Catalytic Transfer Hydrogenation of Arenes and Heteroarenes

Abstract

Transfer hydrogenation reactions are of great interest to reduce diverse molecules under mild reaction conditions. To date, this type of reaction has only been successfully applied to alkenes, alkynes and polarized unsaturated compounds such as ketones, imines, pyridines, etc. The reduction of benzene derivatives by transfer hydrogenation has never been described, which is likely due to the high energy barrier required to dearomatize these compounds. In this context, we have developed a catalytic transfer hydrogenation reaction for the reduction of benzene derivatives and heteroarenes to form complex 3‐dimensional scaffolds bearing various functional groups at room temperature without needing compressed hydrogen gas.

Synthese substituierter Dihydropyridine durch Dearomatisierung von Pyridinen

“…Hauptsächlich wurden alle diese Reaktionen unter strengen inerten Bedingungen durchgeführt und sind durch ihre mühsame Handhabung begrenzt. Kürzlich berichtete unsere Gruppe über eine Rhodium‐katalysierte Transferhydrierung verschiedener (Hetero‐)Aromaten unter Verwendung von Amminboran als Wasserstoffdonor, welches sehr milde reduzierende Bedingungen ermöglichte [9] . Darüber hinaus berichtete die Gruppe von Berke über einen konzertierten Doppelten‐Wasserstoff‐Transfer von Amminboran zur Reduktion von Iminen und Olefinen und demonstrierte damit das katalysatorfreie Reduktionspotential von Aminboran‐Addukten [13] .…”

Amine–Boranes as Transfer Hydrogenation and Hydrogenation Reagents: A Mechanistic Perspective

“…Very recently, Glorius and co‐workers reported the TH of benzene derivatives and heteroarenes using H 3 N⋅BH 3 mediated by [{Rh(cod)(μ‐Cl) 2 }] [83] . Moderate to excellent yields were achieved along with good diastereomeric ratio for numerous substrates (Scheme 36).…”

Substituted Dihydropyridine Synthesis by Dearomatization of Pyridines

“…Therefore, purification was carried out by flash column chromatography over de-activated neutral alumina (see the Supporting Information for further details). A broad range of 3-substituted pyridines could be converted to the corresponding 1,4-DHP-type products in high yields and very good selectivities (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The tolerance of carbonyl groups was shown by the synthesis of DHPs 3 and 4.…”

“…However, this approach is complicated by the necessity of breaking the aromaticity of the substrates, but at the same time preventing the commonly known full reduction to the piperidine (Scheme 1 B). [8,9] In 1972, Fowler described a method in which N-substituted 1,2-DHPs were afforded with low selectivity by reduction of activated pyridines with sodium borohydride (Scheme 1 C). [10] Despite the selectivity issue and a limited substrate scope due to the reactive borohydride species, the Fowler Reduction is a widely used method for accessing N-substituted 1,2-DHPs in very recent studies that exploited the potential of these interesting motifs.…”

“…Recently, our group reported a rhodiumcatalyzed transfer hydrogenation of various (hetero-)arenes utilizing ammonia borane as hydrogen donor resulting in very mild reducing conditions. [9] Moreover, the group of Berke reported a concerted double hydrogen transfer of ammonia borane for the reduction of imines and olefins, demonstrating the catalyst-free reducing potential of amine borane adducts. [13] We envisioned that amine boranes would be suitable mild reducing agents to give access to DHPs when reacted with pyridines (Scheme 1 C).…”