Difluorinated Danishefsky's diene: a versatile C(4) building block for the fluorinated six-membered rings.

[reaction: see text] A Mg(0)/Me(3)SiCl system was found to be effective for the preparation of difluoro Danishefsky's dienes 2, which involves selective C-F bond cleavage of trifluoromethyl ketones 3. Subsequent hetero Diels-Alder reactions of 2 with aldehydes and imines gave a variety of fluorinated six-membered heterocycles.

Pd-catalyzed asymmetric hydrogenation of alpha-fluorinated iminoesters in fluorinated alcohol: a new and catalytic enantioselective synthesis of fluoro alpha-amino acid derivatives.

[figure: see text] Under hydrogen pressure, a catalytic amount of palladium(II) trifluoroacetate and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) promoted asymmetric hydrogenation of alpha-fluorinated iminoesters to afford highly enantioenriched beta-fluorinated alpha-amino esters. The yield and ee were much improved by employing fluorinated alcohols such as 2,2,2-trifluoroethanol (up to 91% ee).

Rh(I)-catalyzed coupling cyclization of N-aryl trifluoroacetimidoyl chlorides with alkynes: one-pot synthesis of fluorinated quinolines.

[reaction: see text]. Rh(I) complexes were found to catalyze the coupling cyclization of N-aryl trifluoroacetimidoyl chlorides with alkynes to afford 2-trifluoromethylated quinolines in good yields. Various alkynes were applied to this cyclization coupling with regioselectivity.

Diastereoselectivity controlled by electrostatic repulsion between the negative charge on a trifluoromethyl group and that on aromatic rings.

Intramolecular electrostatic repulsions between the local negative charge on a trifluoromethyl group and that on the ortho position of an aryl moiety of a nucleophile was found to be a controlling factor of the diastereoselectivity in a cyclopropanation reaction, in which the electrostatic repulsion was evaluated quantitatively.

Syntheses of optically active trifluoronorcoronamic acids.

Syntheses of optically active trifluoronorcoronamic acid 6 and its diastereomer 9 are described. Highly stereospecific and diastereoselective S(N)2 cyclization of gamma-cyanohydrins 3a and 3b gave cyclopropyl nitriles 4a and 4b. Hydrolysis of the cyano group and deprotection of the amino group of 4a provide trifluoronorcoronamic acid 6. Hofmann rearrangement of the amide which was generated by hydrolysis of the cyano group and oxidative cleavage of the aryl ring of 4b to provide trifluoro-allo-norcoronamic acid 9.

Palladium-catalyzed tert-butoxycarbonylation of trifluoroacetimidoyl iodides.

A modification and details of the palladium-catalyzed tert-butoxycarbonylation of 2,2,2-trifluoroacetimidoyl iodides 1, which gave the iminocarboxylates 2, one of the promising precursors to fluorinated alpha-amino acids, are described. The Pd-catalyzed carbonylation reaction was remarkably promoted by the use of DMF or DMI as an additive, enough to achieve the selective formation of tert-butyl iminoesters. Nucleophilic alkylation of the imine moiety of 2 and subsequent removal of N- and O-protecting groups gave a variety of 2-substituted 2-amino-3,3,3-trifluoropropanoic acid derivatives 3 in high yields.

Lipase-catalyzed transesterification of 2-hydroxy-2-(pentafluorophenyl)acetonitrile leading to (1R,2R)- and (1S,2S)-bis(pentafluorophenyl)ethane-1,2-diol

Optically pure (1R,2R)- and (1S,2S)-1,2-bis(pentafluorophenyl)ethane-1,2-diol (1) were synthesized from key intermediates (R)- and (S)-2-hydroxy-2-(pentafluorophenyl)acetonitrile (2), both of which were prepared by the lipase LIP-catalyzed transesterification (E = 465). The absolute configuration of (S)-2 was determined by X-ray structural analysis after transformation into (S)-alpha-cyano-2,3,4,5,6-pentafluorobenzyl (S)-6-methoxy-alpha-methyl-2-naphthaleneacetate (S,S)-9. In addition, the crystal structure of (S,S)-9 has an interesting well-ordered packing pattern which shows face-to-face stacking interactions and end-to-end parallel contacts between the pentafluorophenyl and 6-methoxynaphthyl groups of the adjacent molecules.

Synthesis of bis- and oligo-gem-difluorocyclopropanes using the olefin metathesis reaction

Synthesis of six types of novel bis- and oligo-gem-difluorocyclopropanes has been accomplished through the olefin metathesis reaction protocol. Two types of ruthenium-based olefin metathesis catalysts were tested: the ruthenium catalyst coordinated with 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene and tricyclohexylphosphine ligands gave better results than the ruthenium catalyst that coordinated with two tricyclohexylphosphine ligands.