Concise synthesis of Azilect via cobalt-catalyzed enantioselective hydrogenation in a bio-based solvent

Abstract

An asymmetric synthesis of Rasagiline (Azilect), an anti Parkinson’s therapeutic, was developed employing an earth-abundant metal catalyst in a bio-based solvent. The asymmetric hydrogenation of the indanone-derived enamide was performed...

Cobalt‐Catalyzed Asymmetric Hydrogenation: Substrate Specificity and Mechanistic Variability

“…The hydrogenation of indanone‐derived enamide using Co/ Ph BPE was found to proceed as an isomerization (enamide‐imide) free direct C=C hydrogenation with molecular H 2 . Several control experiments and electron paramagnetic resonance (EPR) results also showed the involvement of a redox active Co(0)/Co(II) catalytic cycle promoted by Zn as 2e − reductant [43] …”

“…Several control experiments and electron paramagnetic resonance (EPR) results also showed the involvement of a redox active Co(0)/Co(II) catalytic cycle promoted by Zn as 2e À reductant. [43]…”

Cobalt‐Catalyzed Asymmetric Hydrogenation: Substrate Specificity and Mechanistic Variability

“…[41] Employing a similar catalyst with cyclic enamides as substrate [38] de Vries and co-workers recently reported the synthesis of (R)-Rasagiline (Azilect: treatment of Parkinson's disease) via Co/ Ph BPE-catalyzed asymmetric hydrogenation as the key step for enantio-induction (Scheme 10). [43] The "amide effect" in enamide hydrogenation was also investigated by varying the alkyl and aryl part at the carbonyl group of the amides (Scheme 10). A modest variation in ee was found (NHCO i Pr (88 %) < NHCOMe (89 %) < NHCOPh (94 %)).…”

“…Asymmetric hydrogenation of 1-indanone derived enamides and Azilect synthesis using Co/BPE. [43] nearly quantitative yield. [17a] A breakthrough was achieved in 1981 by Ohgo and co-workers, when they combined the Co II (dmg) with chiral amino alcohols such as the cinchona alkaloids, which allowed the asymmetric hydrogenation of diketones, α-keto-esters, α,β-unsaturated ketones and esters and acylated dehydroamino acid esters (Scheme 12).…”