荒井 秀

A simple and facile method for the cleavage of carbon-oxygen bonds promoted by niobium pentachloride(V) is described. Excellent yields and regioselectivities were observed with various alkyl aryl ethers to give the phenols. NMR studies revealed the formation of monoaryloxy niobium salt(V), and a neighboring-group effect may play a significant role in the regioselectivity. © Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

(Chemical Equation Presented) A new type of furan-iminium cation cyclization was developed and used to construct the ABC ring of manzamine A. The cyclization proceeded at the 2-position with complete regio- and stereoselectivity to give a spiro-center. The product was efficiently converted to the highly substituted core structure of manzamine A. © 2006 American Chemical Society.

Facile access to optically active pyrroloindoles by Fischer-type pyrroloindole synthesis is investigated. The reaction using chiral hydrazines prepared from commercially available chiral amines proceeded with diastereoselective cyclization (up to 70% de), and a short-step conversion of the cycloadducts to (-)-desoxyeseroline and pyrroloindole alkaloids was achieved. © 2005 The Japan Institute of Heterocyclic Chemistry.

An efficient homocoupling of imines to give vicinal diamines promoted by low-valent niobium, generated by treatment of NbCl5 with zinc powder, is described. The desired products were obtained in good to excellent yields. Dihydroisoquinoline derivatives also gave the coupling products with good diastereoselectivities (D,L/meso). Optical resolution of the racemic octahydrobiisoquinolines was achieved and their complexes with Cu1 used in the catalytic asymmetric oxidative coupling of β-naphthols. © Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Phase transfer catalysts including onium salts or crown ethers transfer between heterogeneous different phases and catalytically mediate desired reactions. Chiral non-racemic phase transfer catalysts are useful for reactions producing new stereogenic centers, giving chiral non-racemic products. Recent developments in this rapid expanding area will be presented.

Friedel-Crafts acylation catalyzed by niobium pentachloride with silver salt is described. Aromatic compounds with Ac2O or Bz2O were smoothly converted into the corresponding ketones in good to excellent yields. This system was also applied to the Sakurai-Hosomi reaction using acetals. The reaction proceeded quite rapidly to give the desired products in excellent yields. © 2005 Elsevier Ltd. All rights reserved.

We have recently completed the total synthesis of nakadomarin A utilizing furan-iminium cation cyclization, that is, intramolecular vinylogous Mannich reaction of furan. In this time, further application of this reaction to the synthesis of manzamine A was investigated. We expected that 6/6/5 tricyclic core of manzamine A would be constructed by furan-iminium cation cyclization between spiro iminium cations 1 and 2-furyl group connected to A ring with 1 or 2 carbon unit. Firstly, two cyclization precursors, 12 and 19, were prepared. From spirolactam 5, C1 unit and 2-furyl group were introduced to give furyl ketone 7 by carbonylative Stille coupling. Then deprotection and 1,2-reduction of enone gave secondary alcohol 10. Following protection of alcohol and reduction of lactam gave hemiaminal 12. On the other hand, C2 unit and 2-furyl group were introduced to 5 stepwisely. Wittig reaction of 5 gave exo olefin 13 which was diastereoselectively hydrogenated after deprotection of PMB to give 15. Then the ester 15 was converted to 2-furyl ketone 16 via Weinreb amide. After the protection of carbonyl group of ketone, hemiaminal 19 was obtained in similar protocol as above. Then, furan-iminium cation cyclization was examined. Both 12 and 19 cyclized regioselectively at 2-position of furan under mild acidic conditions. Furthermore, the stereochemistry of spiro center was completely controlled to give the ABC ring system of manzamine A with correct stereocenters. In conclusion, we have developed the new strategy of furan-iminium cation cyclization. This methodology would be effective in construction of carbon flameworks. Total synthesis of manzamine A using this strategy is now under investigating.

A simple and convenient method for the differentiation of alkoxy groups on aromatic rings is described. Niobium(V) is found to possess a strong Lewis acid property to transform alkyl arylethers smoothly to the corresponding phenols in high yields. The excellent regioselectivity was also observed in dialkoxy benzene derivatives under mild conditions.

A catalytic asymmetric Michael reaction promoted by new chiral quaternary ammonium salts is described. The products are obtained with moderate ee (up to 75% ee), and the enantioselectivity is strongly dependent on both the substituents on the aromatic rings and the ammonium moiety in the catalysts. © 2004 Pharmaceutical Society of Japan.

A new palladium-catalyzed cyclization of N-alkenyl-o-haloanilines with selective isomerization of a double bond followed by 5-endo cyclization was developed and used to synthesize fused indoles.

Various (2S,3S)-23-bisarylmethoxy-1,4-butanediols 3a-h were synthesized from L-(+)-tartrate through bisallylether 12. Protection of the primary alcohol as an allyl ether was essential for selective deprotection in the presence of reactive arylmethyl ethers.

Catalytic asymmetric Darzens reaction of haloamides is described. A new and easily-prepared bis-ammonium salt derived from BINOL acts as an effective phase-transfer catalyst and efficiently promotes the reaction to give the desired epoxides under quite mild conditions with up to 70% ee. © 2004 Elsevier Ltd. All rights reserved.

A simple method for the diastereoselective synthesis of racemic 1,2-diol mediated by low-valence niobium generated in situ is described. A 1,4-dioxane-toluene solvent system was found to be essential to achieve higher selectivities and to prevent other reactions of pinacols, such as deoxygenation and acetal formation. Aromatic aldehydes and ketones were converted to the corresponding pinacols with up to 97 and 85% de, respectively. © 2004 Pharmaceutical Society of Japan.

The one-pot (three steps) synthesis of α-diazo-β-hydroxyesters from tosyl chloride under phase-transfer catalysis is described. The catalytic asymmetric aldol reaction between a diazoester and aldehydes was also investigated and gave moderate to good enantioselectivity. © 2003 Elsevier Ltd. All rights reserved.

Since manzamine B (1) have been isolated from Okinawan marine sponge Haliclona sp. By Higa and co-workers in 1987, its pentacyclic structure involving large membered rings have been attractive as a synthetic target. While its interesting biological activities, such as cytotoxicity against P388 mouse leukaemia cells (IC_<50> 6μg/mL) and antitumor activity, have been reported, complete survey and further investigation have been prevented due to its limited availability. Herein, we report our synthetic approach of 1. Initially, we set the compound 7 as a key intermediate. In order to obtain 7 as an optically active form, asymmetric Diels-Alder reaction between 8 and aminodiene (9) using chiral-Cr-Salen complex was studied. After screening to reaction conditions, we have realized that 7a was obtained in 30% yield with up to 88% ee using carbamate-type aminodiene (9a). Amide-type aminodiene (9d) gave 7d in 37% with up to 81% ee, respectively. Next, construction of C-ring was investigated. Alkylation of formyl group of 7d, readily available by deprotection of N-allyl group with Pd (0), proceeded by Peterson reaction in 80% yield. After conversion of silyl enol ether to the corresponding ketal (23d), removal of N-chloroacetyl group was accomplished in pyridine under reflux conditions. Further transformation is currently under investigation.

The catalytic asymmetric Michael reaction of a glycine Schiff base was demonstrated using new PTCs and moderate to good ee's were achieved (up to 77% ee). © 2002 Elsevier Science Ltd. All rights reserved.

The development of the highly diastereoselective catalytic synthesis of glycidic acid derivatives via Darzens reaction is described. The reaction of α-chloroesters and amides with aromatic aldehydes smoothly proceeds in the presence of a quaternary ammonium salt as a phase-transfer catalyst to give the corresponding cis and trans desired products in satisfactory yields, respectively. © 2002 Elsevier Science Ltd. All rights reserved.

The [4+2]cycloaddition reaction utilizing trimethylsilylketene with 1,3-diaza-1,3-dienes smoothly proceeded to give the desired cycloadducts, 4(3H)-pyrimidinones, in moderate to high yields.

Catalytic isomerization of alkynes to allenes under phase-transfer catalyzed conditions is described. Commercially available quaternary ammonium salt such as tetrahexylammonium bromide acts as a very effective promoter to accelerate the reaction under mild conditions.

The catalytic asymmetric alkylation reaction of α-fluorotetralones promoted by a chiral quaternary ammonium salt derived from cinchonine under phase-transfer catalyzed conditions was described. The reaction proceeded smoothly to give the desired products with up to 91% ee. This methodology provides a practical protocol for the preparation of optically active fluoro compounds on a large scale.

An asymmetric cyclopropanation reaction was developed using chiral quaternary ammonium salts as the phase-transfer catalyst (PTC). The reaction smoothly proceeded to give the desired bicyclic compounds with complete stereocontrol in the presence of a catalytic amount of chiral quaternary salts as the PTC, which are derived from readily available chiral amines, with up to 83% ee under mild reaction conditions.

Catalytic asymmetric Darzens reaction promoted by a chiral phase- transfer catalyst derived from cinchonine is described. The desired α,β- epoxy ketones were obtained by use of α-chloro acyclic and cyclic ketones as substrates with moderate to high enantiomeric excesses under mild reaction conditions. This methodology can be quite an effective protocol for practical asymmetric synthesis.

Catalytic asymmetric Darzens reaction using cyclic α-chloro ketones promoted by chiral quaternary ammonium salts as a phase-transfer catalyst proceeded smoothly under mild reaction conditions to afford the desired products with reasonable enantioselectivities at room temperature.

Treatment of cyclic or acyclic α-haloenones with various carbon nucleophiles involving active methylene functions afforded the corresponding dihydrofurans in a stereoselective manner with good to high yields. This reaction system can provide a general and practical methodology for the construction of dihydrofuran rings.

Enantioselective synthesis of α,β-epoxysulfones by the Darzens reaction was achieved under phase-transfer catalyzed conditions. The reaction of chloromethyl phenylsulfone with various aromatic aldehydes smoothly proceeded in the presence of a catalytic amount (10 mol %) of chiral quaternary ammonium salt derived from quinine with KOH at room temperature to afford the desired coupling products in good yield with up to 81 % ee.

2-Alkyl-1,4-naphthoquinones were smoothly transformed to the corresponding epoxides in moderate to good yields with good enantioselectivities (up to 76% ee) under mild reaction conditions by use of a catalytic amount of chiral quaternary ammonium salts derived from quinidine as a phase-transfer catalyst.

Asymmetric epoxidation of a,b-unsaturated ketones with H2O2 was developed using a chiral quaternary ammonium salt as the phase-transfer catalyst. A catalytic amount of N-[4-(iodo)benzyl]cinchoninium bromide, easily prepared from cinchonine, was effective in the asymmetric epoxidation for producing the corresponding desired products with up to 92% ee under mild reaction conditions.

The catalytic asymmetric Homer-Wadsworth-Emmons reaction promoted by quaternary ammonium salts derived from cinchonine as a phase-transfer catalyst is described. Treatment of the prochiral ketone 1 with phosphonates under mild reaction conditions afforded the corresponding desired products in moderate enantiomeric excess.

The catalytic asymmetric Darzens condensation promoted by the quaternary ammonium salt (PTC A) derived from cinchonine as a phase-transfer catalyst is described. Treatment of phenacyl chloride with various aldehydes under mild reaction afforded he corresponding desired in good yield with good to moderate enantiomeric excess.

The catalytic and enantioselective hydrophosphonylation of a cyclic imine, namely the 3-thiazoline 1, is described. We have discovered a highly efficient enantioselective de novo approach to the pharmaceutically interesting 4-thiazolidinylphosphonate 2 using either titanium or lanthanoid chiral catalysts, which gives excellent enantiomeric purities (up to 98%ee) and high chemical yields.

Various asymmetric rare earth complexes have been prepared from rare earth metal trichlorides such as YCl3, LaCl3, PrCl3, NdCl3, SmCl3, EuCl3, GdCl3, TbCl3 and YbCl3, dilithium (R) binaphthoxide, NaOH and H2O. The optical purities of nitroaldols obtained using these rare earth complexes as an asymmetric catalyst have been highly dependent on the size of rare earth metals. The application to a catalytic asymmetric synthesis of (S)-metoprolol, a β1-selective β-blocker, has been also achieved. © 1993.