Enantioselective Michael addition to vinyl phosphonates via hydrogen bond-enhanced halogen bond catalysis.

An asymmetric Michael addition of malononitrile to vinyl phosphonates was accomplished by hydrogen bond-enhanced bifunctional halogen bond (XB) catalysis. NMR titration experiments were used to demonstrate that halogen bonding, with the support of hydrogen-bonding, played a key role in the activation of the Michael acceptors through the phosphonate group. This is the first example of the use of XBs for the activation of organophosphorus compounds in synthesis. In addition, the iodo-perfluorophenyl group proved to be a better directing unit than different iodo- and nitro-substituted phenyl groups. The developed approach afforded products with up to excellent yields and diastereoselectivities and up to good enantioselectivities.

[2,3]-Wittig Rearrangement as a Formal Asymmetric Alkylation of α-Branched Ketones.

The enantioselective [2,3]-Wittig rearrangement of cinnamyloxycyclopentanone derivatives was performed in the presence of a Cinchona-based primary amine. The described method provides synthetically valuable α-hydroxy ketones with quaternary stereogenic centers in excellent enantiomeric purities. Relying on the X-ray crystal structure of the product and the DFT calculations, we propose that the rearrangement is promoted by an intramolecular hydrogen bond between the substrate and the catalyst.

Halo-1,2,3-triazolium Salts as Halogen Bond Donors for the Activation of Imines in Dihydropyridinone Synthesis.

In the past decade halogen bond (XB) catalysis has gained considerable attention. Halo-triazoles are known XB donors, yet few examples detail their use as catalysts. As a continuation of our previous work the catalytic properties of substituted enantiomerically pure halo-triazolium salts were explored in the reaction between an imine and Danishefsky's diene leading to the formation of dihydropyridinone. The catalytic activity of the XB donors was highly dependent on the choice of the halogen atom and on the counterion. Also, it was found that impurities in the diene affected the rate of the reaction.

Tunable chiral triazole-based halogen bond donors: assessment of donor strength in solution with nitrogen-containing acceptors.

Strong halogen bond (XB) donors are needed for the activation of neutral substrates. We demonstrate that XB donor properties of iodo-triazoles can be significantly enhanced by quaternization in combination with varying the counterion and aromatic substituent, exemplified by association constants with quinuclidine as high as 1.1 × 104 M-1.

An NMR and MD modeling insight into nucleation of 1,2-alkanediols: selective crystallization of lipase-catalytically resolved enantiomers from the reaction mixtures.

The work on developing a scalable lipase-catalytic method for the kinetic resolution of long-chain 1,2-alkanediols, complemented by crystallization of the pure enantiomers from the reaction mixtures, offered the possibility of a more detailed study of the aggregation of such diols. MD modeling, mass spectrometry, (1)H NMR, and DOSY studies provided a novel insight into the nucleation process. An efficient protocol for stereo- and chemoselective crystallization of (S)-1,2-dodecanediol and related compounds from the crude bioconversion mixtures was developed.

Enantioselective Henry reaction catalyzed by Cu(II) salt and bipiperidine.

A complex derived from the enantiomeric bipiperidine and copper(II) acetate hydrate is an efficient catalyst for the enantioselective Henry reaction. The easy availability of both catalyst components, mild reaction conditions, high yield, and good to excellent enantioselectivity make the catalyst useful for everyday practice.

Synthesis of deoxy sugar esters: a chemoenzymatic stereoselective approach affording deoxy sugar derivatives also in the form of aldehyde.

A chemoenzymatic synthesis of deoxy sugar esters is described. The synthesis is based on the O-alkylation of carboxylic acid with 2-bromo-5-acetoxypentanal. The method allows treatment of hydroxy carboxylic acids without protection of alcoholic hydroxyl groups. Several stereoisomeric deoxy sugar esters were resolved (up to ee or de > 98%) using a lipase-catalyzed acetylation of hemiacetals that in certain cases afforded deoxy sugar derivatives in the form of aldehydes. The stereochemistry of the reactions was determined by the NMR spectra of mandelic acid derivatives.