Trifluoromethylated compounds have accepted great attention because of their unique nature for material sciences and biological activities for medicines and agrochemicals. Recent advances in trifluoromethylation which include chemical and electrochemical trifluoromethylations and synthetic blocks for trifluoromethylated compounds are summarized.
Trifluoromethyl carbonyl compounds were found to react as a good enophile due to the high electronegativity of a trifluoromethyl group. Thus, hexafluoroacetone reacts with terminal olefins without a catalyst, while other trifluoromethyl ketones and trifluoroacetaldehyde are less reactive and react only in the presence of Lewis acid. Interestingly, an inner olefin, 2-octene, hardly reacts with hexafluoroacetone, while it reacts with other trifluoromethyl carbonyl compounds in moderate to good yields. This inversion of the order of reactivity is explained by a large steric effect of the trifluoromethyl group, although it is referred as a “mimic” of a methyl group. It seems to be a little larger than a sec-butyl group. The ene reaction products, trifluoromethylated homoallyl alcohols, are useful intermediates for various types of trifluoromethyl compounds. General procedures for their conversion to trifluoromethylated dienes, tetrahydrofurans, and tetrahydropyrans are introduced. Products from trifluoroacetaldehyde were oxidized to trifluoromethyl ketones, Grignard and Wittig reactions of which are also discussed from the view point of reactivity and steric effect of a trifluoromethly group. Further, application of this reaction for the synthesis of fluorine analogues of natural products, p-and m-menthane derivatives, are presented.
Dications bonded by two positively charged heteroatoms have received a little attention, and study of their properties is of great interest. This article presents the preparation, structure, and properties of σ-bonded dications from the medium-sized cyclic compounds containing S, Se and Te atoms. Both the oxidation of 1, 5-dithiacyclooctane (1, 5-DTCO), the related selenium and tellurium derivatives (1, 5-DSeCO, 1, 5-DTeCO), and their dibenzocyclooctane derivatives using either concd H2SO4 or oxidizing agent such as NOBF4 and the treatment of their monooxide in concd H2SO4 or with (CF3SO2) 2O revealed the formation of dications containing transannular bond between two heteroatoms. The structures of the dication salts of 1, 5-DTCO and 1, 5-DSeCO were determined by X-ray crystallographic analysis. These dications act as an oxidant or as an electrophile depending on the added reagents. These new species are of particular interest and become attractive if one could prepare the analogous derivatives bearing multiheteroatoms. As typical example, inspection of the spectrum of the dication of the tris-sulfide, 1, 11- (methanothiomethano) -5 H, 7 H-dibenzo [b, g] [1, 5] dithiocin, and its oxides in concd D2SO4 indicated that the central sulfur atom should have a hypervalent bonding structure composed of two sulfur and two carbon ligands i.e., 10- S-4 (C2S2).
Preparations of optically pure short- to long-chain β-, γ-, and δ-hydroxy acids with R configuration, α-methyl-β-hydroxy acids with anti-2R, 3R configuration, 1, 2-alkanediols with R configuration, and 1-acetoxy-2-alkanols with S configuration are described, by use of asymmetric reduction of the corresponding keto compounds with bakers' yeast. The high optical purity of the products is attributable to the carboxy group in the keto acids and to the substrate specificity of the enzymes involved in the reductions, based on comparison of the keto acids and keto esters as substrates and isolation of the reducing enzymes from bakers' yeast.
Optically active 2-methyl-3-hydroxy propionic acid derivatives which are expected to be useful building blocks for the synthesis of polyoxo-macrolide antibiotics or the related bioactive compounds have been synthesized based on the asymmetric hydrolysis using various industrialized lipases. As an example of synthetic studies using these synthons, a total synthesis of the aglycone of venturicidins A and B is described. Hydrolysis of water-insoluble substrates with lipases immobilized with celite or prepolymer (ENTP-4000) proceeds even in organic solvent. However improvement of efficiency is required. Thus a new immobilization method was developed. Namely, an aggregate of lipases with various phospholipid analogue whose hydrophobic aliphatic chains are linked by ether bonding was found to catalyze an asymmetric hydrolysis much more effectively than the previous immobilization methods.
Related to antiviral agents, nucleoside antibiotic oxetanocin-A isolated from culture broth of Bacillus megaterium NK 84-0218 served potent biological activities against such virus strains as HIV, HCMV and HSV. Of interest is the novel oxetanoside moiety (four-membered ring sugar) of this antibiotic which would promise developments of new antiviral agents. We describe herein total synthesis of oxetanocin-A as well as new oxetanose chemistries. Recent progress of nucleoside analogues relevant to oxetanocin-A is also included.