荒井 孝義

A catalytic asymmetric aldol reaction of alkenyl trichloroacetates with aldehydes was achieved using dibutyltin dimethoxide and BINAP (.) silver(I) complex as catalysts in a mixed solvent consisting of THF and MeOH. Various optically active beta-hydroxy ketones were diastereoselectively obtained not only from aromatic and alpha,beta-unsaturated aldehydes but also from an aliphatic aldehyde with good enantioselectivity up to 92% ee. (c) 2006 Elsevier B.V. All rights reserved.

Barium hydride promoted regioselective dimerization and cross-coupling reactions of 2-cycloalken-1-ones were achieved in the presence of HMPA or DMPU as a Lewis base. The cross-coupling reaction between 2-cyclopenten-1-one and chalcone derivatives followed by intramolecular cyclization provides bicyclic 1,5-diketones, which have a norbornane skeleton, regio- and stereospecifically in moderate to high yields.

A tandem cross-coupling reaction of ketones with aldehydes has been achieved using barium hydride or isopropoxide as a promoter, in which barium enolates are generated in situ and then three successive reactions (aldol reaction-beta-elimination-Michael addition) follow; this one-pot process is effective for obtaining symmetrical 1,5-diketones in good yields.

A catalytic allyl-transfer reaction from tertiary homoallylic alcohols to aldehydes was achieved using dibutyltin oxide as a catalyst in toluene under reflux conditions. Various secondary homoallylic alcohols were prepared in high yield (up to 99%). When beta-alkylated tertiary homoallylic alcohols were used, branched products were exclusively obtained.

Immobilisation of multicomponent asymmetric catalysts has been achieved utilizing soluble polymers and dendrimers containing BINOL ligands. A novel approach based on the use of '' catalyst analogue'' helps to position the ligands suitably on the polymer backbone. Utilizing metal-bridged polymers, a simple and efficient method for immobilisation without the need for a polymer support has also been realized. Heterogeneous Al-Li-bis(binaphthoxide) and mu-oxodititanium complexes thus obtained have been used as catalysts for the asymmetric Michael addition and the asymmetric carbonyl-ene reactions respectively. The catalysts displayed high activity affording the corresponding products with high enantiomeric excesses. In many cases, the catalysts could be recovered and reused.

The first chiral isoxazoline ligands bearing spiro skeleton are developed. The spiro bis(isoxazoline) ligands (SPRIXs) are readily synthesized from diethyl malonate via double intramolecular nitrile oxide cycloaddition as a key step. The complex of (M, S, S)-R-SPRIX and Pd(OCOCF3)(2) promoted the catalytic asymmetric Wacker-type cyclization of alkenyl alcohols to give optically active cyclic ethers for the first time. Furthermore, starting from dialkenyl alcohol, the enantioselective tandem cyclization via oxy-palladation was achieved with up to 95% ee. Asymmetric ligands other than SPRIXs promote neither the Wacker-type reaction nor the tandem reaction.

Synthesis of two kinds of new bis(isoxazoline) ligand, achiral 2,2'-bis(isoxazolinyl)propane and (R)-2,2'-bis(isoxazolinyl)-1,1'-binaphthyl bearing an axial chirality is described. Both of the bis(isoxazoline) ligands accelerated the Pd(II)-catalyzed Wacker-type cyclization of alkenyl alcohol. The isoxazoline ligands were found to be essential to promote the cyclization.

Heterobimetallic complexes function as both a Brφnsted base and a Lewis acid, making possible a variety of new asymmetric catalyses. Among them, ALB [AlLibis(binaphthoxide)] complex is an effective catalyst for asymmetric Michael reactions, tandem Michael-aldol reactions, and hydrophosphonylations of aldehydes. Herein we describe the applications of these reactions to practical catalytic asymmetric syntheses of several bioactive compounds. 1) Practical catalytic asymmetric synthesis of strychnos alkaloids The key Michael reaction promoted efficiently by ALB (0.3mol%) and KO/Bu (0.27mol%) in the presence of activated MS4A gave 2 in 98% yield and 99%ee. The Michael adduct 2 was converted to the tricyclic compound 9 using a Fisher indol synthesis and an amide coupling as key steps. Finally a first catalytic asymmetric total synthesis of 20-deethyl tubifolidine has been achieved through a key cyclization of 9 using DDQ. We hope to reveal our catalytic asymmetric total synthesis of (-)-tubifolidine, being currently under investigation, at the meeting. 2) Practical catalytic asymmetric synthesis of a prostaglandin derivative The three-component coupling product 10 was synthesized using a key tandem Michael-aldol reaction promoted efficiently by ALB (10mol%) in 86% yield and 91%ee, before the conversion to the enone 11. After recrystallization, optically pure 11 was transformed to the enone 14 through a hydrosilylation, a stereoselective reduction, and an aldol condensation via titanium-enolate, as key steps. Finally 11-deoxy-PGF_<1α> has been efficiently synthesized through a key asymmetric epoxidation of 14 using TBHP catalyzed by La-BINOL complex.