C2-symmetric recyclable organocatalyst for enantioselective Strecker reaction for the synthesis of α-amino acid and chiral diamine--an intermediate for APN inhibitor

Recyclable chiral amide-based organocatalyst 5 efficiently catalyzed asymmetric Strecker reaction of various aromatic and aliphatic N-benzhydrylimines with ethyl cyanoformate as cyanide source at -10 °C to give a high yield (95%) of α-aminonitriles with excellent chiral induction (ee, up to 99%) with the added advantage of recyclability. Based on experimental observations a probable mechanism was proposed for this reaction. This protocol with catalyst 5 was extended for the synthesis of (R)-phenylalanine and pharmaceutically important drug intermediate (R)-3-phenylpropane-1,2-diamine in high yield with high enantioselectivity.     

Dehydroascorbic acid (DHAA) capped magnetite nanoparticles as an efficient magnetic organocatalyst for the one-pot synthesis of α-aminonitriles and α-aminophosphonates

A dehydroascorbic acid capped magnetite (DHAA-Fe₃O₄) catalyst is prepared and used for the one-pot synthesis of α-aminonitriles and α-aminophosphonates. Different derivatives of these compounds are synthesized in good yields.     

Diastereo- and enantioselective synthesis of anti-1,3-mercapto alcohols from α,β-unsaturated ketones via tandem Michael addition–MPV reduction

A new and effective asymmetric synthesis of anti-1,3-mercapto alcohols 3 from α,β-unsaturated ketones 1 utilizing tandem Michael addition–Meerwein–Ponndorf–Verley (MPV) reduction is described. Transformation of the MPV products anti-4 via the Wagner–Meerwein rearrangement was optimized under acidic or basic conditions to afford 1,3-mercapto alcohols anti-3, depending on the substituent R² of 4.     

Trifluoroethanol as a metal-free, homogeneous and recyclable medium for the efficient one-pot synthesis of α-amino nitriles and α-amino phosphonates

Trifluoroethanol is found to be an efficient and recyclable medium in promoting one-pot, three-component coupling reactions of aldehydes or ketones, amines and trimethylsilyl cyanide or trimethyl phosphite to afford the corresponding α-amino nitriles or α-amino phosphonates in high yields. This protocol does not require the use of an acid or base catalyst.     

Synthesis of rare earth catalysts and their applications for enantioselective synthesis of heterocyclic β-amino alcohols

A new family of chiral lanthanide complexes derived from (R)-binaphthol has been synthesized by a one-pot procedure using only commercially available substrates. These complexes were evaluated for the aminolysis of meso-epoxides and proved to be efficient enantioselective catalysts. The samarium complex coordinated by two (R)-binaphthoxide ligands was the most enantioselective catalyst of this series. β-Amino alcohols including heterocycles have been isolated with enantiomeric excesses up to 84%.     

Cinchona based squaramide catalysed enantioselective Michael addition of α-nitrophosphonates to aryl acrylates: enantioselective synthesis of quaternary α-aminophosphonates

Several cinchona based squaramide catalysts were applied to the asymmetric Michael addition of α-nitroethylphosphonates to acrylic acid aryl esters, resulting in high yields and enantioselectivities. The absolute configuration of one of the quaternary α-nitrophosphonate adducts was deduced from its experimental and calculated CD spectra. The adducts were reduced to their cyclic aminophosphonates by catalytic hydrogenation.     

Organocatalytic Michael addition of aldehydes to a β-silylmethylene malonate to form intermediates for the enantioselective synthesis of hydroxylated valerolactones and piperidines

The direct Michael addition of enolizable aldehydes to dimethyl(phenyl)silylmethylene malonate was catalysed by an (S)-diphenylprolinol trimethylsilyl ether/acetic acid combination. The adducts were formed in good yield, high diastereoselectivity and excellent enantioselectivity. Chiral valerolactone and piperidine skeletons embedded with a silyl and other functionalities have been made out of the adducts. A total synthesis (+)-simplactone B has been achieved from one of the adducts.     

Camphor-based oxazaphospholanes as chiral templates for the enantioselective synthesis of α-chlorophosphonic acids

Constrained camphor-derived oxazaphospholanes have provided an efficient entry for the preparation of enantiomerically enriched α-chlorophosphonic acids.     

BINOL-based azacrown ether catalyzed enantioselective Michael addition: asymmetric synthesis of α-aminophosphonates

Several novel 1,1′-bi-2-naphthyl-appended azacrown ethers with donor side-arms were synthesized and applied for the first time as chiral catalysts in the asymmetric Michael addition of an N-protected aminomethylenephosphonate onto acrylonitriles, resulting in high diastereoselectivity and enantioselectivity. The absolute configuration of the adduct was determined from its experimental and calculated CD spectra.     

Asymmetric synthesis of allylic secondary alcohols: a new general approach for the preparation of α-amino acids

A new general approach for the synthesis of optically active α-amino acids has been developed. The key steps involve a ruthenium catalysed cross-coupling reaction to give a range of α,β-unsaturated ketones, which were then reduced to allylic secondary alcohols in the presence of a chiral CBS oxazaborolidine. A thermal Overman rearrangement was used to prepare a series of allylic trichloroacetimidates and these were converted under standard conditions to the target α-amino acids in good overall yields.     

Brønsted acid catalyzed enantioselective α-amidoalkylation in the synthesis of isoindoloisoquinolines

The Parham cyclization-intermolecular α-amidoalkylation sequence results in the facile enantioselective synthesis of 12b-substituted isoindoloisoquinolines (ee up to 95%) using BINOL-derived Br?nsted acids. α-Amidoalkylation of indole occurs through the formation of a chiral conjugate base/bicyclic quaternary N-acyliminium ion pair.     

Diphenylparabanic acid as a synthon for the synthesis of α-diketones and α-ketocarboxylic acids

Diphenylparabanic acid was found to react with >2 equiv of organolithiums at -78 °C to effectively give the corresponding symmetrical α-diketones. However, upon treatment with 1 equiv of organolithium, the parabanic acid gave mainly 5-substituted 5-hydroxyimidazolidine-2,4-diones. On the other hand, Grignard reagents were less reactive toward the parabanic acid at low temperature, and selectively gave the corresponding 5-hydroxyimidazolidine-2,4-diones even if more than 1 equiv of the reagents was used. A tandem process in which the parabanic acid was first reacted with a Grignard reagent and then reacted in one-pot with an organolithium effectively gave the unsymmetrical α-diketone. 5-Substituted 5-hydroxyimidazolidine-2,4-diones were useful as versatile precursors for preparing α-ketocarboxylic acids as well as unsymmetrical α-diketones.     

A stereoselective synthesis of an α-substituted α-amino acid as a substructure for the construction of myriocin

A synthetic route to the protected quaternary α-amino acid 2 with a hydroxylated side chain has been achieved. The key transformations are the diastereoselective substrate-controlled epoxidation of allylic alcohol 4; a highly stereoselective oxidation–reduction protocol, and the excellent regioselective isomerization of the oxazolidinone ring to give an oxazinanone skeleton in derivative 3. The carboxylic acid 2 obtained represents the polar substructure, which is present in myriocin 1.     

Palladium-catalyzed cross-coupling of α-bromocarbonyls and allylic alcohols for the synthesis of α-aryl dicarbonyl compounds

The palladium-catalyzed coupling of olefins and organohalides is a versatile approach for synthesizing complex molecules from simple starting materials. We have developed a palladium-catalyzed coupling of α-bromocarbonyl compounds with allylic alcohols for the generation of acyclic aryl-substituted dicarbonyl compounds. The reaction proceeds via a tandem olefin insertion of an α-acyl radical followed by a 1,2-aryl migration. In addition to providing preliminary evidence for a free radical mediated mechanism, we demonstrate unprecedented levels of 1,3-stereoinduction for the 1,2-migration step.     

Rapid synthesis of highly functionalised α-amino amides and medium ring lactones using multicomponent reactions of amino alcohols and isocyanides

Four-component reactions between amino alcohols, aldehydes, isocyanides and thiols proceed rapidly under microwave or conventional heating at 60 °C in methanol. The reaction is successful with a wide range of components and gives access to potentially drug-like products containing amine, amide and thioether functionality in moderate to excellent yield. The reaction conditions are also applicable to the synthesis of a range of 8-10 membered medium ring lactones via three-component reactions of amino alcohols, isocyanides and acid-aldehydes. Incorporation of L-prolinol as the amino alcohol component in each case gives access to multicomponent products with moderate to high diastereoselectivity.     

Chiral azo compounds: enantioselective synthesis and transformations into β-amino alcohols and α-amino acids with a quaternary stereocenter

Taking advantage of radical carboaminations producing azo compounds, a new chemo-enzymatic approach to enantiomerically enriched azo alcohols, β-amino alcohols and non-natural (aromatic) amino acids with a quaternary stereocenter is reported.     

Highly enantioselective synthesis of α-fluoro-α-nitro esters via organocatalyzed asymmetric Michael addition

Primary amines catalyzed the asymmetric Michael addition of ethyl 2-fluoro-2-nitroacetate to enones to provide chiral α-fluoro-α-nitro ester ketones with two contiguous stereogenic centers, one of which is a fluorinated quaternary chiral center, with excellent enantioselectivities and in moderate to good yields.     

A facile and efficient synthesis of β-amino alcohols using 2,2,2-trifluoroethanol as a metal-free and reusable medium

Trifluoroethanol was used as a reusable catalyst and medium for the ring opening of epoxides using aliphatic and aromatic amines as nucleophile under mild conditions to give the corresponding β-amino alcohols in high yields and regioselectivity.     

A diastereo- and enantioselective Michael addition of chiral amide enolates to α, β-unsaturated esters a stereoelective synthesis of (+)-dehydroiridodiol and (−)-isodehydroiridodiol

(+)-Dehydroiridodiol and (−)-isodehydroiridodiol were synthesized stereoselectively using the diastereo- and enantioselective Michael addition of chiral amide enolates to α, β-unsaturated esters.