A One-Pot Process for the Enantioselective Synthesis of Amines via Reductive Amination under Transfer Hydrogenation Conditions

Williams, Glynn D.; Pike, Richard A.; Wade, Charles E.; Wills, Martin

doi:10.1021/ol035746r

Cited by 145 publications

(55 citation statements)

References 25 publications

(20 reference statements)

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“…Dichloromethane was found to be the best solvent for the reaction. The solvent was changed to CHCl 3 , CCl 4 , DCE, toluene, MeCN, and THF, and all of them caused a lower yield of the desired product 3a (Table 1, entries 14−19). When the amount of HMPA was reduced to 10 mol %, the yield of the product 3a dropped to 78%.…”

Section: Irect Reductive Amination (Dra) Represents a Convenientmentioning

confidence: 99%

Reductive Hydrazination with Trichlorosilane: A Method for the Preparation of 1,1-Disubstituted Hydrazines

Wang

et al. 2016

Org. Lett.

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A straightforward and facile method has been developed to prepare 1,1-disubstituted hydrazines via Lewis base promoted direct reductive hydrazination. Under the catalysis of hexamethylphosphoramide (HMPA) and N,Ndimethylacetamide (DMAc), respectively, various ketones and aldehydes could react with phenylhdrazines to prepare 1,1-disubstituted hydrazines with good to high yields. D irect reductive amination (DRA) represents a convenient and straightforward method for the synthesis of amines, which have seen wide applications in organic synthesis. 1−3 The amines that could be used as effective reactants for DRA include various primary and secondary alkyl amines, 4−6 aryl amines, 7−11 hydroxyl amines, 12 and alkoxyl amines. 13 As a special type of amines, hydrazines should in principle also be good reactants for DRA. To date, however, there have been no organocatalytic methods reported in the literature that could implement DRA using hydrazines as reactants, so-called direct reductive hydrazination (DRH). 14 Since hydrazines have two vicinal amino groups, conceivably, the difficulties confronted with DRH include the following: (1) the in situ formed hydrazone intermediate (A, Scheme 1) is normally much more stable and less reactive than the carbonyl substrates toward nucleophilic reduction; (2) the regioselectivity is hard to control if the two amino groups are both active and have different substitutions. The use of preformed hydrazones and thus indirect reductive hydrazination (IRH) method could address these difficulties to some degree, but it needs extra operations and is less convenient and economic. 15−18 Hydrosilylation of unsaturated double bonds by trichlorosilane with Lewis base as an activator is a well-known reduction method. 19−22 Its strength has been well demonstrated by others and us in asymmetric catalysis. 23−34 We were interested in extending the application of this method to DRH. The chance is that trichlorosilane should preferentially react with the terminal amino group of hydrazine 2 and leave the middle amino group to interact with the carbonyl group of 1. The resulting intermediate B should be highly active toward the hydrosilylation. Herein, we wish to communicate the results of our study and present a highly effective new method to implement DRH using organic Lewis base as promoter and trichlorosilane as reducing agent, which furnishes the condensation of various aldehydes and ketones with aryl hydrazines and reduction in one-pot under mild conditions to afford 1,1-disubstituted hydrazines as exclusive regioisomers with good to high yields.1,1-Disubstituted hydrazines 3 are important organic synthons used in a various of reactions such as Fisher indolization for the synthesis of indole and its derivatives. Kikugawa and co-workers 35 reported a four-step method to

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Section: Irect Reductive Amination (Dra) Represents a Convenientmentioning

confidence: 99%

Reductive Hydrazination with Trichlorosilane: A Method for the Preparation of 1,1-Disubstituted Hydrazines

Wang

et al. 2016

Org. Lett.

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“…[12][13][14][15][16][17] Recently some fascinating reports on asymmetric imine reduction using substituted chiral binaphthyl hydrogen phosphate as catalyst were reported by List (5h), [18] and Rueping (5g). [19] Extensive [20] and Kočovský [21] using trichlorosilane and a Lewis base organocatalyst.…”

Section: Introductionmentioning

confidence: 99%

Single Nucleotide‐Catalyzed Biomimetic Reductive Amination

2010

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Abstract:We have successfully developed a single nucleotide (adenosine 5'-diphosphate)-catalyzed enantioselective direct reductive amination of aldehydes and ketones using a Hantzsch ester as reducing agent. The process is a simple, efficient and a real mimic of the NADH reduction approach for the synthesis of structurally diverse amines. This reaction is the first report demonstrating the ability of a single nucleotide as catalyst and one of the most genuine biomimetic reactions of organic chemistry.

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“…9 Absolute configurations were obtained by comparison with the reported data. [10][11][12][13][14][15] except 34 and 36, which were assigned by analogy with 22 and 32.…”

Section: Rumentioning

confidence: 99%

“…Work-up for 2-phenyl-,3,4,5,6-tetrahydro-pyridine reduction products: The mixture was evaporated and the residue was dissolved in CHCl 3 (2 cm 3 ) and then a 1-M HCl solution (15 cm 3 ) was added and the system was stirred for 15 min. The aqueous phase was separated and turned into basic (pH [12][13][14] and extracted with DCM (3 Â 15 mL). The organic layer was separated, dried over anhydrous MgSO 4 , and evaporated providing the pure amine.…”

Section: Compound 15mentioning

confidence: 99%

Applications of N′-alkylated derivatives of TsDPEN in the asymmetric transfer hydrogenation of CO and CN bonds

Martins

Redondo

Wills

2010

Tetrahedron: Asymmetry

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A One-Pot Process for the Enantioselective Synthesis of Amines via Reductive Amination under Transfer Hydrogenation Conditions

Cited by 145 publications

References 25 publications

Reductive Hydrazination with Trichlorosilane: A Method for the Preparation of 1,1-Disubstituted Hydrazines

Reductive Hydrazination with Trichlorosilane: A Method for the Preparation of 1,1-Disubstituted Hydrazines

Single Nucleotide‐Catalyzed Biomimetic Reductive Amination

Applications of N′-alkylated derivatives of TsDPEN in the asymmetric transfer hydrogenation of CO and CN bonds

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