A novel Pd-catalyzed reaction of a 2-halo- or 2-trifloxy-l, 3-butadiene derivative with a soft nucleophile is developed. The reaction proceeds via an exo-alkylidene-π-allylpalladium intermedi-ate in a formal SN2' fashion to give an allenic compound exclusively. A variety of soft nucleophiles, such as malonates, phenoxides, and imides, are applicable to the reaction, and thus a wide range of functionality can be introduced to the products. The reaction is extended into an asymmetric counterpart and axially chiral allenes are prepared with up to 93% ee by the use of chiral palladium catalysts. A formal total synthesis of an insect pheromone is achieved using the Pd-catalyzed asymmetric reaction as a key step. The Pd-catalyzed reaction also enables to prepare axially chiral (allenylmethyl) silanes and allenylsilanes in optically active forms. Reactions of these silylallenes with appropriate electrophiles proceed via SE', pathways and the allenic axial chirality is efficiently transferred to stereogenic carbon centers in the SE', products.
Highly enantioselective cyclopropanation of styrene derivatives and diazoacetates was effectively catalyzed by ketoiminatocobalt(II) complexes. Addition of a catalytic amount of N-methylimidazole significantly accelerated the reaction and enhanced the enantioselectivity due to its coordination to the center cobalt atom of the complex as an axial ligand. Analysis of the transition states by the PM 3 (tm) method indicated that the olefin approached parallel to the cobalt-carbene bond with bisecting an O-Co-O angle. The reaction pathway of the cyclopropanation was analyzed by the density functional method to reveal that the axial donor ligand produced two prominent effects. One is that the activation energy for the formation of the cobalt carbene complex was reduced and that the activation energy for the cyclopropanation step was increased. The other is that the distance of the carbene carbon above the ligand plane was shortened during the cyclopropanation step. It was revealed that the carbene-carbon bond of the ketoiminatocobalt-carbene complexes is characterized as an extraordinary single bond based on the theoretical and FT-IR analysis. The key reactive intermediate of borohydride reduction catalyzed by Schiff base-cobalt com-plexes is proposed to be the dichloromethyl-cobalt hydride with a sodium cation, based on experimental and theoretical studies. It was revealed that chloroform is not the solvent but the reactant that activates the cobalt catalyst. It was found that a catalytic amount of chloroform effectively activated the present catalytic system to convert various ketones into the corresponding reduced product with a high ee in the THE solvent. Furthermore, the theoretical simulation of various axial groups in cobalt complex catalysts predicted that the cobalt-carbene complexes could be employed as efficient catalysts. The newly designed complexes generated from cobalt complex and methyl diazoacetate made it possible to catalyze the enantioselective borohydride reduction in a halogen-free solvent.
Spirocyclic scaffolds are embedded in many biologically active natural compounds, including candidates for medicines, perfumes and agricultural chemicals. Therefore, a development of efficient synthetic methods directed at those structures is strongly demanded. To this end, we have recently developed synthetic methodologies for two different spirocyclic frameworks, spiro[4.5]decanes and spirocyclic oxindoles, based on Claisen rearrangement. We have developed the Claisen rearrangement protocol by which bicyclic 2-(alkenyl) dihydropy-rans with functionality at C 4 can be transformed to spiro[4.5]decanes in good-to-excellent yields with excellent stereoselectivities. We applied this method to a concise total synthesis of several biologically active spirocyclic sesquiterpenes. Related Claisen rearrangement in (alkenyl)pyranoindole systems can be also achieved. Thus, a one-pot intramolecular Ullmann coupling/Claisen rearrangement sequence from 2-iodoindoles was found to provide spirocyclic oxindoles in good yields with excellent stereoselectivities. We applied this sequence to the synthesis of pyrrolidinoindoline alkaloids.
2-Bromo-1-alkenes have been recognized as one of useful functional groups for preparation of vinyl lithiums and vinyl Grignard reagents, for coupling partners in a wide range of transition metal-mediated coupling reactions, substrates of radical reactions, and precursors of a-haloke-tones. Selective elimination reaction of 1, 2-dibromoalkanes possessing aryloxy or acyloxy groups at the C 3 position into 2-bromo-1-alkenes under mild basic conditions was developed. Alkyne units are also one of the important functional groups for substrates of C-C coupling reactions. During our extensive investigation, the acidity enhancement of hydrogen at the C 1 position by oxygen-functional groups at the C 3 position was also observed. This observation indicated a new prospective synthesis of propargyl ethers from 1, 2-dibromoalkanes using DBU as a base. As application of these elimination reactions, total synthesis of biologically active natural products was accomplished.
Precision design of structure and function of silicon-containing oligomers and polymers is described based on the precise control of the reactivity and stereochemistry of silicon compounds. Firstly, conversion of oxy anion to carbanion was achieved by the aid of the ring-opening of silacy-clobutane derivatives by oxy anion, which was used to synthesize multi-block copolymers from epoxide and vinyl monomers. Secondly, synthesis of polycarbosiloxane was described based on newly found dehydrogenation reactions to give siloxane bonds from silane and silanol in the presence of various catalysts. Thirdly, stereo-chemical aspect of reactions of silicon compounds, and control of stereoregularity and optical activity of silicon-containing polymeric systems were described. Syndiotactic polysiloxanes was synthesized for the first time. Finally, structural control of polyhedral oligomeric silsesquioxanes was described. Cis sym cyclic tetrasiloxane was proved to be an important intermediate to form polyhedral oligomeric silsesquioxanes with various structures. A possible reaction mechanism was proposed for the formation of oligosilsesquioxane with controlled structure. Some applications of these compounds were also described.
The acid mediated carbon-carbon bond formation promoted by elimination of small molecule of carbon monoxide or hydrogen and the related reactions are discussed. The specific decarbonyla-tive arylation reactions of a-alkoxy- or a-oxocarboxylic acids with the aid of acidic mediator such as P2O5-MSOH or TFOH affording various arylated products are presented. Furthermore, the acid mediated dehydrogenafive formation of enol ethers or equivalents followed by crossed-aldol addition to activated benzaldehyde derivative or equivalents giving a, β-unsaturated carbonyl compounds or 1-alkoxy-2-alkylindenes is discussed. The elucidation of the structural requirements, the reaction routes, and the reaction mechanisms for these molecular transformations are described in detail. Some related reaction behaviors such as distinction in regiospecificity and dependence on acidic mediator of acid-mediated aroylation of γ- or δ-oxocarboxylic acids and intramolecular electrophilic aromatic substitution of a-alkylcinnamaldehydes affording 1-alkoxy-2-alkylindenes are also discussed.
The enantionselective addition of terminal acetylenes to aldehydes or ketones affords a direct access to optically active propargyl alcohols which are useful, versatile synthetic intermediates. This mini review focuses on the recent advances in zinc (II) and indium (III) salts-mediated asymmetric alkynylation on carbonyl compounds via in situ "catalytic" generation of metal acetylide.