Asymmetric Hydrogenation of Heteroaromatic Ketones and Cyclic and Acyclic Enones Mediated by Cu(I)-Chiral Diphosphine Catalysts

Abstract

Copper(I)-catalyzed asymmetric hydrogenation of heteroaromatic ketones, cyclic and acyclic enones is reported. The choice of the chiral diphosphine ligand highly influenced enantioselectivity as well as chemoselectivity. Highly enantioselective hydrogenation of ortho-substituted heteroaromatic ketones was achieved using BDPP as the ligand. In the 1,2-selective hydrogenation of acylic enone, SEGPHOS gave higher enantioselectivity than BDPP. On the other hand, the bulky ligand DTBM-SEGPHOS had a 1,4-selective nature, leading to the first highly 1,4-selective and enantioselective hydrogenation of cyclic enones.

Key words

asymmetric catalysis - hydrogenations - copper - heteroaromatic ketones - enones

References and Notes

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8

The reaction with additional 3 equiv of P(3,5-xylyl)₃ gave an almost identical result.

14

The reaction using BDPP and SEGPHOS instead of DTBM-SEGPHOS under the reaction conditions of entry 2 resulted in low conversion and low chemoselectivity. (S,S)-BDPP: conv. 25%, 8/9/10 = 53:11:36. R-SEGPHOS: conv. 17%,
8/9/10 = 11:18:70.

15

Asymmetric hydrogenation of 3-methylcyclohex-2-enone under the reaction conditions described in Table  [³] , entry 4 resulted in 51% conversion, allylic alcohol/sat. ketone/sat. alcohol = 2:61:37, 30% yield of sat. ketone, 92% ee (R) of sat. ketone (not optimized).

17

Formation of the fully sat. ketone, menthone, was <1% based on GC analysis.