Indirect and direct catalytic asymmetric reductive amination of 2-tetralone

Herein we report a one-pot catalytic asymmetric reductive amination of 2-tetralone. High-throughput screening of a small library of chiral ligands allowed us to perform the enantioselective hydrogenation of the intermediate enamine with up to 60% ee and a one-pot reaction with up to 47% enantiomeric excess of the desired amine.     

Primordial reductive amination revisited

Amino acids are formed efficiently by reductive amination of α-keto acids under aqueous, conditions with freshly precipitated FeS or Fe(OH)₂ and with NH₃, CH₃NH₂ or (CH₃)₂NH at pH values near their pK_a.     

Enantioselective organocatalytic reductive amination

The first enantioselective organocatalytic reductive amination reaction has been accomplished. The development of a new chiral phosphoric acid catalyst has provided a convenient strategy for the enantioselective construction of protected primary amines and provided a highly stereoselective method for the reductive amination of heterocyclic amines. A diverse spectrum of ketone and amine substrates can be accommodated in high yield and excellent enantioselectivity. This new protocol realizes a key benefit of reductive amination versus imine reduction, in that ketimines derived from alkyl-alkyl ketones are unstable to isolation, a fundamental limitation that is comprehensively bypassed using this direct organocatalytic reductive amination.     

Direct reductive amination using triethylsilane and catalytic bismuth(III) chloride

Direct reductive amination (DRA) using triethylsilane (TESH) and catalytic bismuth(III) chloride (BiCl₃) is described for the first time. The use of TESH and BiCl₃ provides easy handling, low cost, non-toxicity, and a mild Lewis acid activity, thereby meeting the demand for green and sustainable chemistry. The developed DRA is highly chemoselective and applicable to less-basic amines. The experimental results of this study revealed that the developed DRA could be catalyzed by BiCl₃, which was gradually reduced to Bi(0) or bismuth with a low valency by TESH, but TESCl, Bi(0), and Bi(0) with TESCl catalyzed the DRA to some extent.     

Single-step thioetherification by indium-catalyzed reductive coupling of carboxylic acids with thiols

Direct thioetherification from a variety of aromatic carboxylic acids and thiols using a reducing system combined with InBr(3) and 1,1,3,3-teramethyldisiloxane (TMDS) in a one-pot procedure is demonstrated. It was also found that a system combined with InI(3) and TMDS underwent thioetherification of aliphatic carboxylic acids with thiols.     

The reductive amination of aldehydes and ketones by catalytic use of dibutylchlorotin hydride complex

The reductive amination of aldehydes or ketones using Ph(2)SiH(2) or PhSiH(3) has been effectively promoted by the direct use of Bu(2)SnClH-pyridine N-oxide as a catalyst; this method has advantages in terms of its mild conditions and wide application to various carbonyls and amines, including aliphatic examples.     

Synthesis of Fmoc-protected aza-β-amino acids via reductive amination of glyoxylic acid

The reductive amination of glyoxylic acid, with a protected Fmoc hydrazine, has been developed as a simple and efficient method for the preparation of Fmoc-aza-β³-amino acid residues (aza-β³-aa). Anchoring on resin of these residues will be described as well as the synthesis of hybrid peptide.     

Cu(I)-mediated reductive amination of boronic acids with nitroso aromatics

[reaction: see text] A mild method for the reductive amination of aryl boronic acids with nitroso aromatic compounds is reported. This C-N bond formation is mediated by a stoichiometric amount of CuCl as both a catalyst and a reducing agent. Alternatively, 10% Cu(I)-3-methylsalicylate (CuMeSal) catalyzes the same reaction in the presence of either ascorbic acid or hydroquinone as the terminal reducing agent. Diarylamines bearing a variety of functional groups can be obtained in good yields.     

Functionalization of organotrifluoroborates: reductive amination

Herein we report the conversion of aldehyde-containing potassium and tetrabutylammonium organotrifluoroborates to the corresponding amines through reductive amination protocols. Potassium formate facilitated by catalytic palladium acetate, sodium triacetoxyborohydride, and pyridine borane have all served as effective hydride donors, reducing the initially formed imines or iminium ions to provide the corresponding amines.     

Catalytic Leuckart-Wallach-type reductive amination of ketones

A CpRh(III) complex catalyzes reductive amination of ketones using HCOONH(4) at 50-70 degrees C to give the corresponding primary amines in high yields. The reaction is clean and operationally simple and proceeds at a lower temperature and with higher chemoselectivity than the original Leuckart-Wallach reaction. The new method has been applied to the synthesis of alpha-amino acids directly from alpha-keto acids.     

A practical synthesis of enantiopure N-carbobenzyloxy-N′-phthaloyl-cis-1,2-cyclohexanediamine by asymmetric reductive amination and the Curtius rearrangement

Enantiomerically pure N-carbobenzyloxy-N′-phthaloyl-cis-1,2-cyclohexanediamine was synthesized by the asymmetric reduction of a β-enamino ester formed from benzyl 2-oxocyclohexanecarboxylate and (R)-phenylethylamine, followed by hydrogenolysis, phthaloylation, and the Curtius rearrangement.     

Ruthenium-catalyzed reductive amination of allylic alcohols

Straighforward access to various saturated amines from allylic alcohols and isostructural mixture can now be achieved in the presence of arene ruthenium catalyst featuring phosphinesulfonate ligand and a hydrogen donor.     

The first highly enantioselective homogeneously catalyzed asymmetric reductive amination: synthesis of alpha-N-benzylamino acids

High-throughput screening considering a library of 96 chiral P-ligands involved in two types of Rh(I) complexes was used for the identification of homogeneous catalysts for the highly enantioselective reductive amination of alpha-keto acids with benzylamine. After optimization of the reaction conditions and scale-up with a cationic Rh-Deguphos catalyst, a range of chiral alpha-amino acids could be produced by this new reaction in good yield and by up to 98% ee.     

General and practical conversion of aldehydes to homologated carboxylic acids

The reaction of aldehydes with trichloromethide followed by sodium borohydride or sodium phenylseleno(triethyl)borate under basic conditions affords homologated carboxylic acids in high yields. This operationally simple procedure provides a practical, efficient alternative to other homologation protocols. The approach is compatible with sensitive aldehydes including enals and enolizable aldehydes. It also offers convenient access to alpha-monodeuterated carboxylic acids.     

Intrastrand foldamer crosslinking by reductive amination

A series of m‐phenylene ethynylene (mPE) foldamers were crosslinked in their helical conformation using a reductive amination‐based strategy. This was accomplished by placing aldehyde moieties in the backbone of the oligomer at specific residues, which allowed a diamine crosslinker to covalently link the helical loops together. Three different foldamers with crosslinks placed at different locations in the backbone were synthesized and characterized by mass spectrometry, ¹H NMR, and gel permeation chromatography. The effect of the crosslinking on the stability of the folded state was evaluated through solvent denaturation studies. These studies show a reduction in the oligomer's ability to unfold of up to 30% relative to an unmodified mPE oligomer of the same length in solvents that promote unfolding. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 927–935, 2010