Selective C(sp³)−N Bond Cleavage of N,N‐Dialkyl Tertiary Amines with the Loss of a Large Alkyl Group via an S_N1 Pathway

Abstract

Polar disconnection of the C(sp3)−N bond of N,N‐dialkyl‐substituted tertiary amines via ammonium species conventionally favored the loss of the smaller alkyl group by an SN2 displacement, while selective C(sp3)−N bond cleavage by cutting off the larger alkyl group is still underdeveloped. Herein, we present a novel Pd0‐catalyzed [2+2+1] annulation, proceeding through an alkyne‐directed palladacycle formation and consecutive diamination with a tertiary hydroxylamine by cleaving its N−O bond and one C(sp3)−N bond, for the rapid assembly of tricyclic indoles in a single‐step transformation. Noteworthy, experimental results indicated that large tert‐butyl and benzyl groups were selectively cleaved via an SN1 pathway, in the presence of a smaller alkyl group (Me, Et, iPr). Under the guidance of this new finding, tricyclic indoles bearing a removable alkyl group could be exclusively obtained by using a (α‐methyl)benzyl/benzyl or tert‐butyl/2‐(methoxycarbonyl)ethyl mixed amino source.

RhodiumIII-catalyzed remote difunctionalization of arenes assisted by a relay directing group

“… 16 The same strategy was extended to alkyne-tethered arenes by the groups of Luan and García-López. 17 Intriguingly, analogous intramolecular annulations have been realized by using meta -olefin-tethered arenes via chelation-assisted C–H activation ( Scheme 2b ). 18 However, this reaction system is limited to the arenes with an olefin unit tethered at the meta - or ortho -position.…”