Highly Homogeneous Stereocontrolled Construction of Quaternary Hydroxyesters by Addition of Dimethylzinc to α‐Ketoesters Promoted by Chiral Perhydrobenzoxazines and B(OEt)3

A highly efficient enantioselective addition of Me₂Zn to α‐ketoesters, assisted by a chiral perhydro‐1,3‐benzoxazine ligand, is described. This novel catalytic system offers homogeneous elevated enantioselectivities in the preparation of α‐hydroxyesters that bear a quaternary stereocenter, with a minor dependence on electronic and steric effects when aromatic, heteroaromatic, or aliphatic α‐ketoesters are employed. The catalyst can be recovered and reused without loss of activity.     

Biotransformation of aromatic ketones and ketoesters with the non-conventional yeast Pichia glucozyma

The non-conventional yeast Pichia glucozyma CBS 5766 has been used for the biotransformation of different aromatic ketones and ketoesters. The growth and biotransformation conditions were optimised for the reduction of acetophenone and under optimised conditions, propiophenone, butyrophenone and valerophenone were reduced to the corresponding (S)-alcohols with high yields and enantioselectivity. Ketoreductase(s) of Pichia glucozyma showed high catalytic activities also towards aromatic β- and γ-ketoesters, being often competitive with esterase(s). These concurrent activities allowed for the preparation of hydroxyesters, hydroxyacids and lactones often in a very selective manner.     

Copper–Boxmi Complexes as Highly Enantioselective Catalysts for Electrophilic Trifluoromethylthiolations

The enantioselective trifluoromethylthiolation of β‐ketoesters using chiral copper–boxmi complexes as catalysts is reported. A number of α‐SCF₃‐substituted β‐ketoesters have been obtained with up to >99 % enantiomeric excess (ee), and the trifluoromethylthiolated products were then transformed diastereoselectively to α‐SCF₃‐β‐hydroxyesters with two adjacent quaternary stereocenters.     

An Unusual Triphenylphosphine Oxide Catalyzed Stereoselective 1,3‐Dichlorination of Unsaturated Ketoesters

An unusual Ph₃PO‐catalyzed stereoselective 1,3‐dicholorination of an unsaturated ketoester has been developed. The novel activation mode involved in this cascade reaction can promote consecutively elusive transformations. The products were obtained with good yields and excellent stereoselectivities. This reaction makes important complementation to the limitations associated with the field of dichlorination.     

Catalytic Asymmetric Intramolecular Homologation of Ketones with α‐Diazoesters: Synthesis of Cyclic α‐Aryl/Alkyl β‐Ketoesters

A catalytic asymmetric intramolecular homologation of simple ketones with α‐diazoesters was firstly accomplished with a chiral N,N′‐dioxide–Sc(OTf)₃ complex. This method provides an efficient access to chiral cyclic α‐aryl/alkyl β‐ketoesters containing an all‐carbon quaternary stereocenter. Under mild conditions, a variety of aryl‐ and alkyl‐substituted ketone groups reacted with α‐diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β‐ketoesters in high yield and enantiomeric excess.     

Transesterification of ketoesters with alcohols using polyaniline salts as catalysts

Polyaniline salts have been used as catalysts for the transesterification of ketoesters with alcohols in a process being reported for the first time. The catalytic use of polyaniline salts is feasible because of their easy preparation, recovery and reusability. Copyright © 2004 John Wiley & Sons, Ltd.     

Efficient Synthesis of Differentiated syn‐1,2‐Diol Derivatives by Asymmetric Transfer Hydrogenation–Dynamic Kinetic Resolution of α‐Alkoxy‐Substituted β‐Ketoesters

Asymmetric transfer hydrogenation was applied to a wide range of racemic aryl α‐alkoxy‐β‐ketoesters in the presence of well‐defined, commercially available, chiral catalyst Ru^II–(N‐p‐toluenesulfonyl‐1,2‐diphenylethylenediamine) and a 5:2 mixture of formic acid and triethylamine as the hydrogen source. Under these conditions, dynamic kinetic resolution was efficiently promoted to provide the corresponding syn α‐alkoxy‐β‐hydroxyesters derived from substituted aromatic and heteroaromatic aldehydes with a high level of diastereoselectivity (diastereomeric ratio (d.r.)>99:1) and an almost perfect enantioselectivity (enantiomeric excess (ee)>99 %). Additionally, after extensive screening of the reaction conditions, the use of Ru^II‐ and Rh^III‐tethered precatalysts extended this process to more‐challenging substrates that bore alkenyl‐, alkynyl‐, and alkyl substituents to provide the corresponding syn α‐alkoxy‐β‐hydroxyesters with excellent enantiocontrol (up to 99 % ee) and good to perfect diastereocontrol (d.r.>99:1). Lastly, the synthetic utility of the present protocol was demonstrated by application to the asymmetric synthesis of chiral ester ethyl (2S)‐2‐ethoxy‐3‐(4‐hydroxyphenyl)‐propanoate, which is an important pharmacophore in a number of peroxisome proliferator‐activated receptor α/γ dual agonist advanced drug candidates used for the treatment of type‐II diabetes.     

Catalytic asymmetric bromination and chlorination of beta-ketoesters

The first general catalytic asymmetric bromination and chlorination of beta-ketoesters has been developed. The reactions proceed for both acyclic and cyclic beta-ketoesters catalyzed by chiral bisoxazolinecopper(II) complexes giving the corresponding optically active alpha-bromo- and alpha-chloro-beta-ketoesters in high yields and moderate to good enantioselectivities. For the optically active chlorinated products the isolated yields are in the range of 88-99 % and the enantiomeric excesses up to 77 % ee, while the optically active brominated adducts are formed in 70-99 % isolated yield and up to 82 % ee. Based on the absolute configuration of the optically active products, the face selectivity for the catalytic enantioselective halogenation is discussed based on a bidentate coordination of the beta-ketoester to the chiral catalyst and a X-ray structure of chiral alpha,gamma-diketoesterenolatebisoxazolinecopper(II) complex.