Stereoselective oxidative coupling of carboxylic acid derivatives and reductive coupling of cinnamic acid derivatives using chiral auxiliaries are described as the following items. 1) Oxidative homocoupling of chiral 3- (arylacetyl)-2-oxazolidinones with DABCO-TiCl4 or DMAP-TiCl4. 2) Oxidative homocoupling of (4S)-3-(3-arylpropanoyl)-4-isopropyl-2-oxazolidinones and (4R, 5S)-1-(3-arylpropanoyl)-3, 4-dimethyl-5-phenyl-2-imidazolidinones with LDA as a base and TiCl4, PhI (OAc)2, or CuCl2 as an oxidant. 3) Oxidative coupling of (4R, 5S)-1-aroylacetyl-3, 4-dimethyl-5-phenyl-2-imidazolidinones with NaH-Br2 and oxidative intramolecular coupling of diaroylacetate derivatives prepared from (1R, 1'R)-exo, exo'-3, 3'-biisoborneol with NaH-Br2. 4) Electroreductive hydrocoupling of chiral 3-cinnamoyl-2-oxazolidinones and cinnamates of [(1R)-exo]-3-exo-(diphenylmethyl) borneol. 5) Electroreductive cross-coupling of chiral 3-cinnamoyl-2-oxazolidinones with acid anhydrides.
Lewis acid-mediated reactions of acylzirconocene chlorides with aldehydes afforded α-ketols through the nucleophilic addition of an acyl anion. In reactions of acylzirconocene chlorides with α, β-enones, complete regioselectivity (1, 2- or 1, 4-addition) was attained by choosing a suitable catalytic system, that is, Pd (OAc)2-BF3- OEt2 for the 1, 4-addition, and Pd (OAc) 2-2 PPh3 or PdCl2 (PPh3) 2 for the 1, 2-addition. In the 1, 2-selective reaction, the moderately enantioselective 1, 2-addition of acyl anion to α, β-enones was achieved by the use of Pd (OAc)2-2 MOP catalyst. The Pd-catalyzed chemistry of the acylzirconocene chlorides also enabled us to bring about the formations of bicyclo [3.3.0] compounds through the reactions with ω-unsaturated α, β-enones. a-Amino ketones were formed by Yb (OTf)3- or, more interestingly, Bronsted acid-catalyzed reactions with imines. More efficient formations of the α-amino ketones have been carried out through three-component synthesis.
Radical cyclizations are now widely used in organic synthesis for the construction of carbo- and heterocyclic compounds, including natural products. In this review, results of our recent studies on the control of regiochemistry of radical cyclizations are summarized. One factor determining the course (regiochemistry) of radical cyclizations is the reaction temperature used. For example, at a low temperature, i.e., under kinetically controlled conditions, 4-exo-trig cyclization predominated over another possible cyclization, 5-endo-trig cyclization, whereas at a high temperature, i.e., under thermodynamically controlled conditions, 5-endo cyclization products were obtained. Another factor determining the course of radical cyclizations involves the nature of the prefered conformation of the radical precursors. In general, a 5-exo-trig cyclization is prefered over a 6-endo-trig ring closure in systems having an alkenic bond at the 5-position relative to the aryl radical center. We found, however, that N- (ο-bromobenzyl) enamides underwent cyclization in a 6-endo-trig manner to give exclusively a tetrahydroisoquinoline derivative. The mode of the cyclization can be changed to 5-exo by introducing a (Z) -phenylthio group into the terminus of the N-vinylic bond, indicating that the stabilizing effect of the sulfur atom on an adjacent radical center is highly effective for controlling regiochemistry. The introduction of a phenylthio group into the terminus of the N-vinylic bond is also effective for achieving 6-exo-trig cyclization of aryl radicals. Applications of these radical cyclizations to the synthesis of some therapeutically important materials are also presented.
We have focused on the synthesis of azine-type heterocyclic compounds and their conversion into useful functional molecules. In this article, the following points were reviewed. 1) 6-Amino-2, 3-dimorpholinoquinoxalines bearing the amino acid residues at C-6 position were found to be highly-sensitive fluorescent chiral derivatization reagents. 2) A new tripodal heterocyclic hexadentate ligand, in which three sets of 3-hydroxy-4 (1H) -pyridinone and ethyleneoxy chain are linked to tris (carboxyethoxymethyl) ethane was synthesized. The allosteric binding of alkali metal ions to a pseudocryptand formed by the ligand and Ga (III) was discussed. 3) Hydroxyazine-type linear and cyclic hexapeptides were newly synthesized. The iron (M) complex-forming tendency, the absolute configuration, the stability constant, the iron (III) removal from human transferrin, and the growth-promotion activity were discussed. 4) Oxovanadium complexes of 3-hydroxy-4 (1H) -pyridinones were synthesized. The spectroscopic characterization of the complexes was carried out on the basis of 1H-, 51V-NMR, IR, UV-VIS, FAB MS, ESI MS and ESR spectra, and cyclic voltammetry (CV). Further, an extremely high insulin-mimetic activity of bis (1, 4-dihydro-2-methyl-1-phenyl-4-thioxo-3-pyridinolato) zinc (II) complex was also discussed.
Recent progress of the synthetic study by using Masked Acyl Cyanides (MAC reagents) is described. Various kinds of electrophiles like organohalides, aldehydes, ketons, α, β-unsaturated carbonyl compounds, 1, 3-diene monoxides, allylic carbonates and so on can be transformed to amides or esters with one-carbon homologation. Several syntheses of optically active compounds were demonstrated. Racemization of the α-position of the resulting amides and esters was effectively inhibited by the nature of MAC reagents since the resulting carbonyl group is masked as an oxymalononitrile form during the transformation steps. Highly effective one-portion reaction for the connection of three components (aldehydes or ketones, MAC reagent having silyl group, amines or alcohols) was newly developed. A new short-step preparation of MAC reagents is also introduced.
The author describes herein several coupling reactions of terminal alkynes with organic halides, which protocols are recently developed in the author's group. Use of new activators such as silver (I) oxide, tetrabutylammonium fluoride (TBAF), several quaternary ammonium hydroxides, and aqueous ammonia constitute a practical synthetic strategy for the introduction of carbon-carbon triple bond moieties into organic molecules.