Characterization and Utilization of the Elusive α,β-Unsaturated N-Tosyliminium: the Synthesis of Highly Functionalizable Skipped Halo Enynes

Abstract

A formal haloalkynylation of allenamides has been described for the synthesis of highly stereo- and regioselective skipped halo enynes. Exclusive γ-regioselectivity is achieved through the intermediacy of a conjugated N-tosyliminium intermediatedirect evidence for the formation of which was validated by NMR and HRMS. Quantum mechanical computations reveal that the reactive intermediate geometry is key to controlling the 1,2- or 1,4-regioselectivity of alkyne interception. Divergent access to elusive unsaturated systems has also been reported.

Chemoselective Coupling of π‐Systems to Access Metallated 1,4‐ or 1,5‐Skipped Dienes in Multicomponent Reactions

“…Considering the above successful attempt and in the context of utilizing allenamides for the stereoselective synthesis of unsaturated carbon skeletons, [4,38] we examined the feasibility of a multicomponent reaction in a more appropriate context [4b] . Furthermore, the mechanistic studies prompted us to investigate the synthesis of bimetallic skipped dienes by addressing the following key questions.…”

Construction of C–N and C–O bonds based on N-allenamide functionalization

“…In 2021, Park et al 32 cleverly used this mode of activation of terminal N -allenamide 107 to obtain N , O -aminals 109 after addition of an alcohol to the N -acyliminium intermediates formed. Addition of in situ generated alkynylzinc species to the allylic halo-ethers 108 provided halogenated yne-enamides 109 in good yields.…”

“…A broad application of this transition-metal-free functionalization of N-allenamides has been nicely summarized by Li, Zhao and co-authors (Scheme 22). 3 In 2021, Park et al 32 cleverly used this mode of activation of terminal N-allenamide 107 to obtain N, O-aminals 109 after addition of an alcohol to the N-acyliminium intermediates formed. Addition of in situ generated alkynylzinc species to the allylic halo-ethers 108 provided halogenated yne-enamides 109 in good yields.…”

General Hydroamination of Allenamides: Mechanistic Insights with an Acetate Adduct and 1,1,1,3,3,3-Hexafluoro-2-propanol

“…Allenamides, a class of 1,2-dienes, have proven to be very valuable precursors for the development of various intriguing transformations since their discovery in 1967. , The interception of nucleophiles centered around C and O from an iminium intermediate has been extensively studied through metal-free electrophilic activation using H + electrophiles, while for nucleophiles centered around N, halonium activators (X + ) are used instead (Scheme A) . Therefore, we were intrigued about the viability of using less-studied N-nucleophiles using a H + electrophile.…”

“…Although there was a minor divergence in regioselectivity for secondary heteroaryl amines 2aH and 2aI , γ-selectivity was still dominant, and the regioisomeric ratios were 89:11 and 86:14, respectively. These findings show that this acetate-assisted amination is unidirectional in terms of the N-centered nucleophile (predominant γ-regioselectivity) and complements the iodonium-induced amination process . Moreover, this coupling showed similar regioselectivity for aliphatic amines featuring phenyl, strained, and bridged cycles and a long carbon chain connected directly to the NH 2 group ( 3aJ – aM ) (Scheme C).…”