Synfacts 2017; 13(11): 1174
DOI: 10.1055/s-0036-1591395
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Tetrahydropyrrolo[1,2-a]pyr-azines by Asymmetric Hydrogenation

Contributor(s):
Mark Lautens
,
Marcus Wegmann
Hu S.-B. Chen Z.-P. Song B. Wang J. Zhou Y.-G. * Dalian Institute of Chemical Physics, P. R. of China
Enantioselective Hydrogenation of Pyrrolo[1,2-a]pyrazines, Heteroaromatics Containing Two Nitrogen Atoms.

Adv. Synth. Catal. 2017;
359: 2762-2767
Further Information

Publication History

Publication Date:
19 October 2017 (online)

 

Significance

Although the asymmetric hydrogenation of nitrogen-containing heterocycles has been studied extensively over the past years, the same strategy remains underinvestigated for heterocycles with multiple nitrogen atoms. One of the hurdles to overcome is the low reactivity of these substrates. To date, common approaches to achieve the enantioselective hydrogenation use more active substrates such as the benzylated or protonated forms. In the present paper, the authors disclose the asymmetric hydrogenation of substituted and unactivated heterocycles.


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Comment

The reaction generally delivers the desired products in excellent yields and enantioselectivities, although some examples show diminished enantiomeric excess. In one example, enantioselective hydrogenation of a 3,4-disubstituted substrate has been achieved with excellent diastereoselectivity, albeit with acid as an activator. Deuterium-labeling studies, in combination with reaction monitoring by NMR, suggest that the first hydrogenation takes place at the 3- and 4-position of the heterocycle.


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