Scale-Up of an Enantioselective Overman Rearrangement for an Asymmetric Synthesis of a Glycine Transporter 1 Inhibitor

Chandramouli, Sithamalli V.; Ayers, Timothy A.; Wu, Xiaodong; Tran, Loc T.; Peers, James H.; DiSanto, Rocco; Roberts, F. E.; Kumar, Narendra; Jiang, Ying; Choy, Nakyen; Pemberton, Clive; Powers, Matthew R.; Gardetto, Anthony J.; D’Netto, Geoffrey A.; Chen, Xuemin; Gamboa, Juan A.; Ngô, Đức Quang; Copeland, Warren R.; Rudisill, Duane E.; Bridge, Andrew W.; Vanasse, Benoit; Lythgoe, David J.

doi:10.1021/op200378r

Cited by 11 publications

(5 citation statements)

References 28 publications

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“…37,38 The Ru-catalyzed asymmetric transfer hydrogenation of cyclic ketones provides a convenient approach to enantio-enriched cyclic alcohols. Large-scale transformations of this type have been conducted in the pharmaceutical industry for the preparation of chiral drugs quinuclidine (47) 39 and eslicarbozepine acetate (50). 40 As shown in Scheme 11, cyclic ketones 45 based on a quinuclidine skeleton and oxcarbazepine 48 were reduced enantioselectively by using proper Ru-diamine catalysts to chiral alcohols 46 and 49, respectively.…”

Section: Asymmetric (Transfer) Hydrogenationmentioning

confidence: 99%

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Yang

Stolarzewicz

et al. 2023

Chem. Rev.

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The proportion of approved chiral drugs and drug candidates under medical studies has surged dramatically over the past two decades. As a consequence, the efficient synthesis of enantiopure pharmaceuticals or their synthetic intermediates poses a profound challenge to medicinal and process chemists. The significant advancement in asymmetric catalysis has provided an effective and reliable solution to this challenge. The successful application of transition metal catalysis, organocatalysis, and biocatalysis to the medicinal and pharmaceutical industries has promoted drug discovery by efficient and precise preparation of enantio-enriched therapeutic agents, and facilitated the industrial production of active pharmaceutical ingredient in an economic and environmentally friendly fashion. The present review summarizes the most recent applications (2008–2022) of asymmetric catalysis in the pharmaceutical industry ranging from process scales to pilot and industrial levels. It also showcases the latest achievements and trends in the asymmetric synthesis of therapeutic agents with state of the art technologies of asymmetric catalysis.

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Section: Asymmetric (Transfer) Hydrogenationmentioning

confidence: 99%

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Yang

Stolarzewicz

et al. 2023

Chem. Rev.

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“…[5] As ar esult of the synthetic utility of chiral enantiopurea llylic amines,anumber of catalytic methods have been developed for the enantioselective preparation including allylic substitutions, [6] 1,2-additions of appropriate nucleophiles to imines, [7] hydrogenations of dienamines, [8] hydroaminationso fa llenes [9] and severalt ypes of rearrangements. The latter include [1,3]-, [10] [2,3]- [11] and [3,3]-rearrangements. [12] Predominantly allylic imidate substrates 5 (see Scheme 1, dashed box) in combination with carbophilic Lewis acids have been employed for enantioselective [3,3]-rearrangements.…”

Section: Introductionmentioning

confidence: 99%

“…Enantiopure α‐branched allylic amines are employed as high‐value building blocks for technical scale applications because the synthetically versatile amino and olefin functionalities allow for a number of subsequent synthetic manipulations. For that reason chiral allylic amines have also been used in a large number of natural product syntheses, for a straightforward access towards N‐containing chiral heterocycles as well as α‐ or β‐amino acids .…”

Section: Introductionmentioning

confidence: 99%

Dual Palladium(II)/Tertiary Amine Catalysis for Asymmetric Regioselective Rearrangements of Allylic Carbamates

Bauer

Frey

Peters

2016

Chemistry A European J

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The streamlined catalytic access to enantiopure allylic amines as valuable precursors towards chiral β- and γ-aminoalcohols as well as α- and β-aminoacids is desirable for industrial purposes. In this article an enantioselective method is described that transforms achiral allylic alcohols and N-tosylisocyanate in a single step into highly enantioenriched N-tosyl protected allylic amines via an allylic carbamate intermediate. The latter is likely to undergo a cyclisation-induced [3,3]-rearrangement catalysed by a planar chiral pentaphenylferrocene palladacycle in cooperation with a tertiary amine base. The otherwise often indispensable activation of palladacycle catalysts by a silver salt is not required in the present case and there is also no need for an inert gas atmosphere. To further improve the synthetic value, the rearrangement was used to form dimethylaminosulfonyl-protected allylic amines, which can be deprotected under non-reductive conditions.

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“…[1][2][3][4][5][6] They are usually prepared in good yields under basic conditions by an aldol condensation between 3-quinuclidinone hydrochloride and an aldehyde.…”

Section: Introductionmentioning

confidence: 99%

“…[4] Chirality can be introduced through tautomerization using chiral acids [5] or by asymmetric carbonyl reduction. [6] However, with this approach, it is difficult to introduce functional groups at positions other than the α,β-unsaturated system. The only known procedure for functionalization at other sites in these α,β-unsaturated quinuclidines is hydroxylation with enzymes.…”

Section: Introductionmentioning

confidence: 99%