Identification of Ammonium Chloride as an Effective Promoter of the Asymmetric Hydrogenation of a β-Enamine Amide

Clausen, Ashley; Dziadul, Brianne; Cappuccio, Kristine L.; Kaba, Mahmoud S.; Starbuck, Cíndy; Hsiao, Yi; Dowling, Thomas M.

doi:10.1021/op050232o

Cited by 62 publications

(25 citation statements)

References 8 publications

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“…Many publications appeared treating the problem of the synthesis of this compound and its derivatives. For instance, a scheme of asymmetric synthesis of the sitagliptin phosphate from the precursor, α,β-enamine amide, is given in [ 152 ]. A wide search for effective antidiabetic agents was performed among the homologues of this compound; therewith the varied structural parameter was the substituent in the phenyl ring [ 153 ] and also the substituents in the piperazine fragment [ 154 ].…”

Section: Antidiabeticsmentioning

confidence: 99%

Fluorinated Triazoles and Tetrazoles

Островский

Trifonov

2014

Fluorine in Heterocyclic Chemistry Volume 1

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Section: Antidiabeticsmentioning

confidence: 99%

Fluorinated Triazoles and Tetrazoles

Островский

Trifonov

2014

Fluorine in Heterocyclic Chemistry Volume 1

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“…Commercial manufacture of the drug substance involves an enantioselective hydrogenation of an unprotected b-enamine amide 131 (Scheme 29.6). 191 It was shown that asymmetric hydrogenation of 131 can carried out at 50 C in methanol in the presence of chiral Rh (I)-catalysts prepared from [Rh(COD)Cl] 2 and Josiphos SL-J002-1 ligand (Solvias) under 100 psig (or 115 psi) of H 2 -pressure to achieve 82-99% conversions in to chiral amine 132 with enantioselectivity ranging from 89% to 95% ee. 191 Further extensive screenings on a search for the most suitable catalyst for the highly enantioselective hydrogenation of 131 provided in collaboration with Solvias revealed that also other ligands, even ones outside the ferrocenyl structural class, could effect this transformation with high enantioselectivity.…”

Section: Rhodium-catalyzed Stereoselective Hydrogenation Of Functionamentioning

confidence: 99%

Stereoselective Hydrogenation ofCCBonds: Application to Drug and Natural Product Synthesis

Andrushko

2013

Stereoselective Synthesis of Drugs and Natural Products

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Asymmetric homogeneous hydrogenation is perhaps one of the most researched areas in homogeneous catalysis; thus, it is now used in numerous innovative applications in stereoselective syntheses of many chiral pharmaceutical and natural products. Metal complexes, derived from transition metals, like Rh, Ru, Ir, and so on, and chiral ligands (usually mono‐ or diphosphine ligands), are widely used as catalysts in asymmetric alkene hydrogenation as a result of their efficiency in the preparation of enantiopure compounds with excellent atom economy. This chapter provides many interesting examples of homogeneous enantio‐ and diastereoselective hydrogenation of CC bonds, highlighting the utility of these methods as useful synthetic tools for the construction of stereogenic centers in stereoselective drug and natural product syntheses.

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“…Subsequent recrystallization and salt formation with phosphoric acid gave Januvia® (sitagliptin phosphate, 8 ). Efforts to optimize efficiency and examine the mechanism of the asymmetric process revealed a reactivity and selectivity dependence on the pH of the reaction solution 39. It was found that ∼1 mol% of a mild acid (i.e., ammonium chloride) was essential for the reaction to proceed reproducibly on large scale.…”

Section: β-Enamino Amide Hydrogenations – Januvia®mentioning

confidence: 99%

Natural products as inspiration for the development of asymmetric catalysis

Mohr

Krout

Stoltz

2008

Nature

229

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Biologically active natural products often contain particularly challenging structural features and functionalities. Perhaps foremost among these difficulties are issues of stereochemistry. A useful strategy for synthesizing these molecules is to devise novel methods of bond-formation that provide new opportunities for enantioselective catalysis. In using this tactic, target structures define the problems to be solved and ultimately drive development of catalysis forward. New enantioselective methods discovered in the context of these total synthesis efforts then contribute to a greater understanding of fundamental bond construction and lead to valuable synthetic technologies useful for a variety of other applications.Inasmuch as retrosynthetic analysis 1 enables synthetic planning toward valuable chemical substances, one can be easily discouraged by a lack of methods to install particular functionalities or structural motifs present in the target molecule. Still more difficult is adapting a strategic approach to incorporate the relatively limited number of catalytic enantioselective transformations to allow preparation of enantioenriched materials for further studies. 2,3,4,5, 6 However, when encountering the structural challenges presented by important natural products and pharmaceutical compounds a fruitful strategy is to design a synthesis that hinges upon a particular bond disconnection that is beyond the present lexicon of enantioselective transformations. Employing this strategy, the structures of target molecules provide the impetus for the development of novel transformations and lead to a greater fundamental understanding of methods of bond construction and catalysis. In this Review several recent examples of novel catalytic enantioselective transformations demonstrate the effectiveness of this useful strategy for the preparation of important structural motifs found in biologically active molecules. Each example has contributed not only an effective means of accessing a particular target structure, but also a useful new tool for a variety of further applications in synthetic chemistry.To provide an overview of established catalytic enantioselective methods developed in the context of total synthesis, several notable examples are highlighted in Figure 1. In each of these cases, the target molecules posed particular challenges that had not yet been solved by enantioselective catalysis. Although in some instances (e.g., Diels-Alder reaction, Figure 1a) the methods were developed before their first applications in total synthesis, but the demonstrated value of the transformation served to further highlight the need for enantioselective variants. Subsequent to the development of the [4 + 2] cycloaddition by Diels and Alder in the 1920s, 7 many studies of this transformation elucidated several key facets of Correspondence should be addressed to B.M.S. (email: stoltz@caltech.edu).. † These authors contributed equally to this manuscript.The authors declare no competing financial interests. NIH Public ...

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Identification of Ammonium Chloride as an Effective Promoter of the Asymmetric Hydrogenation of a β-Enamine Amide

Cited by 62 publications

References 8 publications

Fluorinated Triazoles and Tetrazoles

Fluorinated Triazoles and Tetrazoles

Stereoselective Hydrogenation ofCCBonds: Application to Drug and Natural Product Synthesis

Natural products as inspiration for the development of asymmetric catalysis

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