Synthesis of 2-Benzazepines from Benzylamines and MBH Adducts Under Rhodium(III) Catalysis via C(sp²)–H Functionalization

Abstract

The rhodium­(III)-catalyzed cross-coupling reaction between commercially available benzylamines and Morita–Baylis–Hillman (MBH) adducts is described. This protocol provides a facile access to various 2-benzazepine derivatives via the C­(sp2)–H activation of N-allylated benzylamines and subsequent intramolecular olefin insertion followed by N-allylation reaction. A range of substrates has been used, and a high level of chemoselectivity as well as functional group tolerance was observed. To gain mechanistic insight of this transformation, DFT calculations were also performed.

Allylic Acetals as Acrolein Oxonium Precursors in Tandem C−H Allylation and [3+2] Dipolar Cycloaddition

“…In these transformations, we observed that the ester functionality on MBH adducts can lower the energy barrier of the migratory insertion step, hence enhancing the catalytic cycle. On the other hand, allyl acetate was inactive under the identical reaction condition, which was supported by DFT calculations . These results indicate that the electron density on olefin moiety is crucial for the success of the reaction.…”

“…Alkenes have been intensively studied for the formation of heterocyclic compounds in C−H functionalization event involving the nucleophilic addition of directing groups to olefinic moieties or the electrophilic addition of directing groups to M−C intermediates. Very recently, our group disclosed the Rh III ‐catalyzed C−H functionalization and in situ annulation reaction using Morita–Baylis–Hillman adducts to afford 2‐benzazepines, bridged benzoxazepines, and 2‐naphthols . In these transformations, we observed that the ester functionality on MBH adducts can lower the energy barrier of the migratory insertion step, hence enhancing the catalytic cycle.…”

Rh(III)-Catalyzed C–H Bond Activation for the Construction of Heterocycles with sp3-Carbon Centers

“…Seven-member heterocyclic scaffolds, especially azepines or their derivatives have attracted considerable attention by virtue of their interesting biological properties. [109,110] Kim's group in 2017 reported another interesting Rh(III)-catalyzed cross-coupling reaction between benzylamines and Morita-Baylis-Hillman (MBH) adducts to build a wide range of 2benzazepine derivatives (Scheme 31) [112]. This transformation has a good chemoselectivity as well as high functional group tolerance.…”

“…between benzylamines and Morita-Baylis-Hillman (MBH) adducts to build a wide range of 2benzazepine derivatives (Scheme 31) [112]. This transformation has a good chemoselectivity as well as high functional group tolerance.…”

“…Recently, emerging transition-metal mediated C-H bond activation provides another convenient way to give access to spirocyclic compounds, in which several groups have reported a In 2018, Chabaud and co-workers ingeniously tethered allylic alcohols into benzamide scaffold to further fulfill a Rh(III)-catalyzed aryl C-H activation/intramolecular Heck-type reaction cascade to access tricyclic azepinones through an intramolecular process (Scheme 32) [113]. Kim's group in 2017 reported another interesting Rh(III)-catalyzed cross-coupling reaction between benzylamines and Morita-Baylis-Hillman (MBH) adducts to build a wide range of 2benzazepine derivatives (Scheme 31) [112]. This transformation has a good chemoselectivity as well as high functional group tolerance.…”