A facile method for the synthesis of enantiopure α-unsubstituted β-hydroxy esters

One-pot deacylation–debromination reactions involving the transesterification of the initial chiral α-bromo-β-hydroxy thioimide aldol adducts and subsequent Al–Hg mediated reductive cleavage of the C–Br bond allow for a facile synthesis of enantiopure β-hydroxy esters.     

Asymmetric synthesis of β-amino alcohols by the transfer hydrogenation of α-keto imines

The asymmetric transfer hydrogenation of representative aryl and benzofuranyl 2-tert-butylaminoethanones with formic acid–triethylamine, catalyzed by RhCl[(R,R)-TsDPEN](C₅Me₅), produced the corresponding β-tert-butylamino alcohols in 97–99% ee. A short asymmetric synthesis of (R)-bufuralol, a potent β-adrenergic receptor antagonist, is described. This approach to β-amino alcohols from ketones circumvents the halogenation–reduction–amination sequence.     

meta-Carborane-containing bismaleimides — New monomers for the synthesis of polyimides

The reaction of maleic anhydride with 1,7-bis(4,4-aminophenylamido)-m-carborane and 1,7-bis(4,4-aminophenylcarboxy)-m-carborane leads to the formation of the corresponding bis(maleamidocarboxylic acids) in quantitative yield. The subsequent dehydration of these compounds in a mixture of acetic anhydride and acetic acid in the presence of sodium acetate and triethylamine leads tom-carborane-containing bismaleimides, whose structure was indicated by IR spectroscopy. The chemical properties of these compounds were studied.A. N. Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 10, pp. 2446–2448, October, 1992.     

Chiral monofluorobenzyl carbanions: synthesis of enantiopure β-fluorinated β-phenylethylamines

The preparation of a stabilized monofluorobenzyl carbanion by means of a remote homochiral sulfinyl group and its completely stereoselective reactions with N-p-tolylsulfinylimines are described. The use of these reactions followed by the simultaneous removal of both chiral auxiliaries with tBuLi, which occurs without epimerization at the benzylic position, provides the quickest entry to enantiomerically pure β-fluorinated β-phenylethylamines.     

Aza-annulation of β-enaminolactones: application to the synthesis of enantiopure difunctionalized bicyclic lactams

Diastereoselective aza-annulation of seven-membered β-enaminolactones 2 gives access to bicyclic heterocyles 5. Fragmentation of molecule 5a with lithium methoxide affords cis or trans bicyclic lactams 8 with excellent stereoselectivities.     

Asymmetric synthesis of β-fluoroaryl-β-amino acids

The conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to a range of β-fluoroaryl-α,β-unsaturated esters gave the corresponding β-amino esters with high diastereoselectivity and in good isolated yields. Sequential treatment of the resultant β-fluoroaryl-β-amino esters under optimised hydrogenolysis conditions, followed by ester hydrolysis with 2.0 M aq HCl, provided access to a range of β-fluoroaryl-β-amino acids in good yield.     

A practical synthesis of enantiopure β-methyltryptophan ethyl ester for a preparation of diabetes drug

A practical synthesis of (2R,3S)- and (2S,3R)-β-methyltryptophan ethyl ester (β-MeTrp-OEt) has been developed. Racemic threo-β-MeTrp-OEt was diastereoselectively prepared via crystallization-induced diastereomer transformation (CIDT) of the α-nitro equivalent of β-MeTrp-OEt. The enantiomers were resolved via diastereomeric salt formation using a half equivalent of (R)-2-(4-hydroxyphenoxy)propionic acid. The process allowed a diabetes drug candidate N-[(1R,2S)-1-({5-[(dimethylamino)methyl]-2-ethoxyphenyl}aminocarbonyl)-2-(1H-indol-3-yl)propyl]-4-phenyl-1-piperidinecarboxamide to be prepared in good yield with high quality.     

New method for the synthesis of β-bromostyrenes

A new stereoselective method was developed for the synthesis of -bromostyrenes (E/Z > 5/1) starting from hydrazones of aromatic aldehydes and bromoform in the presence of CuCl.     

Stereoselective synthesis of α- and β-glycofuranosyl amides by traceless ligation of glycofuranosyl azides

A highly stereoselective synthesis of α- or β-glycofuranosyl amides based on the traceless Staudinger ligation of glycofuranosyl azides of the galacto, ribo, and arabino series with 2-diphenylphosphanyl-phenyl esters has been developed. Both α- and β-isomers can be obtained with excellent selectivity from a common, easily available precursor. The process does not depend on the anomeric configuration of the starting azide but appears to be controlled by the C2 configuration and by the protection/deprotection state of the substrates. A mechanistic interpretation of the results, supported by (31)P NMR experiments, is offered and merged with our previous mechanistic analysis of pyranosyl azide ligation reactions.     

Asymmetric nucleophilic monofluorobenzylation of carbonyl compounds: synthesis of enantiopure vic-fluorohydrins and α-fluorobenzylketones

Asymmetric nucleophilic monofluoroalkylation of a broad range of aldehydes with an α-fluoro-γ-sulfinylbenzyl carbanion takes place with complete control of the facial selectivity at the carbanion and good to high anti-diastereoselectivity to give easily separable mixtures of two optically pure 1,2-fluorohydrin derivatives (up to 24:1 anti/syn). Separation and removal of the p-tolylsulfinyl group with tBuLi provides enantiomerically pure anti-1,2-disubstituted-1,2-fluorohydrins, whereas α-fluorobenzylketones can be obtained by desulfinylation of the mixture followed by pyridinium chlorochromate oxidation (one-pot process).     

Enhancement of sortase A-mediated protein ligation by inducing a β-hairpin structure around the ligation site

A Staphylococcus aureus transpeptidase, sortase A (SrtA), catalyzes selective peptide/protein ligations that have been applied to cell imaging and protein engineering, while the ligations do not proceed to completion due to their reversibility. We successfully enhanced SrtA-mediated protein ligation through the formation of a β-hairpin around the ligation site.     

Methodology for the synthesis of mimetics of peptide β-turns

This letter describes a scenario which provides for the stereospecific introduction of both the amino and carboxyl termini portion of a designed β-turn mimetic.     

Enantio- and chemoselective bioreduction of β-keto nitriles by the fungus Curvularia lunata

The use of methanol as cosolvent allows the chemoselective reduction of aromatic β-keto nitriles by the fungus Curvularia lunata CECT 2130, yielding the corresponding (S)-β-hydroxy nitriles in a highly enantioselective way.     

A new method for the synthesis of β-halonitroalkanes

Summary A new method is elaborated for the synthesis of -chloronitroalkanes; it consists in the reaction of phosphorus pentachloride with acetals obtained by the addition of primary -nitro alcohols to vinyl alkyl ethers.     

Asymmetric synthesis of β-amino acids through application of chiral sulfoxide

This paper describes asymmetric synthesis of β-aminophenylpropionic acid through application of a homochiral sulfoxide auxiliary. High kinetically controlled (3R,2S,R_S)-diastereoselectivity (−60°C) is achieved during addition of the lithium enolate of tert-butyl (+)-(R)-p-toluenesulfinylacetate to substituted N-(benzylidene)toluene-4-sulfonamides 2a–2d. The reductive cleavage of adduct 3a with sodium amalgam yielded tert-butyl 3-(toluene-4-sulfonamido)-3-phenylpropionate 5a, which was subjected to ester hydrolysis and subsequent detosylation with sodium in liquid ammonia to yield (S)-β-aminophenylpropionic acid in good yield and high 91% e.e.     

Asymmetric synthesis of α-chiral ketones by the reduction of enones with baker's yeast

Baker's yeast-mediated asymmetric reduction of α,β-unsaturated ketones (enones) having a pyridyl ring affords the corresponding optically active α-substituted ketones (α-chiral ketones) with excellent stereoselectivity. The position of the heteroatom, as well as the bulk of the α-substituent, plays an important role in governing the stereoselectivity in the reduction of a carboncarbon double bond.     

An efficient method for the synthesis of enantiopure cis-α,β-epoxy acids

Enantiopure cis-α,β-epoxy acids were prepared via a modified Darzen's reaction employing the titanium-mediated bromination–aldolization of chiral acetate thioimide enolate.     

Three-component one-pot reaction for the synthesis of β-amide ketones

β-amide ketones were synthesised by a three-component one-pot reaction of phenylacetylene, aldehydes, and amides in anhydrous acetonitrile containing trifluoroacetic acid and acetic acid in the presence of AlCl₃ catalyst. The title compound structures were identified by ¹H NMR, ¹³C NMR, MS, and elemental analysis.     

An improved procedure for the preparation of β-thiohydroximates for glucosinolate synthesis

A novel and simple method is described for the synthesis of β-thiohydroximates from oximes and 2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranose, which are key intermediates in the synthesis of glucosinolates. The procedure involves the in situ formation of an oximyl chloride from the oxime, using inexpensive bleach, which is then reacted directly under basic conditions with the thioglucopyranose.     

Stereoselective synthesis of enantiopure analogues of (−)-cephalotaxine

The asymmetric total synthesis of three analogues of (?)-cephalotaxine with structural modification of the aromatic ring was achieved in 16 steps and acceptable overall yields. The procedure used was quite similar to that reported by our group for the total synthesis of (?)-cephalotaxine in 2004. The enantiopure spiranic compound 4 is a common intermediate on which various aromatic groups can be introduced. Unexpected and interesting different chemical behaviors were observed during these syntheses.