Synthesis of Chiral Trifluoromethyl-Substituted Hydrazines via Pd-Catalyzed Asymmetric Hydrogenation and Reductive Amination

Chen, Zhang‐Pei; Hu, Shu-Bo; Ji, Zhou; Zhou, Yong‐Gui

doi:10.1021/acscatal.5b01641

Cited by 55 publications

(20 citation statements)

References 58 publications

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“…The reductive reactions of inorganic ammonia and ammonium salts, such as ammonium acetate and ammonium salicylate, with functionalized [6] and simple ketones [7] were catalyzed by ruthenium‐diphosphine complexes to afford exclusively α‐chiral primary amines, which are important building blocks (Scheme 1 a I). Primary amines including anilines, [2a, 8] benzylamine, [9] hydrazines, [10] and hydrazides [8e, 11] have been utilized as the organic amine sources to form the corresponding secondary chiral amines (Scheme 1 a II). Very recently, and with the help of multiple additives, secondary amines were effectively employed as N sources in direct ARA to afford tertiary chiral amines (Scheme 1 a II) [12] .…”

Section: Methodsmentioning

confidence: 99%

An Iridium Catalytic System Compatible with Inorganic and Organic Nitrogen Sources for Dual Asymmetric Reductive Amination Reactions

Gao

Huang

et al. 2021

Angew Chem Int Ed

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Asymmetric reductive amination (ARA) is one of the most promising methods for the synthesis of chiral amines. Herein we report our efforts on merging two ARA reactions into a single‐step transformation. Catalyzed by a complex formed from iridium and a steric hindered phosphoramidite, readily available and inexpensive aromatic ketones initially undergo the first ARA with ammonium acetate to afford primary amines, which serve as the amine sources for the second ARA, and finally provide the enantiopure C2‐symmetric secondary amine products. The developed process competently enables the successive coupling of inorganic and organic nitrogen sources with ketones in the same reaction system. The Brønsted acid additive plays multiple roles in this procedure: it accelerates the formation of imine intermediates, minimizes the inhibitory effect of N‐containing species on the iridium catalyst, and reduces the primary amine side products.

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Section: Methodsmentioning

confidence: 99%

An Iridium Catalytic System Compatible with Inorganic and Organic Nitrogen Sources for Dual Asymmetric Reductive Amination Reactions

Gao

Huang

et al. 2021

Angew Chem Int Ed

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“…Over the recent fifteen years, palladium complexes have been successfully applied in asymmetric hydrogenation of various prochiral substrates bearing C=N double bond, including hydrazones . Considerable advances in this field and our previous experience prompted us to study an application of palladium catalysis for the synthesis of optically active α ‐amino phosphonates using α ‐hydrazono phosphonates as convenient precursors.…”

Section: Figurementioning

confidence: 99%

“…It is known that TFE serves as a “magic” solvent in homogeneous enantioselective Pd‐catalyzed hydrogenation –. However, it has been shown that its dilution with such low‐polarity solvents as toluene or dichloromethane have had a good effect in some cases.…”

Section: Figurementioning

confidence: 99%

One‐Pot Two‐Step Synthesis of Optically Active α‐Amino Phosphonates by Palladium‐Catalyzed Hydrogenation/Hydrogenolysis of α‐Hydrazono Phosphonates

et al. 2016

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An efficient and convenient one-pot procedure for the stereoselective catalytic synthesis of ring-substituted [amino(phenyl)methyl]phosphonates has been developed. The enantioselective hydrogenation of easily available diisopropyl (Z)-[aryl(phenylhydrazono)methyl]phosphonates using palladium(II) acetate as a precatalyst, (R)-2,2'-bis (diphenylphosphino)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl [(R)-Cl-MeO-BIPHEP] as a ligand, and (1S)-(+)-10-camphorsulfonic acid as an activator in a mixture of 2,2,2-trifluoroethanol and methylene chloride at ambient temperature results in the formation of corresponding [aryl(2-phenylhydrazino)methyl]phosphonates. The subsequent cleavage of the NÀN bond has been accomplished with molecular hydrogen after the addition of palladium on carbon and methanol into crude reaction mixture to afford the optically active [amino(aryl)methyl]phosphonates. The method is operationally simple and provides an appreciable enantioselectivity up to 98 % ee.Keywords: a-amino phosphonates; asymmetric catalysis; a-hydrazono phosphonates; hydrogenation; palladium a-Amino phosphonates, particularly nonracemic ones, have been a topic for decades due to a wide spectrum of their possible applications.[1] Nevertheless, the stereocontrolled formation of a-amino phosphonates remains a challenge in chemical synthesis. Among catalytic concepts for the enantioselective synthesis of a-amino phosphonates, two methodologies are leading, namely, asymmetric hydrophosphonylation of aldimines and ketimines and asymmetric reduction of a,b-dehydroaminophosphonates.[2] Several years ago we reported on the feasibility of Rh-catalyzed asymmetric hydrogenation of a-imino phosphonates as a straightforward access to optically active a-amino phosphonates containing the quaternary b-carbon atom.[3] Subsequently, this approach was extended on oxazaborolidine catalyzed reduction of (2,2,2-trifluoro-1-iminoethyl)phosphonates with catecholeborane.[4] Along with all apparent advantages, some pitfalls of this method should be mentioned. First, aimino phosphonates are actually an equilibrium mixture of Z/E-isomers, which may have an adverse effect on the overall stereoselectivity of the process. In addition, these starting substrates are slowly hydrolyzed on storage. Finally, the common synthesis of aimino phosphonates via the Michaelis-Arbuzov rearrangement requires the usage of labile imidoyl chlorides under harsh reaction conditions.[5] When the present paper was in preparation, Zhou et al. communicated on excellent results in Pd-catalyzed asymmetric hydrogenation of a-tosylimino phosphonates. [6] However, the latter precursors cannot be considered the best choice, because they are synthesized from the same racemic a-tosylamino phosphonates by N-chlorination/dehydrochlorination procedure. [7] Readily accessible a-oxo phosphonates [8] are important reagents for the preparation of elaborate phosphonates. Unfortunately, they cannot be used for the synthesis of the corresponding a-imino phosphonates since the interaction of si...

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“…[17] Unlike α-trifluoromethylated amines, α-trifluoromethylated hydrazones are relatively less explored as substrates in the drug design, presumably owing to the synthetic challenges involved in the preparation of these compounds. The α-trifluoromethyl hydrazones can be hydrogenated to give the corresponding hydrazines, which are useful substrates in the preparation of the pharmaceutically interesting compounds, [18] or hydrolyzed to give the trifluoromethyl ketones, which are used as serine protease inhibitors in the drug design. [19,20] Aldehyde or ketone hydrazones, in contrast to the related imines, do not undergo nucleophilic trifluoromethylations because the electrophilicity of the imino carbon is attenuated due to the resonance interaction of the adjacent amino group.…”

Section: Introductionmentioning

confidence: 99%

Cu‐Catalyzed C(sp²−H)‐Trifluoromethylation of Aldehyde Hydrazones with Langlois Reagent

2021

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The C(sp 2 À H)-trifluoromethylation of hydrazones would give access to the α-trifluoromethylated hydrazones that can serve as intermediates in the synthesis of pharmaceutically interesting fluorinated compounds. Herein, we demonstrate the Cu-catalyzed C(sp 2 À H)-trifluoromethylation of the aldehyde hydrazones using the readily available and cost effective Langlois reagent (sodium trifluoromethanesulfinate). This reaction is broadly applicable to a series of aromatic aldehyde N-aminomorpholine hydrazones to give the corresponding C(sp 2 )-trifluoromethyl hydrazones in moderate to high yields. The reaction generally tolerates a series of electron-releasing as well as electronwithdrawing substituents on the aromatic ring.

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Synthesis of Chiral Trifluoromethyl-Substituted Hydrazines via Pd-Catalyzed Asymmetric Hydrogenation and Reductive Amination

Cited by 55 publications

References 58 publications

An Iridium Catalytic System Compatible with Inorganic and Organic Nitrogen Sources for Dual Asymmetric Reductive Amination Reactions

An Iridium Catalytic System Compatible with Inorganic and Organic Nitrogen Sources for Dual Asymmetric Reductive Amination Reactions

One‐Pot Two‐Step Synthesis of Optically Active α‐Amino Phosphonates by Palladium‐Catalyzed Hydrogenation/Hydrogenolysis of α‐Hydrazono Phosphonates

Cu‐Catalyzed C(sp²−H)‐Trifluoromethylation of Aldehyde Hydrazones with Langlois Reagent

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Synthesis of Chiral Trifluoromethyl-Substituted Hydrazines via Pd-Catalyzed Asymmetric Hydrogenation and Reductive Amination

Cited by 55 publications

References 58 publications

An Iridium Catalytic System Compatible with Inorganic and Organic Nitrogen Sources for Dual Asymmetric Reductive Amination Reactions

An Iridium Catalytic System Compatible with Inorganic and Organic Nitrogen Sources for Dual Asymmetric Reductive Amination Reactions

One‐Pot Two‐Step Synthesis of Optically Active α‐Amino Phosphonates by Palladium‐Catalyzed Hydrogenation/Hydrogenolysis of α‐Hydrazono Phosphonates

Cu‐Catalyzed C(sp2−H)‐Trifluoromethylation of Aldehyde Hydrazones with Langlois Reagent

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Cu‐Catalyzed C(sp²−H)‐Trifluoromethylation of Aldehyde Hydrazones with Langlois Reagent