Direct Access to Functionalized Azepanes by Cross-Coupling with α-Halo Eneformamides

Abstract

The synthesis of functionalized azepanes was accomplished through the palladium-mediated cross-coupling of α-halo eneformamides with mostly unactivated nucleophiles under mild conditions. Alkenylations proceeded with excellent stereoselectivitiy. In most cases, high yields of the coupling products were obtained.

Recent applications of aziridine ring expansion reactions in heterocyclic synthesis

“…147 The functionalized azepanes have flexible ring structures and this conformational diversity is important for their bioactivity. The structural flexibility of azepanes offers potent inhibition against various enzymes.…”

Palladium-catalysed ligand-free reductive Heck cycloisomerisation of 1,6-en-α-chloro-enamides

“…Ynamides and enamides are versatile functional groups that are finding use as fascinating building blocks for the synthesis of nitrogen-containing compounds. 9 Recently, Sarpong reported intermolecular Heck coupling reactions of bench-stable α-halo eneformamides in DMF or 1,4-dioxane 10 and Tang reported a reduction of the α-halo-enamide to the enamide using Et 3 N as a reductant (Scheme 1). 11 In order to explore the balance of reactivity and stability of α-halo-enamides, we prepared more electrophilic αchloro tosylmides 7a and employed Sarpong's Heck conditions to test the potential intramolecular cyclisation of 7a.…”

Stereocontrolled synthesis of vicinally functionalized piperidines by nucleophilic β-addition of alkyllithiums to α-aryl substituted piperidine enecarbamates

“…This observation highlights the significant reactivity differences in the lithiation chemistry of azacycles of different ring sizes. 21,1b …”