Gennady Nisnevich

Efficient Synthesis of Secondary Alkyl Fluorides via Suzuki Cross-Coupling Reaction of 1-Halo-1-fluoroalkanes

Organofluorine compounds have found extensive applications in various areas of science. Consequently, the development of new efficient and selective methods for their synthesis is an important goal in organic chemistry. Here, we present the first Suzuki cross-coupling reaction which utilizes dihalo compounds for the preparation of secondary alkyl fluorides. Namely, an unprecedented use of simple 1-halo-1-fluoroalkanes as electrophiles in C(sp(3))-C(sp(3)) and C(sp(3))-C(sp(2)) cross-couplings allows for the formal site-selective incorporation of F-group in the alkyl chain with no adjacent activating functional groups. Highly effective approach to the electrophilic substrates, 1-halo-1-fluoroalkanes, via iododecarboxylation of the corresponding α-fluorocarboxylic acids is also presented. The conceptually new route to organofluorides was used for the facile preparation of biomedically valuable compounds. In addition, we demonstrated that an asymmetric version of the developed reaction for the stereoconvergent synthesis of chiral secondary alkyl fluorides is feasible.

Stereo- and regioselectivity in asymmetric synthesis of α-amino substituted benzocyclic compounds

Abstract The enantiomerically pure chiral benzocyclic amines 6 – 8 were obtained by asymmetric transamination of the corresponding prochiral ketones 9a – c . The method involves: (a) formation of chiral imines 10a – c from the prochiral ketones 9a – c and the inexpensive chiral auxiliary ( R )- or ( S )-phenylethylamine (PEA); (b) asymmetrically induced reduction of these imines to the diastereomeric amines 11a – c and 12a – c ; (c) catalytic hydrogenation to remove the benzylic fragment of the chiral PEA auxiliary. The stereoselectivity of the imine reduction, as well as the regioselectivity of the catalytic hydrogenation, are strongly dependent on the size of the saturated ring condensed with the benzene ring. This approach was used to develop a convenient, high yielding, and stereoselective route to several practically important optically active α-amino substituted benzocyclic compounds.

Coordination chemistry of N-heterocyclic nitrenium-based ligands.

Comprehensive studies on the coordination properties of tridentate nitrenium-based ligands are presented. N-heterocyclic nitrenium ions demonstrate general and versatile binding abilities to various transition metals, as exemplified by the synthesis and characterization of Rh(I) , Rh(III) , Mo(0) , Ru(0) , Ru(II) , Pd(II) , Pt(II) , Pt(IV) , and Ag(I) complexes based on these unusual ligands. Formation of nitrenium-metal bonds is unambiguously confirmed both in solution by selective (15) N-labeling experiments and in the solid state by X-ray crystallography. The generality of N-heterocyclic nitrenium as a ligand is also validated by a systematic DFT study of its affinity towards all second-row transition and post-transition metals (Y-Cd) in terms of the corresponding bond-dissociation energies.

Aliphatic C–H Bond Iodination by a N-Iodoamide and Isolation of an Elusive N-Amidyl Radical

Contrary to C-H chlorination and bromination, the direct iodination of alkanes represents a great challenge. We reveal a new N-iodoamide that is capable of a direct and efficient C-H bond iodination of various cyclic and acyclic alkanes providing iodoalkanes in good yields. This is the first use of N-iodoamide for C-H bond iodination. The method also works well for benzylic C-H bonds, thereby constituting the missing version of the Wohl-Ziegler iodination reaction. Mechanistic details were elucidated by DFT computations, and the N-centered radical derived from the used N-iodoamide, which is the key intermediate in this process, was matrix-isolated in a solid argon matrix and characterized by UV-vis as well as IR spectroscopy.

CCDC 983138: Experimental Crystal Structure Determination

Related Article: Yuri Tulchinsky, Sebastian Kozuch, Prasenjit Saha, Assaf Mauda, Gennady Nisnevich, Mark Botoshansky, Linda J. W. Shimon, Mark Gandelman|2015|Chem.-Eur.J.|21|7099|doi:10.1002/chem.201405526