Regio- and stereospecific syntheses of syn- and anti-1,2-imidazolylpropylamines from the reaction of 1,1'-carbonyldiimidazole with syn- and anti-1,2-amino alcohols

The regio- and stereospecific conversion of syn- and anti-1,2-amino alcohols to their respective syn- and anti-1,2-imidazolylpropylamines via treatment with 1,1'-carbonyldiimidazole is described. The rationale behind the regio- and stereospecific nature as well as the generality of the reaction is discussed.     

Synthesis of enantiomerically pure anti-1,2-diaryl and syn-1,2-alkylaryl vic-selenoamines

Phenylselenyl benzylcarbanion stabilized by an (S)-2-p-tolylsulfinyl group evolves in a highly stereoselective way in the reactions with (S)-N-(p-tolylsulfinyl)imines at -98 °C affording diastereomerically pure 1,2-selenoamino derivatives in good yields. The syn or anti relationship of the obtained compounds depends on the alkyl or aryl character of the imine. They are easily transformed into enantiomerically pure (1R,2S)-1-aryl[or (1S,2S)-1-alkyl]-2-(phenylseleno)-2-phenylethylamines by reaction with t-BuLi and subsequent methanolysis of the generated sulfinamide derivatives with TFA.     

Highly stereoselective syntheses of syn- and anti-1,2-amino alcohols

The reduction of N-protected amino ketones can be carried stereoselectively to produce either the syn- or anti-amino alcohol diastereomer. Carbamate-protected amino ketones can be reduced predictably and selectively to anti-amino alcohols with LiAlH(O-t-Bu)3 in ethanol at -78 degrees C. N-Trityl-protected amino ketones can be reduced selectively to syn-amino alcohols with LiAlH(O-t-Bu)3 in THF at -5 degrees C.     

New 1-amino-1,2-diphenylethanols as ligands for the enantioselective addition of alkyllithiums to benzaldehyde

In the presence of equimolar amounts of lithium alkoxides derived from N-substituted 2-amino-1,2-diphenyl-ethanols, alkyllithium reagents add to benzaldehyde to furnish optically active secondary alcohols with enantiomeric excesses of up to 86%. The best results were obtained using the N-isopropyl-N-methyl substituted amino-alcohol.     

A sequential enantioselective, organocatalytic route to chiral 1,2-oxazines and chiral pyridazines

A sequential, organocatalysed asymmetric reaction to access chiral 1,2-oxazines and chiral pyridazines is reported, which proceeds in moderate to good yields and good to excellent enantioselectivities.     

Enantioselective synthesis of syn- and anti-1,3-diols via allyltitanation of unprotected beta-hydroxyaldehydes

[reaction: see text] syn or anti-1,3-Diols units were synthesized with excellent diastereomeric excess from unprotected chiral beta-hydroxyaldehydes by using an enantioselective allyltitanation.     

A new route to 2-amino- or 2-hydroxy-3-pyridinecarboxylic acid derivatives

Schiff's bases derived from ketones and t-butylamine ( 1 ) reacted with methyl methoxymethylenemalonate to give 2-hydroxy-3-pyridinecarboxylates. Similarly, treatment of 1 with ethoxymethylenemalononitrile gave 2-amino-3-pyridinecarbonitriles. Compounds 1 on reaction with ethyl 2-cyano-3-ethoxypropenoate afforded 2-amino-3-pyridinecarboxylates.     

Asymmetric synthesis of trans-3-amino-4-alkylazetidin-2-ones from chiral N,N-dialkylhydrazones

Enantiopure N,N-dialkylhydrazones 3 smoothly react with N-benzyloxycarbonyl-N-benzyl glycine as an aminoketene precursor to afford trans-3-amino-4-alkylazetidin-2-ones 4 as single diasteromers. As an exception, hydrazone 3f (R = OBn) affords cis-(3R,4R)-4f under modified conditions. N-N Bond cleavage of cycloadducts 4 afforded free azetidinones 5 in high yields. [structure: see text]     

Facile synthesis of various substituted taurines,especially syn- and anti-1,2-disubstituted taurines,from nitroolefins

Taurine and substituted taurines present a group of important structural elements in many natural products. Various substituted taurines, including 1- and 2-substituted, 1,1-, syn-1,2-, and anti-1,2-disubstituted taurines, were synthesized from the corresponding nitroolefins via Michael addition with thioacetic acid, oxidation with peroxyformic acid, and the catalytic hydrogenation under the catalysis of palladium on carbon or platinum dioxide. It is a general, versatile, and salt-free method for the preparation of substituted taurines, especially for syn- and anti-1,2-disubstituted taurines and some taurines with more bulky substituents. The stereostructures of both syn- and anti-1,2-disubstituted taurines were deduced from the nitroalkyl thioacetates in the Michael addition, which were identified via the Karplus equation analysis and computational analysis, and finally confirmed by the XRD single crystal analysis. The diastereoselectivity in the Michael addition was rationalized with the Cram rule.     

Asymmetric reduction of azirines; a new route to chiral aziridines

The first enantioselective reduction of aromatic 2H-azirines yields aziridines in up to 70% ee, using the aminoalcohol-[RuCl2(p-cymene)]2 catalyzed asymmetric transfer hydrogenation reaction.     

Concise asymmetric synthesis of (+)-CP-99,994 and (+)-L-733,060 via efficient construction of homochiral syn-1,2-diamines and syn-1,2-amino alcohols

An efficient asymmetric synthesis of human NK-1 SP receptor antagonists (+)-CP-99,994 and (+)-L-733,060 was achieved starting from a common chiral intermediate (5). Our route featured the SmI2-induced reductive coupling of N-tert-butanesulfinyl imine (7) with aldehyde (6) as the key step as well as pivotal transformations of the anti-1,2-amino alcohol thus obtained to homochiral syn-1,2-amino alcohol and syn-1,2-diamine for the asymmetric synthesis of 2,3-disubstituted piperidines.     

A new and facile route for the synthesis of chiral 1,2-diamines and 2,3-diamino acids

The synthesis of chiral diamines and diamino acids has been achieved from the corresponding N-arylsulfonyl aziridines through reaction with a chiral isocyanate and subsequent hydrolysis of 2-imidazolidinones. The method appears to be general and of wide applicability.     

Synthetic route to chiral tetrahydroquinoxalines via ring-opening of activated aziridines

A highly regio- and stereoselective route for the synthesis of racemic and nonracemic tetrahydroquinoxalines via the S(N)2-type ring-opening of activated aziridines with 2-bromoanilines followed by the Pd-catalyzed intramolecular C-N bond formation is described.     

anti-1,2-Diols via Ni-catalyzed reductive coupling of alkynes and alpha-oxyaldehydes

[reaction: see text] Ni-catalyzed reductive coupling of aryl alkynes (1) and enantiomerically enriched alpha-oxyaldehydes (2) afford differentiated anti-1,2-diols (3) with high diastereoselectivity and regioselectivity, despite the fact that the methoxymethyl (MOM) and para-methoxybenzyl (PMB) protective groups typically favor syn-1,2-diol formation in carbonyl addition reactions of this family of aldehydes.     

A regio- and stereodivergent route to all isomers of vic-amino alcohols

Vicinal amino alcohols are substructures in several important natural products. They are also frequently employed ligands in asymmetric synthesis. Many enantioselective syntheses of vic-amino alcohols have been reported, but each structure has required its own synthetic route. This study presents a synthetic strategy leading to all eight possible isomers of a given beta-amino alcohol, starting from vinyl epoxides. The developed strategy focuses on the propensity of vinyl epoxides and vinylaziridines to be selectively ring-opened at the allylic position by suitable hard nucleophiles. Within this strategy, a novel large-scale aminolysis reaction and the synthesis of a trisubstituted N-H vinylaziridine are detailed.     

Catalytic dissymmetrization of meso-2-imidazolidinones: alternative route to chiral synthons for 1,2-diamines

The chiral functionalization of a simple heterocycle, 1,3-dihydro-2-imidazolone, was achieved by the highly enantioselective monodeacylation of meso-1,3-diacetyl-2-imidazolidinones via an oxazaborolidine-catalyzed borane reduction. This kinetically controlled dissymmetrization is sufficiently effective to provide a synthetic route to either enantiomer of (4S, 5S)- or (4R, 5R)-4,5-dimethoxy-2-imidazolidinone derivatives, which serve as chiral synthons for threo-1,2-diamines.     

Enantiopure trans-1-amino-2-(arylsulfanyl)cyclohexanes: novel chiral motifs for ligands and organocatalysts

In order to obtain the title compounds (1R,2R)-cyclohexane-1,2-diol was stereoselectively converted into cis-(1R,2S)-2-(arylsulfanyl)cyclohexanols and these products were submitted to the nucleophilic substitution via the Mitsunobu reaction (HN₃, DEAD). Reduction of the isolated azides gave the desired trans-(1S,2S)-1-amino-2-(arylsulfanyl)cyclohexanes. The (1S,2S)-1-amino-2-(2-aminophenylsulfanyl)cyclohexanes thus prepared were reacted with 3,5-bis(trifluoromethyl)phenyl isothiocyanate to furnish the respective bis-thiourea compounds. An application of a derivative of this type as an organocatalyst (20 mol %) in the Baylis–Hillman reaction gave the respective product in up to 93% ee.     

Development and application of a new general method for the asymmetric synthesis of syn- and anti-1,3-amino alcohols

A general method is described for asymmetric synthesis of both syn- and anti-1,3-amino alcohols. The first application of metalloenamines derived from N-sulfinyl imines is reported for the highly diastereoselective addition to aldehydes. The reduction of the product beta-hydroxy N-sulfinyl imines 2 with catecholborane and LiBHEt(3) provides syn- and anti-1,3-amino alcohols with very high diastereomeric ratios. This method was found to be effective for a variety of substrates incorporating either aromatic or various aliphatic substituents. The convergent and efficient asymmetric syntheses of the two natural products, (-)-8-epihalosaline and (-)-halosaline, were also accomplished.     

A new convergent route to aldohexoses from a common chiral building block

[reaction in text] A diastereocontrolled route to the eight aldohexoses has been developed starting from a common cyclohexanoid chiral building block.