Science of Synthesis

Llopis, Q.; Ayad, T.; Phansavath, P.; Ratovelomanana-Vidal, V., Science of Synthesis: Catalytic Reduction in Organic Synthesis, (2018) 2, 122.

The asymmetric hydrogenation of β-amino ketones bearing a secondary amino group to give the corresponding enantiopure N-monosubstituted γ-amino alcohols is a challenging task due to the deamination reaction that can occur during the process, resulting in the formation of α,β-unsaturated ketones. This difficult issue has been circumvented by using rhodium complexes containing electron-rich bisphosphine ligands such as DuanPhos (‌49‌)[‌60‌] and BenzP* (‌69‌).[‌61‌] As shown in ‌Scheme 28‌, various aryl/hetaryl β-aminoalkyl ketones, as the corresponding hydrochloride salts, can be efficiently reduced to give γ-amino alcohols ‌70‌ and ‌71‌ in good yields and with high asymmetric induction. In these processes, the hydrogen chloride is crucial for avoiding formation of the deamination side product, by stabilizing the free β-amino ketone. Similar results in terms of yields and selectivities have also been obtained for the asymmetric hydrogenation of both secondary[‌62‌] and tertiary[‌63‌] amino ketone derivatives by using a triruthenium complex featuring a phosphinoruthenocenyl unit and two oxazoline units.

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References