd-catalyzed crosscoupling conditions, which enable the Z-selective synthesis of 3-aryl-1,4-dienes and gem-dialkyl vinylcyclopropanes. We found that the dialkylbiaryl phosphine ligand SPhos was the optimal ligand for this transformation producing skipped dienes in up to 83% isolated yield. The ratio of skipped diene to vinylcyclopropane is dependent on both the structure of the α,α-disubstituted hydrazones and the aryl halide partner. Using sterically encumbered aryl bromides provided the trans-cyclopropane products selectively in up to 69% yield. The reaction is stereospecific and stereoselective and occurs alongside a competing 1,2-alkenyl group migration pathway.

Origins of Stereospecificity and Divergent Reactivity of Pd-Catalyzed Cross Coupling with α,α-Disubstituted Alkenyl Hydrazones

“…They proposed a view that the stereospecificity of the reactions and the inversion of olefin geometry observed in the skipped diene products are in accord with a syn-β-C elimination elementary step. 11 Our calculated results identify that the syn-β-C elimination is a key step in determining stereoselective transition from E to Z configuration in the skipped diene product. We compared the optimized geometries of the syn-β-C elimination step.…”

“…The oxidative addition is identified as the rate-determining step of the reactions, and the energy barrier is 17.8 kcal/mol. Wilkerson-Hill and co-workers found that using E -hydrazones as stereochemical probes, the formation of the Z -skipped diene product was observed. Conversely, using Z -hydrazones produced the isomeric E -skipped diene.…”

Efficient Synthesis of Orphaned Cyclopropanes Using Sulfones as Carbene Equivalents

“…11 Additionally, diazoalkane starting materials may be toxic, explosive, 12 and not easily obtained through Regitz diazo transfer reactions. 13,14 Thus, these aliphatic cyclopropanes that arise from the transfer of As a part of a research program focused on the efficient construction of orphaned cyclopropanes, 17 we sought to develop a new general platform to transfer unstabilized carbene units to unactivated alkenes. We were drawn to a 1996 report by Julia and co-workers 18 who reported that αlithiated sulfones transfer dialkylcarbene groups to styrenes and other unactivated olefins using Ni(0) catalysis.…”

“…As a part of a research program focused on the efficient construction of orphaned cyclopropanes, we sought to develop a new general platform to transfer unstabilized carbene units to unactivated alkenes. We were drawn to a 1996 report by Julia and co-workers who reported that α-lithiated sulfones transfer dialkylcarbene groups to styrenes and other unactivated olefins using Ni(0) catalysis.…”

Palladium/GF-Phos-catalyzed asymmetric carbenylative amination to access chiral pyrrolidines and piperidines

“…2 Among them, transition-metal-catalyzed cross-coupling is one of the powerful protocols for C–X or CC bond formation in organic synthesis involving versatile intermediates, of which in situ generation of diazo compounds and carbene migratory insertion are considered key steps. 3–5 Over the past decades, considerable progress has been made in the asymmetric cross-coupling reactions of N -tosylhydrazones with various coupling partners, including cyclobutanols, terminal alkynes, silacyclobutanes and so on. 4 Relatively, only a few examples focus on the cross-coupling reactions of aryl halides with N -tosylhydrazones involving benzyl metal intermediates [Scheme 1A, eqn.…”