Palladium-Catalyzed γ,γ′-Diarylation of Free Alkenyl Amines

Abstract

The direct difunctionalization of alkenes is an effective way to construct multiple C–C bonds in one-pot using a single functional group. The regioselective dicarbofunctionalization of alkenes is therefore an important area of research to rapidly obtain complex organic molecules. Herein, we report a palladium-catalyzed γ,γ′-diarylation of free alkenyl amines through interrupted chain walking for the synthesis of Z-selective alkenyl amines. Notably, while 1,3-dicarbofunctionalization of allyl groups is well precedented, the present disclosure allows 1,3-dicarbofunctionalization of highly substituted allylamines to give highly Z-selective trisubsubstituted olefin products. This cascade reaction operates via an unprotected amine-directed Mizoroki–Heck (MH) pathway featuring a β-hydride elimination to selectively chain walk to furnish a new terminal olefin which then generates the cis-selective alkenyl amines around the sterically crowded allyl moiety. This operationally simple protocol is applicable to a variety of cyclic, branched, and linear secondary and tertiary alkenylamines, and has a broad substrate scope with regard to the arene coupling partner as well. Mechanistic studies have been performed to help elucidate the mechanism, including the presence of a likely unproductive side C–H activation pathway.

Recent Advances in Alkenyl sp2 C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

“…Following this, the same group extended to report the efficient synthesis of Z -selective alkenyl amines by the γ,γ′-diarylation reaction of unprotected β-alkyl allylamines through an interrupted chain walking process (Scheme ). In this case, they found that the choice of silver salt plays a significant role in arylating the less bulkier secondary and tertiary amines. Even the unprotected allyamines could react efficiently in this protocol.…”

Divergent regioselective Heck-type reaction of unactivated alkenes and N-fluoro-sulfonamides

“…= 1:3) meant the possibility of a regioselectivity switch to allylic products. Encouraged by this hypothesis, more nonpolar solvents were tested (entries [18][19], and the r.r. value could be elevated to 1:8 in benzene with a low overall yield of 15% for the coupling products.…”

“…In the past few decades, unremitting efforts have been devoted to this field 11,12 . White et al pioneered a substrate-chelated oxidative Heck reaction of phenylboronic acids and unactivated alkenes tethered with proximal heteroatoms for the regioselective synthesis of vinyl products [13][14][15][16][17][18] . Shortly thereafter, the Sigman group reported a catalyst-controlled β-H elimination process in both oxidative and classic Heck reactions of unactivated alkenes, giving good selectivity for the E-styrenyl products.…”

Catalytic Asymmetric Diarylation of Internal Acyclic Styrenes and Enamides

“…In the meantime, the leverage of the M–H intermediate as the reactive intermediate through the chain-walking strategy has recently been the focus of efforts toward the remote functionalization of alkenes. − Notable examples include the asymmetric Pd-catalyzed relay-Heck reaction, − and the migratory asymmetric hydrofunctionalization of olefins involving an NiH intermediate. − These approaches enable facile access to one distal stereogenic center from the functional group. In stark contrast, the migratory asymmetric dicarbofunctionalization of acyclic internal alkenes has remained underdeveloped. − If realized, the concomitant formation of the incontiguous stereocenters would enable the expedient synthesis of chiral acyclic organic molecules that is challenging for the traditional synthetic routes. At the outset of this project, we envisioned that the judicious choice of alkene bearing a mono-coordinated group would offer the opportunity to control the regio- and diastereoselectivity, while the interception with a wide range of bidentate chiral ligands would result in high enantioselectivity. , To this end, we report the progress on the asymmetric Pd-catalyzed diarylation of internal acyclic alkenes by the reaction of diazonium salts, organoboronic reagents, and two types of easily accessible internal alkenes, allyl carbamates, and enamides (Figure c).…”