Highly enantioselective approach to geminal bisphosphonates by organocatalyzed Michael-type addition of beta-ketoesters

A valuable organocatalyzed protocol has been developed for the asymmetric synthesis of bisphosphonate derivatives, a class of pharmaceutically important molecules. Cheap and commercially available dihydroquinine effectively catalyzed conjugate additions of cyclic beta-ketoesters to ethylidenebisphosphonate esters, leading to optically active geminal bisphosphonates, bearing an all-carbon substituted quaternary stereocenter, in high yields and enantioselectivities of up to 99 % ee. Further elaborations of Michael adducts to the corresponding bisphosphonic acids or vinyl phosphonates have also been successfully performed, with conservation of optical purity.     

Regio‐ and Stereoselective Conjugate Addition of Aldehydes to β‐Tosyl Enones under the Catalysis of a Binaphthyl‐Modified Chiral Amine

A simple axially chiral amine catalyst promoted the regio‐, diastereo‐, and enantioselective conjugate addition of aldehydes to β‐tosyl enones, which serve as ynone surrogates. The adducts were readily converted by treatment with L‐selectride into less accessible enones with a γ stereogenic center. Such compounds cannot be prepared through the amine‐catalyzed conjugate addition of aldehydes to ynones. The obtained enones underwent further conjugate addition of diorganozinc compounds in the presence of a copper catalyst.     

Catalyst‐Controlled,Enantioselective, and Diastereodivergent Conjugate Addition of Aldehydes to Electron‐Deficient Olefins

A chiral‐amine‐catalyzed enantioselective and diastereodivergent method for aldehyde addition to electron‐deficient olefins is presented. Hydrogen bonding was used as a control element to achieve unusual anti selectivity, which was further elucidated through mechanistic and computational studies.     

Organocatalytic 1,4‐Addition Reaction of 2‐Formyl(thio)esters to Vinylketones: An Efficient Access to Acyclic Chiral Building Blocks with a Quaternary Carbon Stereocenter

2‐Formyl(thio)esters were utilized as pronucleophiles to obtain less‐accessible acyclic chiral building blocks bearing versatile functional groups on a quaternary carbon atom for enantioselective 1,4‐addition to vinylketones. To achieve high enantioselectivity in the present 1,4‐addition reaction, thiourea‐tertiary amines containing a bulky chiral backbone were developed as catalysts, and several derivatizations of the products were performed to demonstrate the synthetic utility of the products.     

Organocatalytic enantioselective synthesis of highly functionalized polysubstituted pyrrolidines

The organocatalytic conjugate addition of different aldehydes to beta-nitroacrolein dimethyl acetal, generating the corresponding highly functionalized nitroaldehydes in high yields and with high stereoselectivities, has been studied in detail. These transformations have been achieved by using both readily available starting materials in a 1:1 ratio as well as commercially available catalysts at a 10 mol % catalyst loading. Furthermore, a very short and efficient protocol has been devised for the preparation of highly enantioenriched pyrrolidines containing two or three contiguous stereocenters starting from the obtained Michael adducts. 3,4-Disubstituted pyrrolidines have been obtained in a single step by Zn-mediated chemoselective reduction of the nitro group followed by intramolecular reductive amination, and trisubstituted homoproline derivatives have been prepared by means of an olefination reaction and a cascade process involving chemoselective reduction of the nitro group followed by a fully diastereoselective intramolecular aza- Michael reaction.     

Enantioselective Organocatalytic Conjugate Addition of Aldehydes to Vinyl Sulfones and Vinyl Phosphonates as Challenging Michael Acceptors

Chiral framework : Chiral amines with pyrrolidine frameworks catalyze the enantioselective conjugate addition of a wide range of aldehydes to various vinyl sulfones and vinyl phosphonates in high yields and with enantioselectivities up to >99 % ee (see scheme). The high versatility of the Michael adducts is exemplified by various functionalizations with conservation of the optical purity.