51018-28-1

The iridium-f-amphox-catalyzed asymmetric hydrogenation of racemic α-amino β-unfunctionalized ketones proceeds via a DKR (dynamic kinetic resolution) process for the construction of various chiral N,N-disubstituted α-amino β-unfunctionalized alcohols in quantitative yields with excellent enantioselectivities and diastereoselectivities (all products >99% ee and >99:1 dr, TON up to 100 000). Importantly, this catalytic asymmetric hydrogenation with a DKR process provided a highly efficient and powerful synthetic strategy for the preparation of key chiral intermediates of the preclinical antitumor agent (S,S)-R116010.

Ephedrine-derived bifunctional thioureas have been synthesized and applied as organocatalysts in Michael additions of 1,3-dicarbonyl compounds to nitroalkenes. Georg Thieme Verlag Stuttgart.

Heterobidentate sulfide-tertiary amine ligands incorporating 1,2-aminothioethers derived from ephedrine and pseudoephedrine have been prepared and used successfully in the palladium-catalysed asymmetric allylic substitution reaction, giving ees of up to 89 percent. The stereoelectronic effects operating in the reactions are discussed.

N-Methyl pseudoephedrine mediated dynamic resolution of α-bromo-α-alkyl esters in nucleophilic substitution reaction has been investigated. Best results are obtained when α-bromo-α-alkyl esters 1, 4 and 5 are allowed to equilibrate before the addition of nucleophile. This simple epimerization-substitution sequence provides a practical protocol for asymmetric syntheses of α-amino acid derivatives 2, 7 and 8 up to 98:2 enantiomeric ratio.

Oxazolidinones are obtained by the cyclization of mesylates derived from N-Boc-β-Aminoalcohols. Hydrolysis of the N-Boc-Oxazolidinones regenerates the protected aminoalcohols with inverted configuration at the hydroxy group. (C) 2000 Elsevier Science Ltd.

The reductive cleavage of cyclic aminol ethers to give N-alkylamino-derivatives in very high yields can be achieved using chlorotrimethylsilane in the presence of sodium cyanoborohydride: in the case of cyclic aminol ethers derived from formaldehyde the Eschweiler-Clarke reaction can be carried out in formic acid heated under reflux in the absence of formaldehyde.

Phenylphosphinic acid and dialkylsulfoxides are found to be alternative reagents for respectively the reducing reagent (formic acid) and the alkylating reagent (aldehyde) currently used for secondary amines N-alkylation. Primary amines do not react with this system, but phenylglycine is decarboxilated to benzylamine.

A variety of chiral auxiliaries R*OH were prepared and tested for levels of asymmetric induction control in the "Mukaiyama-aldol" reaction of chiral silyl ketene acetals.Structural features required for high levels of control are discussed.

Reduction of aldehydes and ketones with hydrosilanes proceeded in the presence of a catalytic amount of tetrabutylammonium fluoride or tris(diethylamino)sulfonium difluorotrimethylsilicate in aprotic polar solvents under mild conditions.A significant isotope effect (kH/kD = 1.50) was observed in competitive reduction of acetophenone with HSiMe2Ph and DSiMe2Ph.The reaction was of first order in the concentration of an aprotic polar solvent HMPA.Reduction of 2-methylcyclohexanone gave cis-2-methylcyclohexanol with selectivities up to 95percent.The kinetic and stereochemical results suggest that a hexavalent fluorosilicate - is involved. α-Alkoxy (acyloxy or dimethylamino) ketones were transformed to threo alcohols in high diastereoselectivities.The reduction was also applied to α-methyl-β-keto amides, RCOCH(MeCONR)2, to afford the corresponding threo alcohols in >98percent selectivity.The threo selectivity is explained in terms of the Felkin-Anh model in which interaction of carbonyl oxygen with a countercation is ideally suppressed.The threo-directed reduction was applied to (R)-1-phenyl-4-(2-tetrahydropyranyloxy)-1-penten-3-one and N-(2-benzoylpropanoyl)piperidine.The resulting threo alcohols were respectively converted into (2R,3S)-2,3-(cyclohexylidenedioxy)butanal, a key intermediate of daunosamine synthesis, and into a pharmacologically useful compound threo-N-(3-hydroxy-2-methyl-3-phenylpropyl)piperidine.

Treatment of (S)-(η6-N,N-dimethylamphetamine)Cr(CO)3, with n-butyllithium below -40 deg C gives a stable benzylic carbanion via loss of the pro-R-benzylic proton.Warming of this anion above -40 deg C gives (η6-E-β-methylstyrene)Cr(CO), via an ElcB type elimination wilhst trapping with an electrophile below -40 deg C gives benzylically functionalised amphetamines with overall retention of configuration.The use of oxodiperoxymolybdenum(pyridine)hexamtehylphosphoramide as the electrophile gives optically pure (1S,2S)-N-methylpseudoephedrine after decomplexation.

The reduction of aminoketones and aziridinoketones with zinc borohydride is highly stereoselective.The zinc atom is complexed only by nitrogen atoms of reduced molecules.There is no chelate formation with the participation of carbonyl groups.

The pro-R hydrogen of (+)-N,N-dimethylamphetamine chromium tricarbonyl can be stereospecifically substituted via sequential treatment with BunLi and an electrophile, with retention of configuration to give for example N-methylpseudoephedrine after decomplexation.