Access to Unexplored 3D Chemical Space: cis‐Selective Arene Hydrogenation for the Synthesis of Saturated Cyclic Boronic Acids

Abstract

A new class of saturated boron-incorporated cyclic molecules has been synthesized employing an arene-hydrogenation methodology. cis-Selective hydrogenation of easily accessible, and biologically important molecules comprising benzoxaborole, benzoxaborinin, and benzoxaboripin derivatives is reported. Among the various catalysts tested, rhodium cyclic(alkyl)-(amino)carbene [Rh-CAAC] (1) pre-catalyst revealed the best hydrogenation activity confirming turnover number up to 1400 with good to high diastereoselectivity. A broad range of functional groups was tolerated including sensitive substituents such as À F, À CF 3 , and À silyl groups. The utility of the synthesized products was demonstrated by the recognition of diols and sugars under physiological conditions. These motifs can have a substantial importance in medicinal chemistry as they possess a three-dimensional structure, are highly stable, soluble in water, form hydrogen bonds, and interact with diols and sugars.

cis-Selective Hydrogenation of Aryl Germanes: A Direct Approach to Access Saturated Carbo- and Heterocyclic Germanes

“…Herein, we describe the first comprehensive study for the direct preparation of diastereoselective saturated carbo-cyclic germanes including the unprecedented preparation of valuable saturated heterocyclic germanes via the additive-free hydrogenation of aryl germanes. Previously, the groups of Zeng et al, , Bullock et al, , Andersson et al, our group, ,− ,− and others − have reported novel catalytic arene hydrogenation reactions using rhodium and ruthenium metal-based catalytic systems. Intrigued by these reports, we examined the hydrogenation of aryl germanes employing various molecular complexes and heterogeneous metal species as catalysts.…”

“…Chemoselective reduction of one aromatic ring is one of the most challenging aspects in arene hydrogenation and can be a vital tool for post-functionalization. Acquiring the knowledge from the obtained experimental results and previous literature reports, ,, we envisaged that the hydrogenation of aryl germanes is difficult in comparison to other aromatic rings. Based on this hypothesis, we also investigated selective one-ring hydrogenation.…”

“…The efficient and active protocols to access the novel 3D chemical space are vital within the field of applied sciences. Their installation is essential for the discovery of unprecedented organic frameworks as per their applications in the field of drug discovery, − life sciences, − and agrochemicals. , Owing to the huge potential chemical space as such, a significant interest is present in the chemical community to develop novel methodologies that allow the synthesis of diverse 3D chemical compounds via modular approaches from readily accessible flat building blocks. Organogermanium compounds are versatile intermediates in organic synthesis as they are non-toxic and hydrophobic with the manifestation of biological activities (Scheme , entry a). − These compounds are subjected to medicinal applications − revealing antitumor reactivity , and possess a vital role to understand the pharmacology of plants. , They also represent a broad application in material sciences. − In organic synthesis, they are of immense importance and treated as cross-coupling, ,,− radical coupling, , and germanium-halogen exchange partners. , Moreover, organogermanium compounds were also added as the selective organic toolbox where the orthogonal reactivity for the cross-coupling reactions between aromatic rings can be attained over organoboranes, organosilanes, and organohalides using nanoparticle catalysis. ,, …”

Earth-Abundant Heterogeneous Cobalt Catalyst for Selective Ring Hydrogenation of (Hetero)arenes and Gram-Scale Synthesis of Pharmaceutical Intermediates

“…Over the last few years, Glorious, , Zeng, and other research groups employed homogeneous rhodium–carbene catalysts, i.e., Rh­(CAAC) (CAAC = cyclic alkyl amino carbene) for the chemoselective hydrogenation of (multi)­fluoroarenes, ,, borylated arenes, silylated arenes, and aromatic ketones . Furthermore, Ru, − Os, W, Mo, Pd, , and Ir − complexes have also shown very good catalytic performance for the regioselective hydrogenation of arenes and heteroarenes, including polycyclic aromatic compounds.…”

Ru-NHC-Catalyzed Asymmetric, Complete Hydrogenation of Indoles and Benzofurans: One Catalyst with Dual Function

“…The transformation and utilization of inexpensive and readily available arenes have become a principal area of research. − The complete hydrogenation of arenes − is one of the most effective methods for converting planar molecules into saturated three-dimensional structures, which are critical building blocks in many aspects of life. ,− However, asymmetric hydrogenation of arenes has historically been a major challenge due to the lack of enantioselective catalysts, and the successful cases have largely been confined to the rings with weak aromaticity, such as heteroaromatic rings ,− and fused arenes. − The combination of heterogeneous and homogeneous catalysis has proven to be a promising method for hydrogenation of aromatic compounds. − Recently, Andersson’s group utilized an excessive amount of ligands compared to the Rh precursor to generate both homo- and heterogeneous catalysts in the reaction. Subsequently, they took advantage of the high reaction rate of homogeneous hydrogenation and the induction period of heterogeneous hydrogenation to achieve an asymmetric and complete reduction of arenes (Figure a) .…”