Palladium-catalyzed cyanation of bromoporphyrins is now realized using cyanoethylzinc bromide as a specific cyanating agent. Although details of the present catalytic process are not clear as yet, we tentatively assume the mechanism as follows. The reaction is initiated by the oxidative addition of Pd(0) to the C-Br bond of the substrate. Subsequent metal ion insertion from the zinc reagent to the porphyrin core synchronously generates the cyanide ion along with evolution of ethylene. Finally, reductive elimination of the resulting Pd(II) cyanide intermediate gives the product. This new protocol provides an easy access to various cyanated Zn(II) porphyrins, including meso-mono-, meso-di-, and β-mono-cyano-substituted Zn(II) complexes.

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The benzynes have served as highly reactive dienophiles in the Diels–Alder reactions to give polyaromatic compounds in a single step, and they have been widely applied to the construction of carbon skeletons of biologically important compounds. However, the regioselective reactions of substituted benzynes have been attained in limited cases.
We present here a novel regioselective preparation of polysubstituted naphthalenes via the Diels–Alder reactions of the 3-silylbenzynes 1. Thus, the reactions of 1 and 4-alkoxy-2-(silyloxy)furans 2 provided naphthalenes 3 with exclusive regioselectivity. Similarly, the reactions of 1 and 2-alkylfurans 4 gave the cycloadducts, but with the opposite regioselectivity. The silyl groups of the cycloadducts 3 were converted into carbon- and oxygen-substituents as well as hydrogen to provide the polysubstituted naphthalenes, which have been hardly available by the existing methods.

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In the course of examination for dehydration of 14-hydroxy-morphinan derivative, we found a novel rearrangement reaction of morphinan skeleton.
When 14-hydroxy-morphinan was dehydrated with thionyl chloride in pyridine, an abnormal rearrangement product was obtained in 28% yield concomitant with an expected dehydration product in 71%. We examined to improve the yield of the abnormal rearrangement. The dehydration was effected in the condition of mesyl chloride and sodium hydride in THF to afford the abnormal rearrangement product in 93%.
We will also detail the reaction mechanism.

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Treatment of t-butyl carbonyl carbamates of α amino acids with KHMDS in DMF at -60^oC gave α-t-butoxy carbonyl α amino acid derivatives in up to 98% ee. This transformation proceeds via migration of a t-butoxy carbonyl group of the chiral enolate intermediates.

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The opioid receptor is classified into three types (mu, delta and kappa). Moreover, the existence of the subtype (mu1, 2, delta1, 2, kappa 1, 2, 3 ) is advocated to each receptor, and the synthesis of selective ligand to each receptor is an important problem. Naltrexone shows strong antagonist activity for the mu-receptor. On the other hand, 14- deoxynaltorexone would be a useful intermediate not only for design of mu-agonist but also for design of selective ligands for each receptor subtype.
Now we established a novel synthetic method of 14-deoxynaltrexone. Naltrexone methyl ether was protected with acetal, and subsequently, dehydrated the 14-hydroxy group with SOCl₂ to give 8,14-dehydro-compound. The product was reduced with PtO₂ under hydrogen to afford the 14-deoxy derivative. The total yield from naltrexone to 14-deoxy compound was 86%. This method provides a useful reaction route to give various important intermediates as a message part.

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We have developed novel ionic chiral ligand, 1-[4-[4-[[[(1S,2S)-2-amino-1,2-diphenylethyl]amino]solfonyl]phenoxy]butyl]-3-methyl-1H-imidazolium mono(trifluoroacetate) salt with trifluoroacetic acid, designed from tosylated chiral diphenylethylenediamine-arene-Ru complex for recycling asymmetric transfer hydrogenation (RCATH) of ketones. The ligand could be applied to RCATH of several acetophenone derivatives to give optically active secondary alcohols in good yield and high enantio selectivity. The RCATH reaction system could be recycled with no significantly loss of activity within five cycles. The RCATH was also applied to asymmetric synthesis of terbutaline, which is one of a clinical therapeutic drug of asthma used as a racemate.

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We have found that the metal salt of trimethylsilyldiazomethane (TMSCHN₂), a quite useful reagent for generating alkylidenecarbenes from carbonyl compounds, can be efficiently used for the preparation of arylpropiolates from arylaldehydes or arylglyoxylates.
Thus, in one-pot process, reaction of the lithium salt of TMSCHN₂ (TMSC(Li)N₂) with arylaldehydes 1 gave arylacetylenes 2 which were treated with n-BuLi, then ethyl chloroformate to give arylpropiolates 3 in good yields. On the other hand, the magnesium bromide salt of TMSCHN₂ (TMSC(MgBr)N₂) reacted chemoselectivety with the ketone moiety of arylglyoxylates 4 affording arylpropiolates 3 via alkylidenecarbene inetrmediates in moderated to good yields.

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The effective use of VIS is a most important research topic at this time of hoped-for development of new energy conversion and energy-using technology; however, there have been no reports about application of photo-oxidation with VIS by a general-purpose fluorescent lamp to fine chemistry. In the course of our study on photo-oxidation, we found that a combination of CBr₄-Ph₃P, a non-metal method, enables us to carry out aerobic photo-oxidation of alcohols to the corresponding carboxylic acids under irradiation of VIS from a general-purpose fluorescent lamp. Aliphatic primary- and secondary alcohols, benzyl alcohols generally afforded the carboxylic acids directly in good to high yield. Our new oxidation method is interesting due to non-use of metals and halogenated solvents, waste reduction, and use of molecular oxygen.

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D-Galactose-containing glycoconjugates play an important role in recognition of cell and immunity. Influenza virus recognizes sialyl(2-3)galactose or sialyl(2-6)galactose residues, such as hemagglutinin on the viral envelope. However, the synthesis of sialyl galactose derivatives needs many protection and deprotection steps, therefore the regioselective deprotection of D-galactose derivatives is required. Molecular Imprinting Polymer (MIP) attracts attention as molecular recognizing artifical polymer corresponding to antibodies and enzymes. Initially, we synthesized templates for the preparation of MIP in order to regioselectively hydrolyze the acetyl groups of 3- or 6- position of D-galactose derivatives, respectively. And then, we synthesized MIP by polymerization reaction. We report the regioselective hydrolysis of the acetyl groups of D-galactose derivatives catalyzed by MIP by monitoring with HPLC.

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Recently we reported that Reformatsky type reactions of ethyl bromodifluoroacetate (1a) and imines with Et₂Zn in the presence of RhCl(PPh₃)₃ gave racemic α,α-difluoro-β-lactams in good to excellent yields. The success shifted us to the next step to get chiral version of them for biological study of an α,α-difluoro-β-amino acid. First we tried reaction of 1a with chiral imine (2a). The reaction gave difluoro-β-lactam (3a) as only one diastereomer. Next plan, we tried the reaction of (-)-menthyl bromodifluoroacetate (1b) with N-benzylidene-4-metnoxybenzylamine (2b) to obtain difluoro-β-lactam (3b) with highly diastereoselectivity. Advantage of this reaction is domino reaction, which perform the diastereoselective addition, followed by self removal of chiral auxiliary.

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Akabori reported that the reaction of N-methylalanine with benzaldehyde at 130 ^oC for 1 h in pyridine gave ephedrine in 16% yield (Nipponkagakukaishi;, 1942;, 64, 608-611). By the detail reinvestigation of this reaction, we found that unstable 3,4-dimethyl-2,5-diphenyl-oxazolidine was formed as an intermediate and this intermediate was easily hydrolyzed by aqueous AcOH to give a mixture of ephedrine and its isomer in 48% yield in one-step. This reaction is very interesting, because it was a new type of reaction involving unprotected amino acids; an alkylation at asymmetric carbon occurred simultaneously with decarboxylation, which was caused via the formation of imminium salt. The presence of electron donating substituent on benzaldehyde increased the yield. For example, p-methoxybenzaldehyde and 3,4-methylenedioxybenzaldehayde gave the products in 72% and 87% yield, respectively.

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We have previously reported phase-transfer catalyzed one-pot synthesis of a-diazo-b-hydroxyesters. This sequential method enables to employ a single phase-transfer catalyst through overall 3 step-reaction without isolation of any explosive intermediates. Further application to establish the synthetic utility of these products as a versatile precursor for various nitrogen heterocycles was studied. Because diazo-functionality was easily converted to the corresponding hydrazones and hydrazines in stereoselective fashion, we focused the efficient preparation of cinnolines and aminoindoline via Cu-catalyzed intramolecular N-arylamination. The cyclization using ortho-iodo substrates in the presence of CuI (10 mol%) with diamine (10 mol%) under quite mild conditions gave the corresponding products of cinnoline, dihydrocinnoline and aminoindoline in high yield. The substrate generality is currently under investigation.

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Alkyl amines represent an important class of chemical transformations that have found extensive use in the construction of vast range of natural products, bioactive molecules, and industrial materials. Such broad utilities have made them important synthetic targets. A main traditional synthetic rout of alkyl amines is direct base-promoted N-alkylation although it includes a lot of problems, such as the use of toxic and corrosive alkylating reagents, the generation of a large quantity of wasteful salts as by-products, and over alkylation. These problems are undesirable in view of environmental concerns. To overcome these difficulties, we have developed Rh/C-catalyzed reductive and catalytic monoalkylation of primary amines using nitriles as alkylating reagents. During the course of further study, we have found the excellent catalytic activity of 10% Pd/C toward the quantitative formation of tertiary amines by the addition of AcONH₄.

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Diastereoselective synthesis of α-amino-H-phosphinates was achieved, which were versatile synthetic intermediates for biologically active alpha-aminophosphinic acid derivatives. The synthetic methodology involves alkylation of racemic aminomethylenephosphinates bearing 1,1-diethoxyethyl group on phosphorus atom and subsequent conversion of 1,1-diethoxyethylphosphinyl moiety to P-H group. The feature of this method is a high diastereoselectivity controlled by the asymmetric center at the phosphorus atom in the alkylation step. The acetal moiety on phosphorus atom of the alkylated products was readily removed under mild conditions giving α-amino-H-phosphinates. This methodology was applicable to preparation of chiral α-amino-H-phosphinates through optical resolution of aminomethylenephosphinates.

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Most of the reported methods for synthesizing O,O-mixed acetals use acid catalyst in the presence of the introduced alcohol. Then, over-reaction affording O,O-symmetrical acetals often occurs, and the yields of the desired O,O-mixed acetals are moderate. We present here a new efficient method for the synthesis of O,O-mixed acetals via the collidinium salts, which are obtained by TESOTf-2,4,6-collidine treatment of acetals, using alcohols as O-nucleophiles. Our method does not cause over-reaction. The yields of O,O-mixed acetals are very high. Characteristic feature of our method is that the reaction conditions are weakly basic. Then, many acid-sensitive functional groups, which cannot be used in the previously reported methods, are tolerated in our method. Furthermore, the method was also applied to the synthesis of O,S- and N,O- acetals.

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The cabonylative cyclization of 1,1-diethynyl acetates mediated by Ph-box/Pd(TFA)2 afforded functionalized 4-cyclopentene-1,3-diones as a major product. On the other hands, without using box ligand produced methoxycarbonylated orthoesters as a major product. Treatment of 1,1-diethynyl acetates in the presence of Au or Pt catalyst(5 mol %)in methanol for 20-48 hours gave ketoesters and lactones in 46-53% and 27-47% yields, respectively. In these reactions, an oxygen atom is introduced to the first acetylene moiety in accordance with Markovnikov's rule, and to the second acetylene moiety with anti-Markovnikov regioselectivity.

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Recent investigations on palladium chemistry has revealed that functionalization of aromatic C-H bond of aromatic group is highly effective for the construction of fused aromatic rings. We investigated the tandem cyclization of dibromide 1 under various reaction conditions. After considerable experimentation, we found that the dibromide 1 yielded the desired tetracyclic product 3 in the presence of a catalytic amount of palladium acetate, PCy3-HBF4 and Cs2CO3 in 1,4-dioxane. It is noteworthy that dibromide having a heteroaromatic ring can also be used for the tandem cyclization involving the sequencial functionalization of the aromatic C-H bond. This tandem cyclization in which two carbon-carbon bonds are formed is synthetically useful since complex heterocyclic skeletons can be constructed directly form readily prepared dibromides.

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We recently reported palladium(0)-catalyzed synthesis of medium-sized heterocycles based on our recent discovery that bromoallene can act as allylic dication equivalents in the presence of a palladium catalyst in alcohol. We planned preparation of cyclic sulfamides by intramolecular diamination of bromoallenes.
We investigated the tandem cyclization of the bromoallenes in the presence or absence of palladium(0) and found that the palladium-free reaction of bromoallenes having a sulfamide group with a four-atom tether provided the cyclic sulfamides with a bicyclo[4.3.0]nonane skeleton. This result is in striking contrast to the palladium-catalyzed reaction, which strongly promotes the first cyclization at the central carbon atom of bromoallenes to give cyclic sulfamides having a bicyclo[5.3.0]decane skeleton selectivity. Formation of bicyclic sulfamides with a bicyclo[3.3.0]octane skeleton will be also presented.

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Recently, a large number of N-heterocyclic carbene (NHC) transition metal complexes have been prepared and the catalytic activity of these complexes turned out to be very high. Especially, Pd NHC Complexes expected to be alternatives to phosphine Pd complexes that are widely used for the C-C coupling reactions. We synthesized new Pd NHC complexes derived from 2,7-dimethylnaphthalene and the dimeric structure was confirmed by an X-ray study.
The catalytic activities of the complexes in Mizoroki-Heck reaction were examined and high catalytic activity was observed in many reactions. For example, the reaction of 4-iodoanisole with n-Bu acrylate proceeded at 80 ^oC in the presence of sodium formate (0.1 equiv), i-Pr₂NEt (1.1 equiv), and a small amount of the Pd NHC complex 1 (0.02 mol%) in DMF, and the product was isolated in 88 % yield.

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The enantiospecific coupling reactions of organoboronic acids with propargylic compounds have been achieved using palladium catalyst. The reaction of the optically active propargylic compounds having a various leaving groups with arylboronic acid in the presence of palladium catalyst affords the aryl-substituted allenes in moderate to good yields. The enantiomeric excess of the products were strongly dependent on the kind of leaving group, and they were sometimes lack of reproductivity. After several attempts, we found that the highly enantiospecific process has been proceeded by carrying out the reaction in the presence of phosphate buffer in aqueous solution. Under this reaction condition, various optically active allenes can be easily synthesized from the corresponding propargylic compounds with arylboronic acids.

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The development of modified Pd catalysts for chemoselective hydrogenation has been a major interest in organic chemistry. While many catalyst poisons have been evaluated to obtain chemoselective catalytic systems, only a few studies, such as the Lindlar catalyst and Rosenmund's reaction, have been accepted as applicable methodologies. Recently, we have demonstrated the addition of a catalytic amount of diphenylsulfide as a mild catalyst poison to the reaction system selectively suppressed the activity of Pd/C toward many reducible functionalities such as aromatic ketone, aryl chloride, N-Cbz, and benzyl ester. Furthermore, we developed a heterogeneous Pd/C-diphenylsulfide complex (Pd/C[Ph₂S]) that selectively catalyzed the hydrogenation of multiple bonds, azides, and aromatic nitro functionalities with many other reducible functionalities intact.

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Asymmetric synthesis of hexahydroxydiphenoyl (HHDP) and valoneoyl groups is an important subject because these units are common structures in natural products and some of them exhibit interesting biological properties. We demonstrate a palladiumd-catalyzed aryl-aryl coupling reaction and a lactone-opening reaction to prepare chiral biphenyl compounds. The palladium-catalyzed reaction of phenyl benzoate afforded the corresponding lactone, which was subjected to a diastereoselective lactone-opening reaction using protected sugar alkoxide. After several steps, both enantiomers were obtained in high optical purities. On the other hand, an enantioselective reduction of the lactone compounds using BH₃-oxazaborolidine system was examined to form the axially chiral biphenyls. An application of this method to the synthesis of the valoneic acid derivative will also be discussed.

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PPdCl₂(MeCN) ₂ (10 mol%) catalyzed reactions of cis and trans -non-3-ene-2,8-diols under mild conditions gave (E) 2,6-disubstituted cis-tetrahydropyran and trans-tetrahydropyran respectively in high yields with excellent diastereoselectivities (>20 : 1). A new stereogenic center is generated on the tetrahydropyran ring by 1,3-chirality transfer from the chiral allylic alcohol via a syn S_N2^' type process.
Base on this methodology, the stereoselective construction of the tetra-substituted carbon on the pyran ring was also established from the trisubstituted alkenyl diol and the stereoselective total synthesis of diospongins A and B were completed.

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Since unique physicochemical properties of fluorinated molecules, there has been an increasing upsurge in the development of novel methodologies for the synthesis of fluorinated molecules. In particular, fluoroalkene units are important class of molecules such as liquid-crystalline materials as well as peptide isosteres and enzymatic inhibitors. In this study, we developed a novel synthetic methodology for fluoroalkene compounds based on the concept of palladium-mediated carbon-fluorine bond cleavage. A range of allylic difluorides with various functional groups was converted stereoselectively to fluoroalkene compounds by the reaction with two equivalents of phenylsilane in the presence of a catalytic amount of allylpalladium chloride dimer, 1,3-bis(diphenylphosphino)propane and triethylamine.

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Stereoselective construction of five-membered N- or S-heterocycles is of great importance in the field of synthesis of natural or unnatural products having powerful and diverse biological activities.
We will present the gold-catalyzed cycloisomerization of various aminoallenes affording the corresponding 3-pyrrolines in good to high yields with complete axis-to-center chirality transfer, as well as cycloisomerization of thioallenes leading to 2,5-dihydrothiophenes. In each reaction, gold(I) catalysts were more active than gold(III) catalysts. The later reaction is the first example of gold-catalyzed carbon-sulfur bond formation reaction.

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Trehalose has been widely found in nature, and its medical use is recently expected. We investigated the synthesis of several non-reducing disaccharides as trehalose mimics by the Lewis acid-promoted dehydrative glycosylation. The dehydrative glycosylation using 2,3,4,6-tetra-O-benzyl-D-glucopyranose was catalyzed by 20 mol% Bi(OTf)₃ as the activator and the trehalose derivative was successfully obtained in good yield. Moreover, we investigated the synthesis of the trehalose mimics into which the 1-C-methyl-D-hexopyranose derivatives were incorporated.1 The 1-C-methyl-D-hexopyranosylation to several aldopyranoses was efficiently catalyzed in the presence of only 5 mol% Bi(OTf)₃, and several kinds of trehalose mimics of non-reducing disaccharides were obtained in good yields. Our Bi(OTf)₃-catalyzed dehydrative glycosylation was also applicable to the synthesis of glycosides using ordinary alcohols.

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While multi-component reaction (MCR) is a powerful approach to the development of efficient and practical synthetic methods that minimize the reagents, solvents, cost, time, and formation of waste, a catalytic tandem reaction including MCR would be more attractive to achieve this goal. We investigated tandem three-component coupling-indole formation using some ethynylanilines, secondary amines, and paraformaldehyde under various conditions. We found that this tandem reaction requires only 1 mol % of CuBr and 1.1 equivalents of amine components to give the desired 2-(aminomethyl)indoles in high yields. Furthermore, in combination with the palladium-catalyzed C-H activation, this MCR-indole formation is also applicable to the two-step synthesis of polycyclic indoles such as dihydrobenzoazepine-fused indole and tetrahydropyridine-fused indole in high chemical yields.

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A general catalytic allylation of simple ketoimines was developed using 1 mol % of CuF(PPh₃)₃ as catalyst, 1.5 mol % of La(OⁱPr)₃ as the cocatalyst, and stable and nontoxic allylboronic acid pinacol ester as the nucleophile. This reaction constituted a good template for developing the first catalytic enantioselective allylation of ketoimines. In this case, using LiOⁱPr as the cocatalyst produced higher enantioselectivity and reactivity than La(OⁱPr)₃. Thus, using the CuF-cyclopentyl-DuPHOS complex (10 mol %) and LiOⁱPr(30 mol %) in the presence of ^tBuOH (1 equiv) produced high enantioselectivity up to 93% ee from range of aromatic ketoimines. Mechanistic studies indicated that LiOⁱPr accelerates the reaction by increasing the concentration of an active nucleophile, allylcopper.

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In this presentation, we hope to report two types of transition metal-mediated asymmetric reactions using P-chirogenic diaminophosphine oxides (DIAPHOX). First, a general and highly enantioselective synthesis of cyclic aza-Morita-Baylis-Hillman (aza-MBH) reaction products is presented. Cyclic aza-MBH reaction products was obtained in excellent yield with up to 99% ee, and could be converted into various chiral synthetic fragments such as cyclic beta-amino acid derivatives. An Ir-catalyzed asymmetric allylic amination using chiral diaminophosphine oxide is also reported. Asymmetric allylic amination of terminal allylic carbonates proceeded in the presence of 2 mol % of Ir catalyst, 2 mol % of chiral diaminophosphine oxide, 5 mol % of sodium hexafluorophosphate, and BSA, affording the chiral branched allylic amines in up to 95% ee.

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The development of catalysts for Mannich-type reactions that afford anti-products with excellent diastereo- and enantioselectivities is a significant challenge. We have developed pyrrolidine-derived catalysts bearing an acid group at the 3-position of the pyrrolidine for direct enantioselective anti-selective Mannich-type reactions of unmodified aldehydes or ketones with N-p-methoxyphenyl-protected alpha-imino esters. Reactions of aldehydes catalyzed by (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid and reactions of ketones catalyzed by (R)-3-pyrrolidinecarboxylic acid (or (R)-beta-proline) afforded anti-Mannich products in good yields with excellent diastereo- and enantioselectivities. The results indicate that the acid group on pyrrolidine ring of the catalyst has a significant role in directing the stereoselection of the catalyzed reaction.

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Regioselective functionalization of multi-functionalized substrates is one of the goals of current research toward the development of the advanced molecular transformation for the next generation. Here, we report a highly regioselective acylation of sugar derivatives with chiral nucleophilic catalysts. Treatment of a sugar derivative with 1 mol% of a catalyst and 1.1 mol eq. of isobutyric anhydride in chloroform gave the 4-acylated derivative and the 3-acylated surrogate in a 99:1 ratio in 98% yield. The corresponding 6-isomer, 2-isomer, and di-acylated isomers were not detected at all.

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We started the project on the enantioselective total synthesis of the structurally divergent cardenolides via a convergent approach which would be useful for the SAR study. We report herein the new enantioselective total synthesis of (+)-digitoxigenin in a convergent manner using two chiral fragments prepared via the catalytic asymmetric intramolecular cyclopropanation and baker's yeast mediated reduction, respectively. This total synthesis features the catalytic asymmetric IMCP reaction developed by us, which has been widely used to prepare various chiral building blocks for the enantioselective natural product synthesis. The tricyclo[4.4.0.0^5,7]decene derivative (>99% ee, recryst) prepared via the catalytic asymmetric IMCP reaction was successfully applied to the enantioselective synthesis of the fragment of (+)-digitoxigenin. Further efforts to reduce steps of this total synthesis will be discussed in this presentation, too.

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Development of Practical Synthesis of Halichondrins

The halichondrins (especially halichondrin B) have received much attention due to their intriguing structures and extraordinary in vitro and in vivo antitumor activity. Despite several attempts, there is no established way to supply a large quantity of halichondrins from the natural source. Since the first and only total synthesis of halicondrin B in 1992, the continuing effort of our group is to establish a practical organic synthesis to produce a large quantity of halichondrins, particularly the right-half that exhibits the same antitumor activities as the natural product, for cancer chemotherapy. This presentation will report recent progress toward this aim:
1. New Catalytic Cycle for Couplings of Aldehydes with Organochromium Reagents.
2. Catalytic Ni/Cr-Mediated Macrocyclization without Use of High-Dilution Techniques.
3. A Remarkably Effective Device for Forming the C8-C14 Polycyclic Ring System.

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Leustroducsin B, a metabolite of Streptomyces platensis SANK 60191, exhibits induction of a colony-stimulating factor and thrombopoiesis. We synthesized leustroducsin B by taking a highly convergent route, in which the molecule was divided into three segments A, B and C. Julia coupling reaction of the segment A with the segment B provided E-olefin. α,β-Unsaturated lactone ring formation, iodomethylenation and introduction of nitrogen function were successfully achieved. Stille coupling reaction of iodomethylene with the segment C provided Z,Z-diene. Concerning introduction of the phosphate moiety, our method was applied as a key reaction. That is, construction of cyclic phosphate, followed by selective hydrolysis, afforded the phosphate group. Finally, the total synthesis of leustroducsin B was accomplished by the removal of protecting groups successfully.

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Reported here for the first time are the stereoselective synthesis and reaction of simple silver (Z)-enethiolates, which serve as a stabilized (Z)-enethiol storage. In contrast to labile enethiols, silver (Z)-enethiolates are stable even in solutions, and their isolation and purification are very simple. The method for synthesis of silver (Z)-enethiolates involves an unusual vinylic S_N2 reaction of (E)-vinyliodane(III) with thiobenzamides yielding the inverted (Z)-S-vinylthioimidonium salts, followed by their regioselective C-S bond cleavage with silver acetate. Alkylation, arylation, and Michael addition of silver (Z)-enethiolates yielding (Z)-vinyl sulfides was dramatically accelerated by the addition of Bu₄NI (LiI), which probably generates reactive ammonium (Z)-enethiolates with an increased nucleophilicity.

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Recently, we have developed the strong Brønsted acid-catalyzed intramolecular cyclization reaction of methyl 3-aryl-2-nitropropionates to give 4H-1,2-benzoxazines. This reaction can be regarded as an oxygen-functionalization of the aromatic ring wherein the oxygen atom is derived from the nitro group. We investigated the scope and mechanism of the present cyclization. The reaction rate is strongly influenced by the acidity of the reaction medium, which indicated the intermediacy of the O-protonated aci-nitro species. Experimentally, we excluded the 6π electrocyclization mechanism involving deprotonation of the benzyl proton of the protonated aci-nitro species. Experimental observation and theoretical calculations suggested involvement of dicationic intermediate and an asynchronous 1,3-dipolar cyclization between the aromatic ring and the O-protonated aci-nitro moiety.

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Diastereoselective reaction of prochiral cation with enol acetates and 1,3-dicarbonyl compounds was investigated. The secondary benzylic cation generated from 1 reacted with enol acetate 2 to gave (RS, SR)-3 in 97% yield with 97% de. The enol tautomer of the 1, 3-dicarbony compounds also worked as the nucleophile. The reaction of 1 and 5,5-dimethylhexane-2,4-dione proceeded with good diastereoselectivity, and the modification of the α methyl group into the branched chains displayed excellent selectivity (up to 95% de). The diastereoselectivity in the reaction of 1 and methyl pivaloylacetate was changed depending on the catalysts. Rare earth metal, except cerium, triflate-catalyzed reaction gave (RS, RS)-products, and Hf, Ce, and Cu triflate-, Ru and V Lewis acid-catalyzed reaction gave (RS, SR)-products.

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The catalytic hydrogenation of aromatic rings is an important technology for the synthesis of cyclohexane derivatives, which are useful as the intermediates or raw materials of the pharmaceuticals and chemicals, due to its simplicity. However, it is very difficult to hydrogenate the aromatic rings under mild conditions because of the high resonance stabilization energy. During our study to develop new synthetic methodologies using heterogeneous transition-metal catalysts, we have found an environmentally-friendly hydrogenation method for aromatic compounds catalyzed by Rh/C in water at 80 degree under 5 atm of hydrogen pressure. Furthermore, the hydrogenation was achieved under ordinary pressure by using i-PrOH as a solvent. The present mild method could be applied to the hydrogenation of a variety of aromatics including the heteroaromatic compounds.

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