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The desired products are obtained together with the esters which result from the acyl transfer (for example Ph-CO-S-Me or Oct-CO-O-Pcp).

Under the influence of Mc2A1C1, ene-reaction of 2-(alkylthio)allyl silyl ethers readily proceeds with a wide range of aldehydes to afford the corresponding γ-hydroxy carbonyl compounds as their enol silyl ethers with high threo-preference as well as excellent (Z)-selectivity.

Different from lithium dialkylcuprates, Cu(II) catalyzed conjugate addition of Grignard reagents to allylic esters of α,β-unsaturated carboxylates has been effected in the presence of TMS-Cl, and the resulting allyl silyl keteneacetals further undergo rearrangement to afford 2-allyl 3-alkyl carboxylic acids in good yields.

A highly enantio-selective ene reaction was developed on the bases of charility transfer. Under the influence of Me 2 AlCl, the reactions of various aldehydes with ( S )-3-( tert -butyldimethylsiloxy)-2-(ethylthio)-1-butene which was easily prepared from ( S )-ethyl lactate afforded the optically active adducts in high ee.

The taxane family is one of the most challenging synthetic targets due to their unique carbon skeleton coupled with the highly potent anticancer activities of a congener, taxol. We have developed a powerful methodology based on Lewis acid mediated direct eight-membered-ring cyclization for taxane B ring that offers a general route for natural taxane synthesis. The methodology provides simultaneous solution for the following three of the most difficult problems for taxane synthesis.1) construction of the highly strained eight-membered B ring2) stereoselective installation of the C-9 and C-10 oxygen functionalities3) stereocontrol of the endo conformation.

In the presence of Lewis acid 2-(alkylthio)crotyl silyl ethers(1) react with aldehydes to give anti or syn adducts with high selectivity, depending on the geometry of 1. Further, on using TiCl4. E-adducts are produced, whereas Z selectivity is observed in the other Lewis acid promoted reactions.

A highly enantioselective synthesis of anthracycline precursors (1a and 10) was accomplished through a chirality-transfer ene reaction

Under the chelation conditions the title compounds reacted with α-benzyloxyaldehyde to afford syn diol exclusively. Further, three contiguous diastereomeric centers were constructed with high stereoselectivity by using ( E ) or ( Z )-crotyl silyl ether. This methodology was applied to the stereoselective synthesis of brassinolide side chain.

Lewis acid-mediated intramolecular cyclization of the dienol silyl ether or enol silyl ether and the acetal for medium-sized ring formation is described. Seven-, eight-, and nine-membered ring cyclization proceed in fairly good yields.

Copper catalyzed conjugate addition of Grignard reagents to enones was effected with high 1,4-diastereoinduction and was used for the preparation of taxane precursors.

Dimethylaluminum chloride-mediated [3 + 2] cycloaddition of methyl 2-phenylthiocyclopropyl ketone and enol TBDPS or TIPS ethers proceeds highly diastereoselectively to afford functionalized cyclopentanes in good yields.

The crystal structure of (1S,3S)-3-acetyl-5-methoxy-3-methylthio-1,2,3,4-tetrahydronaphtalene-1,8-diyl dibenzoate contains two independent molecules. These molecules have a similar conformation except for the dihedral angles between the aromatic ring and the benzoyloxy group linked to it, witch differ by a relative rotation of -160 o . The absolute configurations of the two citral centres C8 and C10 are established as S and S

The X-ray analysis of the title compound, C 20 H 28 O 4 , revealed a chair-boat-like conformation of the eight-membered ring which makes the whole molecule endo and the relative stereochemistry C1R * , C9 * and C10R *

Use of organoaluminum reagents induces ene-like reactions of enol silyl ethers with aldehydes, and enols having bulky silyl groups selectively afforded syn adducts.

Allyl sulfides containing a siloxy or hydroxy group at appropriate positions were successfully converted by two methods into two types of allylsilanes with almost complete stereo- and regiocontrol. In one method, an allyllithium was generated from the siloxy compound after which the silyl group migrated from oxygen to the carbanionic site. The reaction of 4-[[(trimethylsilyl)oxy]methyl]-3-methyl-2-cyclohexenyl phenyl sulfide with lithium di-tert-butylbiphenylide (LDBB) led to an exclusive formation of (1R * ,2R * )-2-methyl-2-(trimethylsilyl)-3-cyclohexene-1-methanol. The second method involved the silylation of an oxyanion-carbanion

N-Acylated 4-piperidone was prepared in good overall yield through an initial formation of the imine from the reaction of α′-aminomethylated enol silyl ether with an aldehyde followed by cyclization effected with an acid anhydride. The latter cyclization reaction seems to proceed preferentially through a boat-like transition state to give the piperidone having exo substituent.

A stereoselective ene reaction of aldimines with 2-(alkylthio)allyl silyl ethers was developed. Under the influence of Lewis acids, N-acylimine or geminal biscarbamates reacted with a (Z)-2-(methylthio)allyl silyl ether to afford syn adducts in >94% selectivity

In the presence of Me 2 AlCl, reactions of the title compounds with a variety of aldehydes proceeded with high efficacy of chirality transfer to give the corresponding optically pure ene adducts, which could be converted to the γ-lactones, e.g., rove beetle pheromone.

A-Ring fragment of taxol (2), α-hydroxy aldehyde 1, was enantioselectively prepared by using asymmetric dihydroxylation of enol silyl ether of the parent aldehyde.

The title reaction gives predominantly o-substituted anilines via rearrangement and opens the access to ortho-aminophenols.

By utilizing the characteristic features of vinylsulfides, 2- (alkylthio) allyl silyl ethers were designed as efficient ene substrates, and their use led to exploration of general carbonyl and imine ene reactions. By using 3- (alkylthio) -2-siloxyallyl acetates, a useful [3 + 2] cyclopentane annulation methodology was developed. Further, a tandem C-C bond formation/cleavage methodology was also designed.

Formal total synthesis of coriolin has been accomplished on the basis of a [3+2] cycloaddition reaction of a vinylsulfide with 3-(methylthio)-2-siloxyallyl cation. A five-membered vinylsulfine as a C ring unit was prepared in five steps from commercially available compounds. The first [3+2] cycloaddition reaction gave the BC ring intermediate, which was then converted into a bicyclic vinylsulfide in three steps. The construction of the A ring by the second [3+2] cycloaddition reaction followed by two-step-conversion afforded the tricyclic enone (30% overall yield from isobutyronitrile) which has previously been synthesized and converted into coriolin.

Enantioselective synthesis of a taxol C-ring fragment containing an allylsilane moiety is described. Diastereoselective [4 + 2] cycloaddition of the pyrone with ( R )- t -butylbenzyl vinyl ether followed by appropriate transformations gave a mixture of two regioisomeric cyclohexenyl sulfides, which was converted to the title compound with almost complete diastereo- and enantioselectivities by treating with Li and 4,4′-di- t -butylbiphenyl followed by quenching with chlorotrimethylsilane.

A new synthetic method for functionalized cyclopentanones was developed on the basis of a [3+2] cycloaddition reaction of a 1-(methylthio)-2-siloxyallyl cationic species and olefins. Allyl acetates 1a and 1b, which are the precursors of the allyl cationic species, are easily prepared in three or four steps from commercially available compounds. Under the influence of EtAlCl2 or AlCl3, 1a or 1b reacted with various kinds of olefins such as enol ethers, vinyl sulfides, styrenes, and trialkylolefins to afford the corresponding cyclopentanones in good yields. It is noteworthy that the sterically more hindered regioisomer was predominantly formed in every case. Furthermore, the reactions of 1b with vinyl sulfides exhibited surprisingly high stereoselectivity, which can be rationalized by the six-membered transition state models involving an orbital interaction between the sulfur atom of the vinyl sulfide and the α-carbon of the allyl cation.

In order to clarify the biosynthetic pathway of C6-C2 unit compounds containing salidroside, cornoside, and rengyosides A and B in oleaceous plants, 13C-labeled putative precursors, 4-hydroxyphenylethanol, salidroside and cornoside, were prepared.

To examine the biosynthetic pathway from secologanin to three types of secoiridoid glucosides characteristic of oleaceous plants, synthesis of two respective stereoisomers at C-8 of 8, 10-epoxysecologanin and -secoxyloganin was established and their deuterium-labeled analogues were prepared.

Artificial taxoids were synthesized and subjected to evaluation of their ability of multi-drug resistance reversing and antitumor activities. While the taxoid 4 could not increase cellular accumulation of vincristine in multi-drug resistant tumor cells, the C4-hydroxy analog 15 showed significant effect. However, these compounds showed weak activities on growth inhibition of cancer cells.

An efficient synthetic method for (-)-coriolin has been developed on the basis of a [3+2] cycloaddition reaction of a 1-(methylthio)-2-siloxyallyl cationic species and vinylsulfides. An enantiomerically pure C-ring unit was prepared through optical resolution of five-membered allyl ester 6b using a lipase. The first [3+2] cycloaddition reaction of C-ring unit (S)-7 gave bicyclic ketones 8 and 9, which were easily converted into vinyl sulfide 11. Stereoselective construction of the A-ring was achieved by the second [3+2] cycloaddition reaction of the BC-ring unit. New methods for introduction of the oxygen functional groups to the triquinane skeleton were also developed for the last stages of the total synthesis. Thus, the C7 hydroxyl group was introduced by epoxidation of dienol silyl ether 17, and stereocontrolled construction of the spiro epoxide moiety was accomplished on the basis of a Darzens-type reaction.