Several novel reactions are developed utilizing the electron-deficient nature of terminal alkyne-W (CO) 5 π-complexes and/or their isomerized vinylidene complexes. Terminal alkynes having a silyl enol ether moiety in the molecule undergo endo-selective cyclization using a catalytic amount of W (CO) 5 (thf). In some cases, both exo-and endo-selective cyclizations are achieved depending on the reaction conditions. Iodinated vinylidene intermediates are generated from the corresponding iodoalkynes and W (CO) 5 (thf), and are employed for the related cyclizations. Electrocyclization of o-ethynylphenyl ketones gives novel benzopyranylidene complexes, which undergo Diels-Alder reaction with electron-rich alkenes to give substituted naphthalenes. Furthermore, the reaction of o-ethynylphenyl ketones and electron-rich alkenes in the presence of a catalytic amount of W (CO) 5 (thf) proceeds through the novel tungsten-containing carbonyl ylides, which react with the electron-rich alkenes in a [3+2] -cycloaddition manner to give polycyclic compounds.
The previous studies on rhodium chemistry directed us to investigate the substituent effect of silicon on an electrocyclic ring-opening reaction of cyclobutene. It was discovered that a silyl substituent accelerates the reaction and prefers inward rotation, giving the Z-isomer. These intriguing effects were explained by the electron-accepting interactions between the low-lying σ* orbital of the silicon atom and the HOMO orbital of the opening cyclobutene system, possible only in the inward transition state. On the basis of this finding, a novel method for the stereoselective synthesis of functionalized 1, 3-butadiene derivatives from cyclobutenones was developed.
The reducing ability of manganese metal can be utilized effectively by treatment with a catalytic amount of PbCl2 and Me3SiCl. This article discusses the following specific themes using the activated manganese metal as a reductant. 1) Generation of alkyl radicals and their trapping with α, β-unsaturated esters. 2) Three-component coupling reactions of alkyl iodides, electron-deficient olefins, and carbonyl compounds based on the concept of sequential generation of a radical and anionic species. 3) Sequential 1, 4-addition. and Claisen rearrangement. 4) Generation of non-stabilized carbonyl ylides. 5) Selective reduction of iodoform and its application to the synthesis of alkenylsilanes.
Palladium-catalyzed synthetic transformations (π-allylic substitution, carbonylation, cross-coupling, etc.) were achieved in water by use of amphiphilic polystyrene-poly (ethylene glycol) resin (PS-PEG) -supported palladium-phosphine complexes. Asymmetric allylic alkylation of cyclic allyl esters was catalyzed by a palladium complex of a PS-PEG-supported chiral (imidazoindole) phosphine ligand with high enantioselectivity of up to 99% ee.
Novel synthetic strategies for the preparation of fluorinated amino acids are described. Asymmetric synthesis of fluoro amino acid derivatives was accomplished by (i) diastereoselective alkylation of chiral glycine Schiff bases, (ii) diastereoselective intramolecular cyclization of chiral γ-cyanohydrins and (iii) catalytic enantioselective hydrogenation of fluorinated iminoesters.
This article surveys investigations on stereospecific organic photoreactions utilizing well-organized aggregated structures of molecules formed in the interlayer spaces of inorganic layered host compounds. In the beginning sections, the chemical compositions and structural features of the layered hosts and their unique adsorption properties are described, as well as the aggregated structures of the guest molecules. The later sections describe various organic photoreactions, including [2+2] photocycloadditions, photopolymerization and the photopinacolization of aromatic olefins and/or aromatic ketones, while the stereochemistry of the photoreactions is discussed in relation to the aggregated structures of the guest molecules.
Oxime ethers connected by a tether to aldehydes or ketones efficiently cyclized via stannyl radical addition-cyclization to give a new entry to heterocyclic amino alcohols. The SmI2-induced radical cyclization was found to be effective for preparing cyclic trans-amino alcohols. These radical reactions provide a novel method for the synthesis of (-) -balanol, aminocyclitols, 1-deoxynojirimycin, 2-substituted 5-amino-4-piperidinol, and nucleoside analogs. The sulfanyl radical addition-cyclization-elimination reaction was developed, which was successfully applied to the synthesis of (-) -kainic acid. The sulfanyl radical addition-cyclization of oxime ethers gave a method for synthesis of rigidified cyclic β-amino acids. The carbon radical addition-cyclization reaction of substrates having two different radical acceptors such as acrylate and aldoxime ether moieties proceeded even in aqueous media via a diastereoselective tandem C-C bond-forming process, providing a method for asymmetric synthesis of γ-butyrolactones and γ-amino acids.
Selective inhibitors of enzymes are useful tools to unravel the chemical and biological functions of enzymes. In particular, stable compounds that resemble the transition state (transition-state analogs) are extremely useful in understanding the catalysis of enzymes from the structural and mechanistic points of view, because the basic principle underlying enzyme catalysis is to stabilize the transition state selectively. According to this principle, we have designed and synthesized a series of phosphinate- and sulfoximine-based transition-state analog inhibitors of ATP-dependent ligases such as γ-glutamylcysteine synthetase, glutathione synthetase and asparagine synthetase A. We also synthesized a monofluorophosphonate derivative of glutamic acid for mechanism-based affinity labeling of γ-glutamyl transpeptidase. These inhibitors have been used successfully for the X-ray crystallography or mass analysis of the enzymes to identify the key catalytic residues responsible for catalysis, and for understanding the recognition of the substrate in the transition state in energetic terms.
Enantioselective deprotonation reactions of prochiral 4, 4-disubstituted cyclohexanone, 3-substituted cyclobutanones and 3, 5-dioxygenated cyclohexanones with a chiral lithium amide bases in the presence of silylating agents, were carried out to give the corresponding silyl enol ethers. The silyl enol ether obtained from 4-methyl-4-tolylcyclohexanone was converted to (+) -α-cuparenone. On the other hand, the silyl enol ethers derived from 3-substituted cyclobutanones were utilized in the synthesis of naturally occurring (-) -methylenolactocine and several kinds of lignan lactones, and also in the synthesis of medicinally important compound, (R) - (-) -rolipram. Moreover, the silyl enol ethers prepared from prochiral 3, 5-dioxygenated cyclohexanones were employed as the starting materials in the synthesis of biologically important compounds, such as HMG-CoA reductase inhibitor and antiobesity agent, tetrahydrolipstatin, with the opposite mode of asymmetric induction even by using the same chiral amide base. Finally, a synthetic procedure for enantiomerically enriched 5-hydroxycyclohex-2-enone was established by elimination of the alkoxide group in the chiral silyl enol ether, which was further transformed into an inositol phosphatase inhibitor.
In this review article, we report our recent contributions to the total synthesis of the highly symmetric squalene-derived cytotoxic triterpene polyethers, teurilene (3), (+) -14-deacetyl eurylene (1), (+) -eurylene (4), (-) -glabrescol (5), and (-) -longilene peroxide (2), based on the concept of two-directional synthesis utilizing their intrinsic molecular symmetry as the fundamental strategy. In the course of these synthetic studies, syn oxidative cyclizations of bishomoallylic tertiary alcohols promoted by rhenium (VII) oxide have been accomplished with excellent diastereoselectivities. The critical trans or cis selectivity between the 2- and 5-positions of the tetrahydrofuran (THF) ring in the products has been observed, depending on the substrates employed. In addition, the meso structure 6 originally proposed by Jacobs et al. has been revised to the optically pure C2 symmetric structure 5 through its enantioselective total synthesis. Furthermore, the unknown absolute configuration of longilene peroxide has been determined by this synthesis as shown in the structural formula 2.