Reductive amination pyridine borane

Reductive amination of carbonyl compounds. Sodium cyanoborohydride has been the reductant of choice for this reaction, even though it is highly toxic (4, 448-449). Borane-pyridine is recommended as a nontoxic substitute. The reactions are conducted in acetic acid, in which this borane is fairly stable, and a co-solvent such as CH2CI2 or THE... 

Reductive amination with piperidines. Treatment of a piperidine and an aldehyde with the borane-pyridine complex gives the tertiary amine. 

Reductive amination Treatment of aldehydes or ketones with amines and the borane-pyridine complex in methanol in the presence of 4 A molecular sieves leads to secondary amines. 

Reductive amination, a suitable method for N-alkylation of amines, can be carried out using methanolic pyridine-borane under conventional conditions at room temperature for 3-16 h (95JOC5995). Under MWI, alkylation of hexahydroazepine 432 with paraformaldehyde and formic acid gave 70% of A -methylhexahydroazepine 433 after 4min of irradiation (Scheme 85) (01JCR(S)292). Similarly, A -alkyl and A -cycloalkylhydroazepines 434 and 435 were obtained in 28-81% yields. 

Y. Kikugawa. Chemistry of amine-boranes. Part 3. Reduction of tryptophan derivatives with pyridine-borane. J. Ghem. Research (5), 1978, 184. 

V. T. Perchyonok and Kellie L. Tuck of Monash University found (Tetrahedron Lett. 2008, 49, 4777) that a concentrated solution of Bu NCl and HjPOj in water effected free radical reductions and cyclizations. Stephane G. Ouellet of Merck Frosst demonstrated (Tetrahedron Lett. 2008, 49, 6707) that an oxazoline such as 3 could be converted to the alcohol 4 by acylation followed by reduction. Elizabeth R. Burkhardt of BASF developed (Tetrahedron I tt. 2008, 49, 5152) a protocol for scalable reductive amination using an easily metered liquid pyridine-borane complex. Mohammad Movassaghi of MIT devised (Angew. Chem. Int Ed. 2008, 47, 8909) a strategy for conversion of an allyUc carbonate 8 by way of the ally lie diazene to the terminal alkene 9. 

The desired pyridylamine was obtained in 69 % overall yield by monomethylation of 2-(aminomethyl)pyridine following a literature procedure (Scheme 4.14). First amine 4.48 was converted into formamide 4.49, through reaction with the in situ prepared mixed anhydride of acetic acid and formic acid. Reduction of 4.49 with borane dimethyl sulfide complex produced diamine 4.50. This compound could be used successfully in the Mannich reaction with 4.39, affording crude 4.51 in 92 % yield (Scheme 4.15). Analogous to 4.44, 4.51 also coordinates to copper(II) in water, as indicated by a shift of the UV-absorption maximum from 296 nm to 308 nm. 

REDUCTION, REAGENTS Bis(N-methylpi-perazinyl)aluminum hydride. Borane-Di-methyl sulfide. Borane-Tetrahydrofurane. Borane-Pyridine. n-Butyllithium-Diisobu-tylaluminum hydride. Calcium-Amines. Diisobutylaluminum hydride. 8-Hydroxy-quinolinedihydroboronite. Lithium aluminum hydride. Lithium 9-boratabicy-clo[3.3.1]nonane. Lithium n-butyldiisopro-pylaluminum hydride. Lithium tri-j c-butylborohydride. Lithium triethylborohy-dride. Monochloroalane. Nickel boride. 2-Phenylbenzothiazoline. Potassium 9-(2,3-dimethyl-2-butoxy)-9-boratabicy-clo[3.3.1]nonane. Raney nickel. Sodium bis(2-methoxyethoxy)aluminum hydride. Sodium borohydride. Sodium borohy-dride-Nickel chloride. Sodium borohy-dride-Praeseodymium chloride. So-dium(dimethylamino)borohydride. Sodium hydrogen telluride. Thexyl chloroborane-Dimethyl sulfide. Tri-n-butylphosphine-Diphenyl disulfide. Tri-n-butyltin hydride. Zinc-l,2-Dibromoethane. Zinc borohydride. 

REDUCTION, REAGENTS Bis(triphenyl-phosphine)copper tetrahydroborate. Borane-Pyridine. Calcium-Methylamine/ ethylenediaminc. Chlorobis(cyclopenta-dienyl)tetrahydroboratozirconium(IV). Chromium(II)-Amine complexes. Copper(0)-lsonitrile complexes. 2,2-Dihydroxy-l, 1-binaphthyl-Lithium aluminum hydride. Di-iododimethylsilane. Diisobutyl-aluminum 2,6-di-/-butylphenoxide. Diisobutyl aluminum hydride. Dimethyl sulfide-Trifluoroacetic anhydride. Disodium tetracarbonylferrate. Lithium-Ammonia. Lithium-Ethylenediamine. Lithium bronze. Lithium aluminum hydride. Lithium triethylborohydride. Potassium-Graphite. 1,3-Propanedithiol. Pyridine-Sulfur trioxide complex. 

Reductions. iyn-Selective reduction of observed with borane-pyridine in the present predominate in the reduction with LiBHEt-.-C (Ph,P)4Pd catalyzes removal of the R SC the transformation of y,8-epoxy-o(,p-un.saiurj lers by the borane-dimethylamine complex Allyl group scavengers. In the solid-nitrogen by an (V-allyloxycarbonyl group can the presence of a borane-amine complex. 

Pyridine-substituted nicotines, nornicotines, and anabasines are available from a-cyano-amines by a new synthesis. The syntheses of ( )-[l - N]nornicotine and ( )-[l - N]nicotine have been described, from cyclopropyl 3-pyridyl ketone and [ N]formamide. 4-Methylnicotine has been prepared it shows no nicotine-like pharmacological activity. " An investigation into the stereochemical factors involved in the behaviour of nicotine and related compounds in the Menschutkin reaction has been conducted.A bridged nicotine , 1,2,3,5,6,10b-hexahydropyrido[2,3-g]indolizine (44), has been synthesized by carboxylation of the dilithium derivative of 2-methylnornicotine followed by cyclisation and reduction with borane in tetrahydrofuran. Several 5-halogeno-nicotines have been prepared and their pK values and biological activities measured. ... 

A general method of obtaining tertiary amine or pyridine complexes of organo-substituted boranes has been developed 172) which avoids the previous necessity of preparing intermediate alkylated diboranes in a separate step 61,66). This relatively new route involves reduction of an appropriately substituted boronate or borinate (or boroxine) with lithium aluminum hydride in the presence of the desired amine 66, 74, 129,173, 174). 

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