Enantioselective Amination of 3-Substituted-2-benzofuranones via Non-covalent N-Heterocyclic Carbene Catalysis.

Herein, an efficient method for asymmetric α-amination of 2-benzofuranones with N-heterocyclic carbene (NHC) catalysis is reported. The process is based on non-covalent interaction of NHC with substrate, facilitating the formation of a chiral ion-pair that encompasses enolate and azolium salt. The activated enolate adds to an electrophilic amine source with sufficient facial control to furnish an enantioenriched product having an amine substituted quaternary stereocenter. The process displays a broad substrate scope. A preparative scale synthesis has been achieved. Preliminary mechanistic investigations based on experimental and DFT studies suggest a reaction pathway that involves non-covalent substrate/NHC interactions and essentially implicate the role of π-π interaction in diastereomeric transition states for stereo-chemical discrimination.

Asymmetric Amination of meso-Epoxide with Vegetable Powder as a Low-Toxicity Catalyst.

This paper describes the scope and limitation of substrates subjected to asymmetric amination with epoxides catalyzed by a soluble soybean polysaccharide (Soyafibe S-DN), which we recently discovered from the reaction of 1,2-epoxycyclohexane with cyclopropylamine. Various meso-epoxides reacted with various amines afforded the corresponding products with good enantiomeric selectivity. Since it was found that pectin was found to have a catalytic ability after screening commercially available polysaccharides, we studied 33 different vegetable powders having pectic substances, and we found that many vegetable powders showed catalytic ability. These results should guide in using vegetable components as low-toxic catalysts for the production of pharmaceuticals.

Direct Alkylation of Amines with Primary and Secondary Alcohols through Biocatalytic Hydrogen Borrowing.

The reductive aminase from Aspergillus oryzae (AspRedAm) was combined with a single alcohol dehydrogenase (either metagenomic ADH-150, an ADH from Sphingobium yanoikuyae (SyADH), or a variant of the ADH from Thermoanaerobacter ethanolicus (TeSADH W110A)) in a redox-neutral cascade for the biocatalytic alkylation of amines using primary and secondary alcohols. Aliphatic and aromatic secondary amines were obtained in up to 99 % conversion, as well as chiral amines directly from the racemic alcohol precursors in up to >97 % ee, releasing water as the only byproduct.

Cooperative catalysis by palladium and a chiral phosphoric acid: enantioselective amination of racemic allylic alcohols.

Cooperative catalysis by [Pd(dba)2] and the chiral phosphoric acid BA1 in combination with the phosphoramidite ligand L8 enabled the efficient enantioselective amination of racemic allylic alcohols with a variety of functionalized amines. This catalytic protocol is highly regio- and stereoselective (up to e.r. 96:4) and furnishes valuable chiral amines in almost quantitative yield.

Construction of quaternary stereocenters: asymmetric α-amination of branched aldehydes catalyzed by monoimide substituted cyclohexane-1,2-diamines.

A highly efficient enantioselective α-amination of branched aldehydes catalyzed by chiral imide monosubstituted 1,2-diamine derivatives was reported to afford the quaternary stereogenic centers in excellent yields (up to 99%) and enantioselectivities (up to 97% ee). Chirality 25:668-672, 2013. © 2013 Wiley Periodicals, Inc.

Creation of a robust and R-selective ω-amine transaminase for the asymmetric synthesis of sitagliptin intermediate on a kilogram scale.

The creation of an R-selective ω-amine transaminase (ω-ATA) as biocatalyst is crucial for the asymmetric amination of prochiral ketones to produce sitagliptin intermediates because rare ω-ATAs are R-selective in nature and most of them suffer from poor stability and low activity toward bulky prochiral ketones. Here, the gene of an R-selective ω-ATA was cloned from Arthrobacter cumminsii ZJUT212 (AcATA) and expressed in Escherichia coli. The best variants (M1 + M122H and M1+T134 G) were obtained using a semi-rational protein design after screening. These variants not only exhibited improved activity and substrate affinity but also enhanced stability in aqueous phase containing 20 % dimethyl sulfoxide. The conversion of asymmetric amination on 50 g/L pro-sitagliptin ketone PTfpB (1-[1-piperidinyl]-4-[2,4,5-trifluorophenyl]-1,3-butanedione) achieved 92 %, with an extremely high e.e. of >99 %, using 2 gDCW/L E. coli cells harboring M1 + M122H as biocatalyst. In the kilogram-scale experiment, approximately 40 kg of (R)-APTfpB (e.e. >99 %) was produced within 30 h when 50 kg PTfpB was used as the substrate. Furthermore, the space-time yield reached ≈32 g/(L·d).

Diastereoselective synthesis of furanose and pyranose substituted glycine and alanine derivatives via proline-catalyzed asymmetric α-amination of aldehydes.

A concise organocatalytic route toward the synthesis of furanose and pyranose substituted glycine and alanine derivatives is reported. These compounds are core structural units of some of the naturally available antibiotics and antifungal agents. Proline-catalyzed asymmetric α-amination of aldehydes derived from sugars is used as the key reaction to synthesize twelve sugar amino acid derivatives. The asymmetric transformations proceeded in good yields and with good to excellent diastereoselectivity. The application of the synthesized amino acids is demonstrated by synthesizing a tripeptide containing one of them.