Efficient lipase-catalyzed enantioselective desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols and meso 1,2-diols using 1-ethoxyvinyl 2-furoate.

An efficient lipase-catalyzed desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols was developed using 1-ethoxyvinyl 2-furoate 1b, for which the well-known method using vinyl or isopropenyl acetate has had limited success due to low reactivity and easy racemization of the products through acyl group migration. The reagent 1b is highly reactive and converts various prochiral 1,3-diols to the monoesters having a chiral quaternary carbon center with 82-99% ee. These products were stable against racemization under acidic conditions, and their furoyl groups were compatible with oxidative conditions. Prolonging the reaction time led to the kinetic resolution of the monoesters resulting in an increase of their optical purity. The similar desymmetrization of meso cis-1,2-cycloalkanediols gave the monoesters with 82-97% ee without racemization.     

Ruthenium- and lipase-catalyzed DYKAT of 1,2-diols: an enantioselective synthesis of syn-1,2-diacetates

Regio- and stereoselective lipase-catalyzed kinetic resolutions were investigated for some unsymmetrical, secondary/secondary syn-diols. Candida antarctica lipase B-catalyzed transesterifications of a few aryl/alkyl- and alkyl/alkyl 1,2-diols were coupled in one-pot for efficient ruthenium-catalyzed epimerization and intramolecular acyl migration to give a dynamic kinetic asymmetric transformation (DYKAT) affording enantioenriched (ee up to >99%) syn-diacetates as the main diastereomers (syn:anti ∼2:1 to 10:1).     

C(2)-Symmetric bis-sulfoxide: A novel chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols

A new heterocyclic compound, C(2)-symmetric bis-sulfoxide 1, has been found to be an efficient chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols via diastereoselective acetal fission. Both (R,R)- and (S,S)-1 are readily synthesized with high optical purity via asymmetric oxidation of 1, 5-benzodithiepan-3-one (2). After acetalization of meso-1,2-diols 6a-e and a mono-TMS ether 6f with this chiral auxiliary 1, the resulting acetals 7a-f were subjected to base-promoted acetal fission upon treatment with potassium hexamethyldisilazide (KHMDS) followed by acetylation or benzylation to give the desymmetrized diol derivatives 8a-f with high diastereoselectivity. The chiral auxiliary 1 is readily removed by acid-promoted hydrolysis and can be recovered without a loss in enantiomeric excess.     

Synthesis of cyclopropene alpha-amino acids via enantioselective desymmetrization

[reaction: see text] The preparation of cyclopropene alpha-amino acids via the enantioselective desymmetrization of cyclopropene bis-carboxylic acid derivatives is described. The amino acids are stable to harsh reaction conditions, and a derivative has been incorporated into a tripeptide using conventional methods for peptide synthesis.     

Asymmetric synthesis of novel spirocycles via a chiral phosphoric acid catalyzed desymmetrization

A straightforward method for the asymmetric preparation of novel lactone and lactam spirocycles is described. An initial desymmetrization via a chiral Brønsted acid yields enantioenriched lactones which readily undergo a second cyclization to give the desired spirocycle.     

Scandium-bipyridine-catalyzed enantioselective aminolysis of meso-epoxides

The scandium-bipyridine-catalyzed enantioselective addition of anilines and O-alkyl hydroxylamines to meso-epoxides has been optimized and extended to a broad range of epoxides and amines. Whereas aromatic meso-epoxides generally furnished the corresponding 1,2-amino alcohols in excellent enantioselectivities, aliphatic meso-epoxides only gave rise to moderate enantioselectivities in the aminolysis. The catalyst loading may be lowered to just 5 mol% with only marginal effects on yield and enantioselectivity. A strong positive nonlinear effect has been observed, pointing to aggregation phenomena of the catalyst.     

Indium-bipyridine-catalyzed, enantioselective thiolysis of meso-epoxides

The indium-bipyridine-catalyzed, enantioselective ring-opening of meso-epoxides with aliphatic and aromatic thiols furnished 1,2-mercapto alcohols in good yields and excellent enantioselectivities; the crystal structure of the chiral catalyst reveals a pentagonal-bipyramidal coordination geometry around the indium center.     

An efficient synthesis of chiral homophenylalanine derivatives via enantioselective hydrogenation

Chiral homophenylalanine derivatives were synthesized via enantioselective hydrogenation of 5a and 5b catalyzed by rhodium complexes bearing chiral phosphine and phosphinite legands. Enantiomeric excesses up to 96.2% were achieved when S-spiroOP(S-1) was used as a chiral ligand under 500 psi of H₂ pressure in acetone.     

Development of the enantioselective addition of ethyl diazoacetate to aldehydes: asymmetric synthesis of 1,2-diols

A novel synthetic strategy toward the asymmetric synthesis of vicinal diols bearing a tertiary center is presented. The method encompasses the dinuclear Mg-catalyzed asymmetric addition of ethyl diazoacetate into several aldehydes, oxidation of the diazo functionality, and diastereoselective alkyl transfer of various organometallics into the resulting chiral β-hydroxy-α-ketoesters to afford a diverse range of 1,2-diols in high yield, diastereoselectivity, and chirality transfer.     

Asymmetric synthesis of chiral glutaric acid derivatives via Rh-catalyzed enantioselective hydrogenation

The first Rh-catalyzed enantioselective hydrogenation of dimethyl 2-methyleneglutarate and its derivatives has been reported. For the hydrogenation of dimethyl 2-methyleneglutarate with a chiral ferrocene-based monodentate phosphoramidite ligand (FAPhos), good enantioselectivity (over 90% ee) with full conversions was achieved. In contrast, the hydrogenation of substrates bearing an aryl substituent at a methylene moiety proved to be more difficult, in which the best enantioselectivity of up to 81% ee was obtained by the use of a P-stereogenic BoPhoz-type ligand.     

Synthesis of 2-alkylidene-cycloalkane-1,3-diols via enantioselective intramolecular carbolithiation

The lithiodestannylation and intramolecular anti-selective carbolithiation of α-lithiated ω-carbamoyloxy-1-alkynyl carbamates have been used to synthesize highly enantioenriched protected 2-alkylidene-cycloalkane-1,3-diols.     

Enantioselective synthesis of lobeline via nonenzymatic desymmetrization

Lobeline has been prepared in enantiopure form via desymmetrization of lobelanidine with use of BTM, a nonenzymatic enantioselective acyl transfer catalyst.     

Guanidine-catalyzed enantioselective desymmetrization of meso-aziridines

An amino-indanol derived chiral guanidine was developed as an efficient Br?nsted base catalyst for the desymmetrization of meso-aziridines with both thiols and carbamodithioic acids as nucleophiles, which provided 1,2-difunctionalized ring-opened products in high yields and enantioselectivities.     

Chemoenzymatic synthesis of enantiomerically pure terminal 1,2-diols

A new practical method for the enzymatic synthesis of 1,2-diols has been developed by employing a lipase catalyzed one-pot transesterification protocol. A series of substituted -acetoxyphenylethanones 3a–g have been reduced to the corresponding alcohols under mild conditions employing sodium borohydride and moist neutral alumina, and further subjected for lipase catalyzed irreversible transesterification in the same pot to give mono- and diacetate diols (R)-4 and (S)-5, which on hydrolysis afforded terminal 1,2-diols, (R)- and (S)-6 in high enantiomeric excess.     

Truncated Cinchona alkaloids as catalysts in enantioselective monobenzoylation of meso-1,2-diols

Readily synthesised quincorine and quincoridine derived chiral diamines efficiently catalyse the asymmetric monobenzoylation of cyclic and acyclic meso-1,2-diols.     

The highly enantioselective Diels-Alder reaction of 1,2-dihydropyridine using chiral cationic palladium-phosphinooxazolidine catalyst for the synthesis of chiral isoquinuclidines

The enantioselective Diels-Alder reactions of 1-phenoxycarbonyl-1,2-dihydropyridine with 1-alkylated acryloyl-pyrazolidin-3-ones using chiral cationic palladium-phosphinooxazolidine (Pd-POZ) catalyst afforded chiral isoquinuclidines with excellent enantioselectivity (up to 97% ee).