Carbon-carbon bond cleavage reactions of organic compounds using transition metal complexes are reviewed. The reactions are first classified by the bond order; (i) carbon-carbon single bond cleavage, (ii) carbon-carbon double bond cleavage, and (iii) carbon-carbon triple bond cleavage. For the carbon-carbon single bond cleavage reactions, reactions are classified by the functional groups of the organic compounds. It is shown that in many cases the β, γ-carbon-carbon bond of the organic molecules on metals tends to be cleaved formally. In the case of the carbon-carbon double bond, there are only some examples of the direct cleavage by metals such as a ketene which produces a carbonyl-carbene complex. The direct cleavage of the double bond by metals, which formally affords bis-carbene, is not favorable. In contrast, the carbon-carbon cleavage of the triple bond is achieved by the multi-metal systems which stabilize the cleaved fragments.
Summarized in this article are our total syntheses of Ecteinascidin 743 (Et 743, 1) which is an extremely potent antitumor alkaloid isolated from a marine tunicate, Ecteinascidia turbinata. Based on promising results in phase II and III clinical trials, Et 743 (1) is likely to become the first anticancer drug among marine natural products. The novelty of its structure, the remarkable biological activities, and its natural scarcity have made it an attractive target for total synthesis. In 2002, we accomplished a convergent and stereocontrolled total synthesis of 1 that would potentially lead to the development of a practical synthesis of this important compound. Synthesis of the left segment 77, a highly functionalized (R) -arylglycinol derivative, involves a Mannich-type reaction of phenol 73 with the chiral template 65 developed recently in our laboratories. The right segment 81, (S) -iodophenylalanine derivative, was synthesized by employing DuPHOS-Rh mediated asymmetric hydrogenation as the key step. These two segments were efficiently coupled by the Ugi's 4 CC reaction, and transformed into the cyclic enamide 87 via diketopiperazine 86. Intramolecular Heck reaction of the enamide 87 proceeded smoothly to give 88, containing the bicyclo [3.3.1] skeleton, in high yield. Construction of B-ring was performed by the phenol-aldehyde cyclization of 95, which was invoked by hydrogenolysis of the benzyl groups, giving the desired pentacycle 96 with requisite oxidation state at C-4 position. An acid-induced intramolecular sulfide formation provided the sulfur-containing ten-membered lactone 100. Finally, construction of tetrahydroisoquinoline moiety by the Pictet-Spengler reaction and treatment with AgNO3, was successfully converted to ecteinascidin 743 (1).
A novel method for oligonucleotide synthesis on the basis of chemoselective phosphonylation is described. Nucleoside 3'-H-phosphonate monomers without amino protection were synthesized by the O-selective phosphonylation of nucleosides bearing the free amino and 3'-hydroxy groups. It was found that the amino groups of nucleosides were not modified during internucleotidic bond formation when carbenium and phosphonium compounds were employed as condensing reagents in the present H-phosphonate method. A mechanism for the O-selective condensation was investigated in detail by means of 31P NMR spectroscopy as well as ab initio molecular orbital calculations. The internucleotidic H-phosphonate linkages were oxidized with N-sulfonyloxazilidine derivatives in the presence of silyating reagents under unhydrous conditions without degradation of the oligonucleotide chain. The present method was found to be effective for the synthesis of base-sensitive DNA derivatives bearing various functional groups.
Unsaturated-sugar nucleosides have been shown to serve as versatile substrates for constructing C-C bond at the sugar portion. Various types of appropriate reactions were adopted to 1', 2'-, 2', 3'-, 3', 4'-, and 4', 5'-unsaturated derivatives. These are electrophilic addition followed by substitution with organosilicon and organoaluminum reagents, radical-mediated 1, 2-acyloxy migration of the adducts, nucleophilic addition of benzenethiolate followed by radical substitution, aldol reaction of an enol ester, Pd-catalyzed cross-coupling and halogen-lithium exchange reactions of nucleosidic vinyl bromides, SN2' reaction, addition reaction of carbon radicals, and epoxide ring opening with organometallic reagents. Consequently, C-C bond formation at the 1'-, 2'-, 3'-, 4'-, and 5'-positions of nucleoside became possible.
The 2, 4-pentanediol (PD) -tethered reaction is a stereocontrolled reaction having versatile applicability. When reactant and reagent elements are connected through a PD tether prior to their reaction, stereochemical purity of the product is very high for nine different types of reactions so far studied. Selectivity of one of the reactions shows temperature independency in a wide range from -78 to 150°C, which indicates that the selectivity is governed by the entropy term. The strict stereocontrol at the high reaction temperature can be extended to vapor phase reaction performed above 250 °C. To understand how the two methyl groups on the PD tether stereocontrol the reaction, a new parameter, chiral perturbation factor, is introduced. By this analysis, it is disclosed that the methyl groups do not promote large activation enthalpy change for both diastereomeric processes. In contrast, change in the activation entropy is large and in opposite sing, which should be an origin of the strict stereocontrol by the PD tether.
Allylation of aldehydes by an allyl-transfer reaction from the γ-adducts of homoallylic alcohols has been successfully carried out to give the corresponding α-adducts regioselectively. This unusual allylation reaction appears to proceed stereoselectively through a 2-oxonium [3.3] -sigmatropic rearrangement with six-membered cyclic chair-like transition state. We applied this for asymmetric alk-2-enylation of aldehydes by chiral alk-2-enyl donors prepared from cheap and readily available optically pure ketones such as (-) - or (+) -menthone.
Our article : “Total Synthesis of Cyclomaltohexaose” describing the first total synthesis of Cyclomaltohexaose had been recognized as the most requested through CAS' information services via ChemPort during 2002. And CAS Science Spotlight sculptures were presented to Tomoya Ogawa of RIKEN and Yukio Takahashi of Daito Chemical. Some presentations about CAS Science Spotlight and Total Synthesis of Cyclomaltohexaose are described here. CAS Science Spotlight is one of free web service that represents most frequently requested scientific articles and interesting literatures. We had succeeded in a regio- and stereo-controlled synthesis of Cyclomaltohexaose via intramolecular cyclization of glucohexaosyl fluoride in 21 steps, 0.02% total yield starting from maltose octaacetate.