The homogeneous catalyzed dehydrogenation of methanol in a synthetically valuable cross-coupling reaction was achieved. By the use of a simple ruthenium-N-heterocyclic carbene complex, MeOH and primary or secondary amines can be converted into formamides.

Optically active six-membered rings such as cyclohexanes and piperidines play an important role as biologically active building blocks and key intermediates in organic chemistry. Catalytic asymmetric hydrogenation of aromatic and heteroaromatic compounds is one of the most straightforward routes for the formation of these saturated or partially saturated molecules.[1] Recently, tremendous progress has been made in asymmetric reduction of bicyclic heteroaromatic compounds such as quinoxalines, [2] quinolines, [3] and indoles, [4] and excellent yields and enantioselectivities have been obtained. However, in all these cases, only the reduction of the nitrogen-containing ring was reported, which creates a stereogenic center in the 2-or 3-position. Remarkably, to our knowledge, there are no reports of homogeneous asymmetric hydrogenation of these substrates in which the carbocyclic ring is selectively reduced.[5] Possible reasons include 1) a high level of aromatic stabilization in the benzene ring, 2) its lower ability to coordinate to the metal center, and 3) the general difficulty of discrimination between the enantiotopic faces. Nevertheless, an interesting non-asymmetric example of such a regioselective hydrogenation of nitrogen-containing bicyclic aromatic compounds was reported by Borowski, Sabo-Etienne, and co-workers. [6] Using the bis(dihydrogen) complex [RuH 2 (h 2 -H 2 ) 2 (PCy 3 ) 2 ] (Cy = cyclohexyl), unsubstituted compounds such as quinoline and isoquinoline could be selectively reduced to their corresponding 5,6,7,8-tetrahydro derivatives. In view of our general interest in the synthesis and application of Nheterocyclic carbenes (NHCs) [7] in asymmetric catalysis, [8] we were interested in utilizing these ligands in the challenging asymmetric hydrogenation of aromatic substrates. Herein, we report a highly regioselective method for the homogeneous, asymmetric hydrogenation of substituted quinoxalines using a chiral ruthenium NHC complex. Ruthenium NHC complexes have found many applications, [7f] most prominently in olefin metathesis reactions.[7l]Recently, Beller et al. reported the successful application of Ru NHC complexes formed in situ from [Ru(cod)(2-methylallyl) 2 ] (1; cod = cyclooctadiene) and achiral monodentate NHCs in the transfer hydrogenation of ketones [9a] and in the selective reduction of nitriles to primary amines.[9b] In the course of our research on the asymmetric hydrogenation of heteroaromatic compounds, we found that the combination of 1 and monodentate NHCs leads to very reactive catalytic systems for the hydrogenation of quinoxalines. By using the catalyst generated in situ from 1 and N,N-bis(2,6-diisopropylphenyl)dihydroimidazol-2-ylidene (SIPr), the model substrate 2 a could be quantitatively reduced to the corresponding 1,2,3,4-tetrahydroquinoxaline 3 a as the only observable regioisomer (Scheme 1, path I; see also Table 1, entry 2).[10]

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An efficient and highly asymmetric ruthenium-N-heterocyclic carbene-catalyzed hydrogenation of substituted thiophenes and benzothiophenes is described, providing a new strategy for the formation of valuable enantiomerically pure tetrahydrothiophenes and 2,3-dihydrobenzothiophenes.