Highly Enantioselective Synthesis of Sitagliptin

Khopade, Kishor V.; Sen, Anirban; Birajdar, Rajkumar S.; Paulbudhe, Uday P.; Kavale, Dattatry S.; Shinde, Prashant S.; Mhaske, Santosh B.; Chikkali, Samir H.

doi:10.1002/ajoc.201900709

Cited by 7 publications

(5 citation statements)

References 26 publications

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“…We then tested L1 in Ru-catalyzed asymmetric hydrogenations of unprotected enamine 11. To our delight, L1 also worked quite well, providing the enantiomer of an antidiabetic drug (+)-sitagliptin 22 on the gram scale, with 83% yield, and an almost enantiomerically pure form (>99% ee), which is comparable with the Ru/DM-SegPhos catalytic system. 23 Furthermore, by using L1, (S,S)-DPEN, and (R,R)-DPEN, we prepared two diphosphine/diamine-Ru complexes RuCl 2 (L1)[(S,S)-DPEN] and RuCl 2 (L1)[(R,R)-DPEN] (Scheme 3).…”

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confidence: 87%

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Design and Synthesis of Diphosphine Ligands Based on the Chiral Biindolyl Scaffold and Their Application in Transition-Metal Catalysis

Zhang,

Chen,

Zhang

2024

Org. Lett.

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An extremely concise, scalable, and stereoselective synthesis of a privileged chiral skeleton based on 2,2′-biindolyl and commercially available chiral building blocks has been developed. This novel skeleton allows for easy access to a range of bisphosphine ligands (decagram scale, up to 58% total yield, only three steps). The synthetic method is characterized by an efficient central-to-axial chirality transfer strategy. In particular, the superior performance of the ligands has been demonstrated in diverse reactions, including several asymmetric hydrogenations, asymmetric conjugate reductions, and cycloisomerization reactions, indicating a great potential for the application of the newly developed chiral backbones in further modifications and exploration of novel chiral ligands and catalysts.

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confidence: 87%

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confidence: 98%

Design and Synthesis of Diphosphine Ligands Based on the Chiral Biindolyl Scaffold and Their Application in Transition-Metal Catalysis

Zhang,

Chen,

Zhang

2024

Org. Lett.

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“…More recently, Chikkali and co-workers reported that Rh complexes bearing chiral FerroLANE ligands also catalyze the AH of S110 to yield sitagliptin with excellent enantioselectivity (98% ee). 406 The asymmetric synthesis of P110 was also accomplished via direct asymmetric reductive amination (ARA) with unprecedented levels of asymmetric induction. 407 In addition, Ru catalysis has been successfully applied in both ARA or direct AH of unprotected enamines for the preparation of other pharmacologically relevant compounds.…”

Section: Unprotected Enaminesmentioning

confidence: 99%

“…P110 was obtained in 98% yield and 95% ee (improved to >99% ee by recrystallization) using (R C ,R p ) -L21a . More recently, Chikkali and co-workers reported that Rh complexes bearing chiral FerroLANE ligands also catalyze the AH of S110 to yield sitagliptin with excellent enantioselectivity (98% ee) . The asymmetric synthesis of P110 was also accomplished via direct asymmetric reductive amination (ARA) with unprecedented levels of asymmetric induction .…”

Section: Asymmetric Hydrogenation Of Enaminesmentioning

confidence: 99%

Recent Advances in the Enantioselective Synthesis of Chiral Amines via Transition Metal-Catalyzed Asymmetric Hydrogenation

2021

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Chiral amines are key structural motifs present in a wide variety of natural products, drugs, and other biologically active compounds. During the past decade, significant advances have been made with respect to the enantioselective synthesis of chiral amines, many of them based on catalytic asymmetric hydrogenation (AH). The present review covers the use of AH in the synthesis of chiral amines bearing a stereogenic center either in the α, β, or γ position with respect to the nitrogen atom, reported from 2010 to 2020. Therefore, we provide an overview of the recent advances in the AH of imines, enamides, enamines, allyl amines, and N-heteroaromatic compounds.

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“…The transition metal‐catalyzed asymmetric hydrogenation of alkenes using chiral ligand is an essential tool to obtain chiral pharmaceuticals [21] . The conventional AH model utilizes either monodentate ligands that suffer from limited selectivity or bidentate ligands which are more selective but less reactive and require tedious synthesis [22,23] .…”

Section: Introductionmentioning

confidence: 99%

Phosphorus Ligands in Hydroformylation and Hydrogenation: A Personal Account

Tewari

Kumar

Chandanshive

et al. 2021

The Chemical Record

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Metal‐catalyzed hydroformylation and hydrogenation heavily rely on ligands, among which phosphorous ligands play a pivotal role. This personal account presents a selection of three distinct classes of phosphorous ligands, namely, monodentate meta‐substituted phosphinites, bis‐phosphites, and P‐chiral supramolecular phosphines, developed in our group. The synthesis of these ligands, isolation, characterization, and their performance in transition metal‐catalyzed hydroformylation, isomerizing hydroformylation, and asymmetric hydrogenation of olefins is summarized. The state of the art development in iron‐catalyzed hydroformylation of alkenes and our contributions to the field is discussed. Use of phosphines enabled iron‐catalyzed hydroformylation of alkenes under mild conditions. Thus, this account demonstrates the central role of phosphorus ligands in industrially relevant transformations such as hydrogenation and hydroformylation. The seemingly matured field of ligand discovery still holds significant potential and will steer the field of homogeneous catalysis.

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Highly Enantioselective Synthesis of Sitagliptin

Cited by 7 publications

References 26 publications

Design and Synthesis of Diphosphine Ligands Based on the Chiral Biindolyl Scaffold and Their Application in Transition-Metal Catalysis

Design and Synthesis of Diphosphine Ligands Based on the Chiral Biindolyl Scaffold and Their Application in Transition-Metal Catalysis

Recent Advances in the Enantioselective Synthesis of Chiral Amines via Transition Metal-Catalyzed Asymmetric Hydrogenation

Phosphorus Ligands in Hydroformylation and Hydrogenation: A Personal Account

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