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Two optional routes to β-phenylnaphthalene structure are developed by introducing α- and β-styryl groups onto different positions in the benzocyclobutene ring followed by ring enlargement.

An unexpected structural incongruity between coleophomones 1 and the reported structure of recently isolated natural product 2 was confirmed by total synthesis of key semi-synthetic derivative 3 and its positional isomer 4. In addition, possible mechanisms for the interconversion of expected structure 22 to observed compound 2 are postulated, some of which may have an important role in the biosynthetic origin and chemistry of these structurally unique natural products.

Base-promoted cyclocondensation of hindered nitrile oxides and cyclic diketones affords highly functionalized, sterically-encumbered isoxazole products in good yield. The mild reaction conditions (NEt3, EtOH) are tolerant to a wide variety of functionality and permit the preparation of precursors to complex polycycles typically inaccessible via direct, intermolecular carboncarbon bond forming reactions. The ability to effect the cyclocondensation reaction with a catalytic amount of amine points to the intermediacy of an ammonium enolate as a key reactive species. A convenient, single step preparation of crystalline, stable nitrile oxides from the corresponding oximes enhances the advantages of this methodology for the preparation of functionalized polycycles.

Various functionalized biaryls are accessible via a simple two-step process. Treatment of alkenylcyclobutenones with aryllithium provides ring-opened trienes, which are smoothly cycloaromatized under thermal conditions.

Stereospecific pinacol-type 1,2-shift of electron-rich heterocycles was achieved under organoaluminum-promoted conditions to afford optically pure ketones or alcohols possessing these heterocycles. The method was applied to the asymmetric formal total synthesis of indolmycin.

An efficient synthetic route to 3-(phenylsulfonyl)phthalides possessing a β- C -olivoside was developed by exploiting the regioselective [2+2] cycloaddition of benzyne with ketene silyl acetal. The compounds are useful in the total synthesis of the angucyclines, including aquayamycin.

A highly oxygen-functionalized cyclohexenone 2 , the AB ring fragment for the aquayamycin synthesis, was efficiently synthesized via stereoselective addition of allylzinc bromide to ketone 3a which, in turn, was available from the optically pure cyclohexane 1,2,3-triol derivative 5 .

In relation to the synthesis of the pradimicin–benanomicin antibiotics, a model study was carried out for introducing the disaccharide moiety. The glycosyl donor 2, prepared from d -glucose and d -xylose, was allowed to react with various glycosyl acceptors in the presence of Cp2HfCl2 and AgClO4. Also studied was the reactivity difference between the conformers of the trans-phenanthrendiol derivatives 12, 13 and 14.

The first total synthesis of aquayamycin (1) has been accomplished. The crucial steps include (1) the Hauser reaction between 3-(phenylsulfonyl)phthalide 3 and cyclohexenone 4 to make up the linear BCD tricycle, and (2) the intramolecular pinacol coupling of keto aldehyde 7 to the full tetracyclic framework.

[(C 6 H 5 ) 3 C] + [B(C 6 F 5 ) 4 ] − effectively catalyzes the alkylmetallation of alkynes by using the alkylzirconium species, which is generated by the hydrozirconation of alkenes.

Behavior of the compounds 2 with a Co-complexed enyne moiety was examined. When R in 2was a prim-alkyl group, the cyclization to give a cyclobutane proceeded in high yield, whereas, when R was bulkier, an interesting substitution involving a 1,2-shift was observed.

Allylzirconium species, generated by hydrozirconation of allenes, react with 1-iodoalkynes in the presence of methylaluminoxane (MAO) to give the substitution products of the iodide by an allyl group. Labelling study for 2-(iodoethynyl)naphthalene suggested that the reaction involves allylzirconation of iodoalkynes to generate an alkylidene carbenoid that undergoes 1,2-rearrangement.

Impressive changeover of the reaction course was observed in the rearrangement of styrylbenzocyclobutenol derivative 1. While the thermal reaction gave naphthalene 2, the base-promoted reaction gave the isomeric product 3 in high yield.

In relation to the total synthesis of the furaquinocins, stereoselective methylenation of chiral aldehyde 5 is described. The diastereoselectivity of epoxides 6a/6b is high when stabilized sulfur ylides are employed. A double stereo-differentiation phenomenon was observed for the aminosulfoxonium ylide 8: the selectivity with (S)-8 was 30:1, while 5:1 with (R)-8.

A regio- and stereocontrolled method for the allylmetallation of 1-alkynes is described. The allylzirconium species, generated by hydrozirconation of allenes, undergo regioselective addition to 1-alkynes in the presence of organoaluminum reagents among which methylaluminoxane (MAO) is particularly effective. © 1997 Elsevier Science Ltd.

A d - olivosyl donor in which the C(3) and C(4) hydroxyls are both protected by an extremely bulky group, t-BuPh2Si, undergoes aryl C-glycosidation in an α-selective manner, and the product configuration remains unchanged under various Lewis acid conditions. The features are rationalized by the ring flipping of the pyranoside ring (1C4) in the glycosyl donor and the C-glycoside product, due to the severe repulsion of the siloxy groups.

Use of NbCl 5 in the Sakurai reaction gave an unexpected outcome. Allylsilane reacted with aldehyde in 2:1-stoichiometry with concomitant formation of a cyclopropane ring. Mechanistic implications of this anomalous reaction related to C 4 H 7 + species are discussed based on the experimental and theoretical (ab initio) studies.

A concise total synthesis of BE-12406 A ( 3a ) was achieved. The key step was the selective O -glycosylation of naphthol 4 with l -rhamnopyranosyl fluoride 5 , employing Cp 2 HfCl 2 -AgClO 4 in fluorobenzene at −20°C in the presence of a hindered base 9 , affording O -glycoside 8 in good yield.

The SmI2-induced reductive intramolecular cyclization of an aldehyde and β-alkoxy acrylate was further investigated for the synthesis of polycyclic ethers having an angular methyl group. The cyclization produced 6,6- and 6,7-membered bicyclic ethers having a methyl group at C2 or C6 and C2 or C7 position, respectively.

Two- and four-carbon homologation of aldehyde is described, which is based on the AgClO4-catalyzed addition of zirconcene complexes, derived from hydrozirconation of 1-ethoxyethyne (1) and (Z)-1-methoxy-1-buten-3-yne (2) with Cp2Zr(H)Cl, followed by acidic hydrolysis.

Nucleophilic addition of alkenylzirconocene chloride [Cp 2 Zr(Cl)CH CHR] to aldehyde, which is ordinarily a slow reaction, is remarkably accelerated by a catalytic amount of AgClO 4 . The rate acceleration effect is also valid for the alkyl congener, Cp 2 Zr(Cl)R.

A new synthetic method of 1,3-diene by three-carbon elongation of aldehyde is described. 3-Trimethylsilyl-1-propenylzirconocene chloride ( 2 ), generated from 3-trimethylsilyl-1-propyne ( 1 ) and Cp 2 Zr(H)Cl, reacts with aldehyde in the presence of catalytic AgClO 4 and subsequent one-pot 1,4-elimination affords 1,3-dienes in high yields with excellent ( E )-selectivities.

An effective approach for introducing vineomycin-fridamycin-type side chain was developed. Tin-lithium exchange of arylstannane 5 followed by the reaction with chiral aldehyde 6 gave the desired adduct 7 . Total synthesis of (R)-(+)-fridamycin E was accomplished.

Ortho-metallation of anthracene derivative with alkyllithium is hampered by the preferential attack of the anion to the C(9) and/or C(10) positions. Use of n-BuLi-t-BuOK effected a clean and regioselective metallation at C(2) and subsequent reaction with Me3SiCl or Me3snCl afforded the corresponding arylsilane or arylstannane in high yields.

Stereospecific 1,2-rearrangement of epoxy silyl ethers in the presence of nucleophiles is described. The reaction affords 1,3-diols or corresponding mono-silylated ethers, which provides a route to establish three- or four-contiguous asymmetric centers in one step.

Semi-pinacol cyclization of compound 8 , having an acetal and an aldehyde substituent, was achieved by employing SmI2 and BF3·OEt2, leading to the highly stereoselective formation of cyclized product 9 . The vicinal diol in 9 is discriminated, so as to allow selective glycosylation for the synthesis of pradimicin–benanomicin antibiotics.

A synthetic route to a biologically active glycosyl flavonoid, astilbin ( 1 ), was developed. The tetra-benzyl ether 4 , derived from (+)-catechin, was glycosylated with the l -rhamnosyl donor 10 by using Cp 2 HfCl 2 –AgClO 4 , and subsequent oxidation of the C(4) position of the flavan skeleton followed by deprotection gave 1 .

First total synthesis of ravidomycin has been achieved, thereby establishing the relative and absolute stereostructure as 1.

Arynes are generated cleanly and rapidly by halogen-lithium exchange of ortho-haloaryl triflates with n-BuLi at −78 °C. [2+4]-Cycloaddition of α-alkoxyaryne with 2-methoxyfuran proceeded regioselectively (head-to-head) to afford 1,4,5-naphthalenetriols.

Upon treatment with lithium dialkylamide, 2-alkoxy-2-vinylbenzocyclobutenols undergo two-carbon expansion to give substituted naphthalene derivatives.

In the presence of Li-TMP and an aromatic aldehyde, benzocyclobutenone undergoes an unusual heterolytic C(1)C(4) bond fission, and subsequent reaction with the aldehyde gives, after acidic workup, isochroman-3-one in high yield.

Reductive pinacol-type rearrangement of chiral α-mesyloxy ketones was effected by organoaluminums (DIBAL in combination with Et 3 Al or Et 2 AlCl) leading to enantiomerically pure 2-aryl- or 2-alkenyl-1-propanols.

Nucleophilic addition to substituted γ- and δ-lactols with titanium reagents provides 1,4-syn and 1,5-syn diols in high stereoselectivity, which represents a new and simple method for the remote asymmetric induction.

Stereocontrol of C(2)-position of δ-lactones, related to Prelog-Djerassi lactone, is effected via acid-catalyzed cyclization of ketene dithioacetal having an internal OH group (thermodynamic control), which is also applicable to remote asymmetric induction.

First total synthesis of mycinamicin IV via mycinamicin VII is described. New glycosidation reaction using Cp 2 MCl 2 -AgClO 4 (M=Zr, Hf) was effectively applied to the selective introduction of β-D-mycinosyI and β-D-desosaminyl linkages.

All four diastereomere of chiral alcohol 2 with three contiguous chiral centers were stereoselectively prepared via diastereoselective addition of nucleophiles (crotyl metal or H-) to α-methyl-β,γ-unsaturated carbonyl compounds 1 .

A new method for the construction of quarternary carbon centers is reported, which is based on the Lewis acid-promoted 1,2-rearrangement of β,γ-epoxy alcohols giving α,α-disubstituted aldols stereospecifically in high yields.

Conformational effects on the reaction course were examined in organoaluminum-promoted pinacol-type rearrangement, using stereo-defined unsymmetrical β-mesyloxy alcohols as the probe, where combinational use of DIBAL-Et 2 AlCl achieved highly selective migration.

Stereoselective reduction α-chiral α-cyclopropyl ketones and α-cyclopropyl aldols is described. Introduction of trimethylsilyl (TMS) group to the α-position of cyclopropyls leads to virtually complete stereoselection to give the stereo-defined β-cyclopropyl alcohols and 2-cyclopropyl-1,3-diols.

Asymmetric (stereospecific) pinacol-type rearrangement of aryl or vinyl group in α-hydroxy methanesulfonates is promoted by Et3Al in CH2Cl2 at −78°C to afford optically pure α-aryl or α-vinyl ketones.

Preparation of 1-fluoro-D-desosamine derivative 1 and its glycosidation are described. A new activation system for glycosyi fluorides, Cp2 HfCl2-AgCIO4, enables highly efficient glycosidation of 1 .

Regio- and stereo-controlled formation of C-aryl β- d -olivoside linkage is achieved by the reaction of naphthol or anthrol derivatives with d -olivosyl fluoride. the reaction is efficiently promoted by Cp 2 HfCl 2 AgClO 4 and the bond formation occurs selectively at the ortho position of the phenolic hydroxyl. A short and stereoselective synthesis of the C-aryl glycoside sector of vineomycin B 2 is described.

Stereospecific 1,2-rearrangement of cyclopropyl group is described as an efficient route to stereo-defined α-cyclopropyl ketones and α-cyclopropyl aldols. Acceleration of the reaction by the introduction of trimethylsily (TMS) group to the α-position of cyclopropyl group is also noted.

Reduction of α-methyl-β,γ-unsaturated ketones with L-Selectride proceeded with high threo -selectivity to afford threo -β-methyl homoallylic alcohols of high enantio- and diastereomerical purities.

Optically pure α-methyl-β,γ-unsaturated ketones are synthesized by the Et3Al-mediated pinacol-type rearrangement where alkenyl groups migrate stereospecifically with complete retention of the olefin-geometry.

Highly enantio- and diastereo-controlled synthesis of chiral pheromone, eldanolide, was accomplished in both enantiomeric forms, via organoaluminum-mediated asymmetric pinacol-type rearrangement followed by stereoselective reduction.

The combination of Cp 2 MCl 2 -AgClO 4 , (M=Zr, Hf) is effective for the activation of glycosyl fluorides, which enables the highly β-selective glycoside formation of D-mycinose by performing the reaction in benzene.

Stereo-defined 2-vinyl-1,3-diols are synthesized by the reduction of aldol derivatives bearing α-trimethylsilylvinyl group at C(2) (LiBEt3H / THF, −78°C), which proceeds highly stereoselectively to give 1,2-syn isomer as the sole product.

Combination of Cp 2 ZrCl 2 AgBF 4 (molar ratio = 0.5 : 1) is highly effective in promoting rapid and high-yield glycosidation of tetra-O-benzyl-D-mannopyranosyl fluoride. Yields are excellent in all cases examined and high α-selectivity is achievable by the reaction in benzene at room temperature.