We have developed the “cation pool” method in which carbocations such as alkoxycarbenium ions and N-acyliminium ions are generated and accumulated in conventional reaction media by low temperature electrochemical oxidation. The carbocations thus produced are allowed to react with a variety of nucleophiles. Various organic transformations using the cation pool method, such as reductive radical couplings, cationic carbohydroxylations, three-component couplings, and additions of organic radicals, have also been developed. Combinatorial sequential synthesis using the “cation flow” method, in which carbocations are generated in an electrochemical microflow system, has been achieved as well.
Heliannuol sesquiterpenoids have been isolated by Macias from the extracts of cultivated sunflowers (Helianthus annuus L. SH-222) and are believed to be involved in the allelopathic action of sunflowers. The characteristic phytotoxic activity, coupled with their unique structural features, has made these terpenoids desirable targets for synthetic chemists. In this article, the total synthetic studies on heliannuol sesquiterpenoids have been reviewed mainly focusing on our experimental endeavor. In the first part, the first enantioselective total syntheses of (-) -heliannuol D and (+) -heliannuol A have been mentioned. Alternative synthesis of (+) -heliannuol D, the natural enantiomer, has also been described. In the next chapter, syntheses of optically active heliannuols A, K, G, H and L were shown. Interestingly, the structures of heliannuols G and H were revised by our total synthesis. In the last chapter, the syntheses of heliannuols E and C and determination of their absolute structures were described.
Chiral 2-phenylpropanoic acid derivatives and 2-methylchroman-2-carboxylic acid derivatives were prepared as new chiral dopants for nematic liquid crystals. The optically active (S) -2- (4-butylphenyl) propanoic acid was prepared from (S) -2-propanoic acid chloride and butylbenzene using an analogous method employed for the synthesis of ibuprofen. Their helical twisting power (HTP) was determined and the relationship with their functional groups and flexible terminal structures was studied. (S) -1- [4- (trans-4-Butylcyclohexyl) phenyl] -2-phenylpropane-1-one showed a large HTP value 20.4 μm-1 (MHTP = 5.50 μ-1mol-1kg). The HTP was also studied for 2-methylchroman-2-carboxylic acid derivatives having a chiral center in the cyclic structure. The starting material, 6-benzyloxy-2-methylchroman-2-carboxylic acid, was prepared and resolved by a diastereomeric salt formation method. Its ethyl ester showed a good HTP value 11.2 μm-1 (MHTP = 3.65 μm-1 mol-1 kg) showing the rigid cyclic structure having a benzyl group at the 6-position was also effective for chiral induction.
Various water-soluble azacyclophanes have been prepared and exhibited the following unique functions with regard to supramolecular functions in water : (1) The water-soluble supramolecular azacyclophanes composed of an adamantly-appended macrocyclic cyclophane with maltosyl-α-CD demonstrated the potentiality as hosts as well as transporters. (2) The water-soluble bis (cyclophane), tris (cyclophane), and pentakis (cyclophane) were synthesized on the basis of a molecular design that allows the connection of two, three, and five azacyclophanes, respectively. The guest-binding affinity of the present multi (cyclophane) s toward hydrophobic dyes was much enhanced, reflecting multivalency effects in macrocycles. (3) A new convenient strategy for the active sitedirected chemical modification of a lectin surface was demonstrated by using the water-soluble saccharide cyclophane. (4) In addition, a cyclophane-based resorcinarene tetramer, which is constructed with a tetraaza [22.214.171.124] paracyclophane and four resorcinarenes bearing hepta (carboxylic acid) residues that connect the macrocycle through amide linkages, was prepared. The cyclophane-based tetra (resorcinarene) acted as a host for both hydrophobic molecular guests and histone through hydrophobic and electrostatic interactions, respectively.
1-Chlorovinyl p-tolyl sulfoxides, including optically active form, were easily synthesized from carbonyl compounds and chloromethyl p-tolyl sulfoxide in high overall yields. Treatment of the 1-chlorovinyl p-tolyl sulfoxides with cyanomethyllithium gave cyclopentadienyl enaminonitriles in high yields with three consecutive C-C bond-formation. By this method 4, 4-disubstituted 2-cyclopentenones, including optically active form, were synthesized. Asymmetric synthesis of (+) -α-cuparenone was realized by using this method. When cyclic ketones were used in this method, spiro [4.n] alkenones were synthesized in high overall yields. Starting from cyclobutanones, a new synthesis of bicyclo [3.3.0] oct-1-en-3-ones was realized. A new route to fully substituted cyanoallenes was also developed. Reaction of the vinylsulfoxides with N-lithio arylamines was found to give aminoaldehydes, from which α-quaternary α-amino acid derivatives were synthesized. Conjugate addition of lithium ester enolates and lithium amide enolates gave the adducts in high yields with very high 1, 2-, 1, 3- and 1, 4-asymmetric induction from the sulfur chiral center. A new synthesis of optically active carboxylic acids and γ-lactones having a tertiary or a quaternary carbon stereogenic center was realized. A novel method for asymmetric synthesis of both enantiomers of α-substituted carboxylic acid derivatives was also developed by this synthetic method.
The imidazo [1, 2-a] pyrazin-3 (7H) -one (imidazopyrazinone) ring is a core structure of the luminescent substrates isolated from marine bioluminescent organisms, such as the crustacean Vargula (Cypridina) and the jellyfish Aequorea. To develop the bioluminescence chemistry, we revealed the unique π-electronic character of the imidazopyrazinone ring system on the basis of the pioneering study by Goto et al. In this article, we provide an overview of the fundamental chemistry of imidazopyrazinone including the molecular structure, aromaticity of the π-system, molecular orbital, solvatochromism, acid-base behavior, tautomerism, and electron-donating ability. Especially, the imidazopyrazinone π-system having a twitterionic character is sensitively affected by a microenvironment around molecules, to show a continuous absorption-spectral change. Therefore, imidazopyrazinones are useful as functional dyes to indicate a magnitude of an interaction with a microenvironment, such as a hydrogen bond and a Lewis acid-base interaction. We also describe applications of imidazopyrazinone derivatives as indicators for naked eye detection of the hydrogen-bond donor strength of a solvent molecule, the Lewis acidity of a metal ion, and a hydrophobic interaction with a protein.
Vast number of valuable metal catalyzed reactions has been developed to date. One of the important roles of the metals is the activation of an electrophile as a Lewis acid. On the other hand, due to environmental and economical demands, metal-free reactions have been attracting much attention. In this review, reactions catalyzed by urea, thiourea and guanidine are introduced. These catalysts have more than two active hydrogens, which can activate an electrophile through double hydrogen bonding. High enantioselectivity is achieved by tuning of their side chains.
Asymmetric reactions catalyzed by chiral Brønsted acids are reviewed. In recent years, there has been much effort toward the development of an efficient asymmetric methodology using organocatalysts, and some successful examples of such transformations using chiral Brønsted acid catalysts have been reported to date. Among them, this review describes the asymmetric synthesis of nitrogen-containing compounds using chiral Brønsted acid catalysts, which take advantage of the high affinity for weakly basic substrates such as imines.