Ir-Catalyzed Remote Functionalization by the Combination of Deconjugative Chain-Walking and C–H Activation Using a Transient Directing Group

Abstract

An Ir-catalyzed reaction of N-benzylideneanilines with functionalized alkenes such as α,β-unsaturated esters gave ortho-substituted benzaldehyde derivatives with a functional group at the remote position after acidic treatment. The present transformation involves deconjugative long-range isomerization (chain-walking) up to 11 times and C−H activation using an imino group as a transient directing group.

Nickel-catalyzed tandem isomerization/anti-Markovnikov hydroarylation of unactivated internal alkenes with heteroarenes

“…8 Very recently, Shibata and co-workers have extended the aromatic substrate to N -benzylideneanilines for the formation of linear alkyl-substituted benzaldehyde (Scheme 1c). 9 In contrast to the well-developed single hydroarylation of α-alkenes, the tandem transformation with internal alkenes can generate a new C sp 2 –C sp 3 bond at an initially inert C sp 3 −H bond, thus providing an attractive means of remote C sp 3 −H bond functionalization. 10 Despite these remarkable contributions, transition metal-catalyzed tandem isomerization/ anti -Markovnikov hydroarylation of unactivated internal alkenes with heteroarenes for the preparation of linear alkylheteroarenes has not been reported to date.…”

Iridium-Catalyzed Migratory Terminal C(sp3)–H Amidation of Heteroatom-Substituted Internal Alkenes via Olefin Chain Walking

“…When DMF-d 7 was used as the reaction solvent, amidation (3) took place without deuteration (Scheme 4B), indicating that DMF did not serve as the hydride source. However, when D 2 O was employed as an additive in lieu of H 2 O, deuterium incorporation was also observed mainly at the α-carbon to the OTIPS group (Scheme 4C), suggesting that water may undergo a hydride exchange with the Ir−H species, 42,47,91 which is in situ generated from a reaction of [Cp*IrCl 2 ] 2 with HBpin. 92 In addition, when deuterated substrates 65 and O-silyl enol 1 were used together in a crossover reaction, no deuterium was incorporated in the amidated product 3 (Scheme 4D).…”

“…38 Computational Studies on Terminal-Selective Amidation. With the above experimental mechanistic studies and literature precedents, 47,54,91 we additionally explored the plausible mechanism of the current terminal-selective amidation using density functional theory (DFT) calculations (Figure 1). Given that a hydride species A [Cp*Ir(Cl)(H)] is postulated to be generated at the beginning from the iridium precursor and hydride sources, 92,95,96 Gibbs energies in the chain walking process are summarized in Figure 1A.…”

Ir-Catalyzed Distal Branch-Selective Hydroarylation of Unactivated Internal Alkenes with Benzanilides via C–H Activation along with Consecutive Isomerization

“…The hydridoiridium intermediate triggered deconjugative isomerization of the double bond, giving the terminal alkene. Next, anti-Markovnikov addition forged linear addition products selectively . To the best of our knowledge, the synergistic strategy of C–H activation and consecutive isomerization to give a Markovnikov product has not yet been reported (Scheme C). , As an extension of this study, and due to our continued interest in cationic iridium-catalyzed C–H activation reactions, ,, we further elaborated this synergistic strategy of C–H activation and consecutive isomerization.…”

“…We re-evaluated different directing groups and found that a carbamoyl directing group can also trigger consecutive isomerization. The reaction conditions were the same as those in the previous study, and the starting material was replaced by benzanilide ( 1a ). A mixture of isomers can be generated, including the isomerized product with a branched isomer 3 and a linear isomer 3′ and the nonisomerized product 3′′ .…”