A practical asymmetric synthesis of homochiral α-arylglycines

Enantioselective reduction of a series of substituted aryl trichloromethyl ketones with the CBS-catecholborane reagent afforded homochiral aryl trichloromethyl carbinols which have been elaborated to give homochiral α-arylglycines in high e.e.     

Asymmetric synthesis of α-acetylenic epoxides

Chiral α-acetylenic oxiranes were easily synthesized from readily available propargylic esters by a four-step sequence involving the stereoselective reduction of α′-alkynyl β-keto sulfoxides with DIBAH (de 66–78%) and DIBAH/ZnBr₂ (de 78–88%), followed by further reduction of the resulting hydroxy sulfoxides into the corresponding sulfenyl derivatives and final epoxy ring closure via sulfonium salt.     

Asymmetric synthesis of differentially protected α-alkyl succinates

The alkylation of the chiral iron acyls [(η⁵-C₅H₅)Fe(CO)(PPh₃)COCH₂R] (R = H, Me, n-Pr, n-Bu, i-Bu, n-C₅H₁₁) with t-butyl bromoacetate takes place highly stereoselectively to provide a series of novel iron succinoyl complexes, which on oxidative decomplexation lead directly to chiral α-alkyl succinates.     

Asymmetric synthesis of all isomers of α-methyl-β-phenylserine

This report describes the synthesis of enantiomerically pure (2R,3R)-, (2R,3S)-, (2S,3S)- and (2S,3R)-2-amino-3-hydroxy-2-methyl-3-phenylpropanoic acids, four quaternary α-amino acids, using a stereodivergent synthetic route and starting from (S)- and (R)-N-Boc-N,O-isopropylidene-α-methylserinals. The key step involves the asymmetric Grignard additions to the above chiral aldehydes, in which high levels of asymmetric induction are observed.     

Asymmetric synthesis of α,α-disubstituted α-amino alcohol derivatives

Herein we report the asymmetric synthesis of α,α-disubstituted α-amino alcohol derivatives 22, 25 and 26, key intermediates of a novel immunomodulator, using Seebach’s method. This synthetic method can be applied to the large scale synthesis of chiral sphingosine 1-phosphate-1 (S1P₁) receptor agonists, with significant improvements to the previously reported method with regard to the reaction temperature.     

Asymmetric synthesis of α-alkyl-α-hydroxy-γ-butyrolactones

A new enantioselective approach to α-alkyl-α-hydroxy-γ-butyrolactones employing (1R,2S)-ephedrine-derived chiral allyl morpholinones as starting materials is described.     

Asymmetric synthesis of β,β-difluoroamino acids via cross-coupling and Strecker reactions

β,β-Difluoroamino acids were synthesized from commercially available ethyl bromodifluoroacetate using cross-coupling and Strecker reactions as key steps. The coupling reaction of aryl iodides with ethyl bromodifluoroacetate gave the corresponding coupling products, which were transformed to 2-difluoromethyl-1,3-oxazolidines in two steps. Boron trifluoride etherate promoted Strecker reaction of 2-difluoromethyl-1,3-oxazolidines gave α-amino nitriles in good yields and diastereoselectivities. After removal of chiral auxiliary and hydrolysis of the nitrile group, β,β-difluorophenylalanine was obtained with 73% ee. Partial racemization occurred during the hydrolysis of nitrile group.     

Asymmetric synthesis of α-alkyl α-selenocarbonyl compounds catalyzed by bifunctional organocatalysts

A new organocatalytic approach for the synthesis of a variety of α-alkyl, α-phenylselenyl ketones as well as their corresponding esters and amides, by the addition of α-selenocarbonyl derivatives to nitroalkenes catalyzed by thiourea or squaramide cinchona catalysts, is presented. This catalytic system allows the preparation in high yields of enantiomerically enriched selenocarbonyl derivatives bearing two chiral centers with excellent ee's and dr's by using catalytic loadings of 3 mol%.     

Asymmetric synthesis of α-amino acids by reduction of N-tert-butanesulfinyl ketimine esters

A highly regio- and diastereoselective reduction of various N-tert-butanesulfinyl ketimine esters with L-Selectride resulting in the formation of α-amino acids is reported. This method is quite general and also practical for the preparation of both enantiomers of aryl or aliphatic α-amino acids in high yields.     

Highly diastereoselective Friedel-Crafts reaction of arenes with N-tert-butanesulfinylimino ester towards the efficient synthesis of α-arylglycines

Lewis acid-catalyzed highly diastereoselective asymmetric Friedel-Crafts alkylation of arenes with a chiral N-tert-butanesulfinylimino ester is described. The reaction can be accomplished with ease in the presence of a catalytic amount of In(OTf)(3) at room temperature, providing a series of enantiomerically enriched α-arylglycines in good yields and with excellent diastereoselectivities (up to 99% de). Highly stereoselective double Friedel-Crafts alkylation to afford dialkylation product was also investigated.     

Asymmetric synthesis of α-substituted alkylphosphonates based on symmetrical dialkyl phosphites

Chiral C₂-symmetrical dialkyl phosphites and C₃-symmetrical trialkyl phosphites, derived from (−)-borneol, (−)-menthol, and 1,2∶5,6-di-O-isopropylidene-α-d-glucofuranose, were studied as the starting reagents for the preparation of chiral organophosphorus compounds. The reactions of C₂-symmetrical dialkyl phosphites and C₃-symmetrical trialkyl phosphites with aldehydes and amines or aldehydes are accompanied by asymmetrical induction at the α-carbon atom to yield optically active α-aminoalkylphosphanates or α-hydroxyalkylphosphonates, respectively. The stereoselectivity of the reaction depends on the structure of the starting compounds and the reaction conditions. Translated fromIzvestiya Akademii, Nauk, Seriya Khimicheskaya, No. 8, pp. 1588–1593, August, 1999.     

Asymmetric synthesis of α-aryl amino acids; aryne-mediated diastereoselective arylation

An aryne-mediated α-arylation reaction of Scho?llkopf's bis-lactim ether is described. Arynes were generated via an ortho-lithiation approach, affording syn-arylated products in up to 94:6 dr with moderate to good yields and excellent regioselectivities. Hydrolysis provided a variety of substituted arylglycines containing a range of functional groups without racemization.     

Expeditious and efficient synthesis of Strecker’s α-aminonitriles catalyzed by sulfated polyborate

A straightforward, mild, efficient, and environmentally benign protocol for a three-component Strecker reaction of aldehydes or ketones, amines, and trimethylsilyl cyanide catalyzed by sulfated polyborate has been described to afford α-aminonitriles under solvent-free reaction conditions. The major advantages of the present method are excellent yields, shorter reaction time, simple experimental procedure, easy workup procedure, recyclability of the catalyst, solvent-free reaction conditions and ability to tolerate a variety of functional groups which gives economical as well as ecological rewards.     

Asymmetric Synthesis of α-Aminonitriles

The asymmetric synthesis of α-aminonitriles was carried out by the reaction of α-trimethylsilyloxynitriles with optically active α-methylbenzylamine in methanol. The reactions provided moderate yields and good optical purities.     

Asymmetric synthesis of α,β-substituted β-aminoalkanamides and stereochemical determination

Highly enantiomerically enriched β-aminoalkanamides 12 and β-phenylaminoalkanamides 13 have been prepared by the addition reaction of α-lithiated 2-alkyl-2-oxazolines 9-Li, derived from optically active oxazolines 9, to N-cumyl nitrones 2. The relative stereochemistry of alkanamides 5 and 6 has been established by 1D-NOESY experiments carried out on the related pyrimidinones 7, whereas the absolute configuration of alkanamides 12 and 13 has been confirmed by an X-ray analysis.     

Asymmetric synthesis of α-chloro-β-amino-N-sulfinyl imidates as chiral building blocks

New chiral α-chloro-β-amino-N-sulfinyl imidates were synthesized in high yield and excellent diastereomeric excess via highly anti-selective Mannich-type reactions of (R(S))-methyl N-tert-butanesulfinyl-2-chloroethanimidate with aromatic aldimines. The α-chloro-β-amino-N-sulfinylimidates proved to be excellent building blocks for the asymmetric synthesis of β-amino-α-chloro amides and esters, aziridine-2-carboxylic amides and esters, trans-2-aryl-3-chloroazetidines, and methyl 4-phenyloxazolidin-2-one-5-carboxylate. The obtained absolute anti-diastereoselectivity is the opposite of the stereochemical outcome observed for α-methyl-substituted imidates.     

Asymmetric total synthesis of (−)-rasfonin

An efficient chemoenzymatic asymmetric synthesis of pyranone containing natural product (?)-rasfonin is presented here. Enantioselective enzymatic desymmetrization (EED) and a unique Gluconobacter oxydans mediated oxidative kinetic resolution (OKR) have been successfully employed to install three stereocenters (C_6′, C₇, and C₉) of the target molecule. Stereoselective Achmatowicz reaction of a properly decorated furyl nucleus led to the core pyranone structure of rasfonin. At the late stage of the synthesis Negishi coupling has been used to complete the synthesis.     

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.     

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).