Cyclopropane amino acids are the amino acid derivatives which contain the cyclopropane ring in their side chain. Various cyclopropane amino acids were isolated from many different natural sources. Along with many efforts to synthesize these natural compounds, studies on the structure-activity relationships of bioactive peptides have highlighted the usefulness of cyclopropane amino acids. Incorporation of cyclopropane amino acids has been achieved for some neuropeptides, hormones, and enzyme inhibitors and these sterically rigid cyclopropane amino acids were found to be a key constituent not only as conformational constraint but also as a structural element to avoid enzymatic degradations. Several distinct success stories have prompted organic chemists to challenge the asymmetric synthesis of optically active cyclopropane amino acids in these years.
Since heterogeneous Ziegler-Natta catalysts usually contain multiple active species with different chemical properties, it is difficult to control the composition and monomer sequence distribution of copolymers by using them as catalyst. In the present paper, therefore, we have prepared both heterogeneous and homogeneous model catalysts which completely differ in stereospecificity and regiospecificity and applied them for olefin copolymerizations to investigate the effect of catalyst stereo- and regiospecificity on copolymers. A detailed analysis of copolymers produced with isospecific and aspecific heterogeneous catalysts has led to the conclusion that isospecific sites give blocky copolymers with less contents of higher olefins while aspecific ones give random copolymers abundant in higher olefin contents. Homogeneous Kaminsky-Sinn type catalysts are known to produce random copolymers. It was found, however, the microstructure of copolymers is slightly dependent upon the stereospecificity, i.e., bulkiness or symmetry of ligand attached to the active site. On the other hand, the Al2O3 supported CpTiCl3 catalyst was found to give atactic polypropene with frequent chemical inversion as well as random olefin copolymers, which are very different from those obtained with ordinary Ti-based heterogeneous catalysts.
VO (OR) Cl2 is revealed to be a Lewis acid with one-electron oxidation capability. The regioselective ringopening oxygenation of cyclic ketones is catalyzed by VO (OEt) Cl2 in ethanol under oxygen to give the diesters or keto esters. The presence of α, β carbon-carbon double bond in the ketones alters the reaction course. 2-Cyclohexen-l-ones undergo dehydrogenative aromatization to give aryl ethers. An oxovanadium compound obtained from VO (OEt) Cl2 and AgOTf or Me3SiOTf works more efficiently. In the cases of 2-cyclopenten-1- ones, 1-acetyl-1-cyclohexene, and β-ionone, allylic oxidation is achieved to introduce an oxo or alkoxyl group at the γ-position. 2-Phenylglycine derivatives are transformed to ethyl benzoate and ethyl phenylglyoxylate by the VO (OEt) Cl2-induced' oxidative deamination and/or decarboxylation. The ring-opening addition of cyclobutanone to olefins bearing an electron-withdrawing group leads to the corresponding E-chloro ester via oxidation of a cyclobutoxide intermediate. Treatment of a mixture of diketene and styrenes with VO (OR) Cl2 gives 3-alkoxycarbony1-2-methyl-5-phenyl-4, 5-dihydrofurans. Oxidative desilylation is selectively realized by one-electron oxidation of organosilicon compounds with VO (OEt) Cl2. Silyl enol ethers undergo the oxidative cross coupling to afford unsymmetrical 1, 4-diketones. Allylic silanes also regioselectively dimerize to 1, 5-hexadienes. Oxidative desilylation of silyl enol ethers and allylic silanes selectively gives γ, δ-unsaturated ketones depending on their redox potentials. The highly stereoselective monodebromination of gem-dibromocyclopropanes is induced or catalyzed by a low valent vanadium species generated from vanadium (III) chloride or CpV (CO) 4 and zinc in dimethoxyethane in a combination with diethyl phosphonate or triethyl phosphite.
The first stereoselective total syntheses of the montanine-type Amaryllidaceae alkaloids, (±) -montanine 1, (±) -coccinine 2, (±) -pancracine 4, (±) -O- acetylinontanine 5, and (±) -brunsvigine 6 are described. The key steps in the reaction sequences are as follows : (1) stereoselective hydroboration-oxidation of exomethylene by means of an intramolecular charge transfer complex to provide alcohol 44 as a single isomer, (2) cyclization of tosylamide alcohol 49 with vitride® [sodium bis (2-methoxyethoxy) aluminum hydride] to provide functionalized 5, 11-methanomorphanthridine 50, which possesses the basic skeleton of montanine-type alkaloids; and (3) conversion of 56 to allylic chloride 57 a by treatment with PhSeCl in MeOH under ultrasonication followed by NaIO4 oxidation. A formal total synthesis of (±) -manthine 3 was also achieved.
Zirconium-mediated carbon-carbon bond forming reactions have been extensively developed for the last decade. An allylic zirconium species and related organozirconium species can be prepared from the reaction of allylic ethers with zirconocene equivalent “Cp2Zr” through β-alkoxide elimination under mild conditions. This methodology is applicable to the ring contraction reaction of vinyl sugar and vinyl morpholine derivatives to give enantiomerically pure polyfunctionalized carbocycles and pyrrolidines with high diastereoselectivity, respectively. The origin of high diastereoselectivity in these transformations was deduced by isolating the nine-membered cyclic intermediate possessing (Z) -allylic zirconium species. Useful applications of this zirconium-mediated ring contraction reaction to syntheses of bioactive compounds are also described. It is also discussed that the diastereoselectivity of the zirconium-mediated coupling reaction of a chiral imine with unsaturated compounds is highly dependent on the generating temperature of zirconacycles.