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Hiroaki Ohno

Publications and source records attributed to Hiroaki Ohno.

33 records · Page 2Linked to original sources
PubMed2004

Palladium(0)-catalyzed synthesis of medium-sized heterocycles by using bromoallenes as an allyl dication equivalent.

We have developed a highly regio- and stereoselective synthesis of medium-sized heterocycles containing one or two heteroatoms via cyclization of bromoallenes bearing an oxygen, nitrogen, or carbon nucleophilic functionality in the presence of a palladium(0) catalyst and alcohol. In this reaction, bromoallenes act as an allyl dication equivalent, and the intramolecular nucleophilic attack takes place exclusively at the central carbon atom of the allene moiety. Interestingly, bromoallenes having a carbon nucleophile with a five-atom tether afford eight-membered rings with trans-configuration, while those having an oxygen or a nitrogen nucleophile give the corresponding cis-rings selectively. This is the first example that demonstrates the synthesis of medium-sized rings via cyclization of bromoallenes, and this reaction provides a very useful method for a catalytic synthesis of seven- and eight-membered heterocycles without using high dilution conditions.

Journal Article↗
PubMed2004

Palladium(0)-catalyzed stereoselective cyclization of allenenes: divergent synthesis of pyrrolidines and 3-azabicyclo[3.1.0]hexanes from single allenenes.

Two novel palladium(0)-catalyzed cyclizations of allenenes are described. Treatment of allenenes such as N-(1-alkyl-2,3-butadienyl)-N-allylsulfonamide with an aryl halide and K(2)CO(3) in the presence of a catalytic amount of Pd(PPh(3))(4) in dioxane affords 2,3-cis-pyrrolidines in a stereoselective manner. In sharp contrast, cyclization of the same allenenes using catalytic Pd(2)(dba)(3) x CHCl(3) in the presence of allyl methyl carbonate in CH(3)CN leads to stereoselective formation of a 3-azabicyclo[3.1.0]hexane framework in moderate yields.

Journal Article↗
PubMed2004

Evaluation of scopadulciol-related molecules for their stimulatory effect on the cytotoxicity of acyclovir and ganciclovir against Herpes simplex virus type 1 thymidine kinase gene-transfected HeLa cells.

Herpes simplex virus type 1 thymidine kinase (HSV TK) is involved in both antiherpetic therapy and cancer gene therapy with acyclovir (ACV) and ganciclovir (GCV). Enhanced sensitivity to these drugs is advantageous in their clinical use. In the present study, scopadulciol (SDC) and its related compounds were evaluated for their stimulatory effect on the cytotoxicity of ACV and GCV by determination of selective toxicities against HSV TK-expressing HeLa cells. Although SDC remarkably potenciated the cytotoxicity of ACV and GCV, the other tested compounds showed only weak selectivity, except for compound 34.

Abietanes↗
PubMed2004

Stereodivergent synthesis of chiral 2-alkenylaziridines: palladium(0)-catalyzed 2,3-cis-selective aziridination and base-mediated 2,3-trans-selective aziridination.

Whereas treatment of the allylic mesylates of N-protected 2-alkyl-4-amino-(E)-2-alken-1-ols with sodium hydride in DMF yields exclusively the corresponding thermodynamically less stable 2,3-trans-2-alkenyl-3-alkylaziridines, exposure of the methyl carbonates of N-protected 2-alkyl-4-amino-(E)-2-alken-1-ols to a catalytic amount of Pd(PPh(3))(4) in THF or 1,4-dioxane affords predominantly the corresponding thermodynamically more stable 2,3-cis-2-alkenyl-3-alkylaziridines. The kinetically favored trans-selective aziridination would be attributed to the allylic 1,3-strain in aza-anionic intermediates. The conformational analysis of the sterically highly congested 2-alkenylaziridines thus obtained is also presented.

Aziridines↗
PubMed2003

Samarium(II)-promoted radical spirocyclization onto an aromatic ring.

Samarium(II)-mediated spirocyclization onto an aromatic ring was achieved by the reaction of methyl 4-(4-oxoalkyl)benzoates with SmI(2) in the presence of i-PrOH and HMPA, yielding methyl 1-alkyl-1-hydroxyspiro[4.5]dec-6-ene-8-carboxylates in moderate to high yields. Utilizing this chemistry, spiro[3.5] and -[5.5] systems, and sterically congested spiro[4.5] systems, were easily synthesized. For the successful conversion, appropriate activation of the aromatic ring has proven to be extremely important: while an ester or amide functionality on the aromatic ring can promote the spirocyclization, a sulfonamide substituent causes ortho cyclization.

Journal Article↗
PubMed2003

Radical cyclization by ipso substitution of the methoxy group: considerable effect of HMPA on samarium-mediated cyclization.

Alkyl radicals generated by treatment of thiocarbamates of conformationally favorable 3-alkyl-3-arylpropan-1-ols with tris(trimethylsilyl)silane and AIBN efficiently undergo intramolecular ipso substitution of the methoxy group, yielding the corresponding cyclized products. In contrast, either conformationally favorable or flexible 1-arylalkan-3- or 4-ones easily cyclize into five- or six-membered condensed rings by treatment with SmI(2) via ketyl radical intermediates. The addition of HMPA as cosolvent dramatically changes the cyclization mode of the SmI(2)-induced reaction, and the para-cyclization products are exclusively formed. This "HMPA effect" can be rationalized by the strong chelating ability of HMPA with the samarium atom.

Journal Article↗
PubMed2002

A highly cis-selective synthesis of 2-ethynylaziridines by intramolecular amination of chiral bromoallenes: improvement of stereoselectivity based on the computational investigation.

The base-mediated intramolecular amination of bromoallenes having an axial chirality is described. The treatment of (4S,aR)-4-alkyl-4-[N-(arylsulfonyl)amino]-1-bromobuta-1,2-dienes with NaH in DMF affords 2,3-cis-2-ethynylaziridines in good to excellent selectivity (2,3-cis:trans = 92:8-99:1). The reaction of (4S,aS)-bromoallenes with NaH/DMF also gives 2,3-cis-2-ethynylaziridines selectively (79:21-91:9). These experimental results have been rationalized by B3LYP density functional calculations together with the 6-31+G(d) basis set and the Onsager solvation model. The transition structures for cis-aziridine formation of both (4S,aR)- and (4S,aS)-bromoallenes in DMF are favored over the corresponding trans transition structures by 4.35 and 1.41 kcal/mol, respectively. Furthermore, the calculations predicted that a less polar solvent gives higher cis selectivity for (4S,aS)-bromoallenes. In fact, improvement of the cis selectivity to 99:1 has been realized by using a less polar solvent such as THF. The cyclization of bromoallenes bearing a beta- or gamma-amino group also affords four- and five-membered azacycles in a highly cis-selective manner.

Journal Article↗
PubMed2002

Synthesis of allenes from allylic alcohol derivatives bearing a bromine atom using a palladium(0)/diethylzinc system.

A general and efficient synthesis of allenes using a palladium(0)/diethylzinc system is described. Treatment of mesylates or trichloroacetates of (E)- or (Z)-2-bromoalk-2-en-1-ols with diethylzinc in the presence of a catalytic amount of palladium(0) affords allenes bearing an aminoalkyl, alkyl, or aryl substituent(s) in good to high yields. No transfer of chirality from the stereogenic center carrying the mesyloxy group to the allene was observed.

Journal Article↗
PubMed1998

Reactions of N-Arylsulfonyl-2,3-cis- and N-Arylsulfonyl-2,3-trans-3-alkyl-2-vinylaziridines with Organocopper Reagents: Importance of 2,3-cis-Stereochemistry in Controlling Regio- and Stereoselectivity.

Although reactions of 2,3-trans-N-arylsulfonyl-3-alkyl-2-alkenylaziridines with organocopper reagents give a mixture of two or three products, the corresponding 2,3-cis-isomers provide a highly efficient route to synthetically important nonracemic (E)-allylamines. It is also found that the reaction proceeds via the well-known anti-S(N)2' pathway.

Journal Article↗
PubMed1997

Palladium(0)-Catalyzed Isomerization Reactions of Aziridines Bearing an alpha,beta-Unsaturated Ester Group: A Thermodynamic Preference for Chiral Alkyl (2E)-4,5-cis-4,5-Epimino-N-(alkyl- or arylsulfonyl) 2-Enoates over the Other Three Stereoisomers.

Palladium(0)-catalyzed reactions of five sets of four stereoisomeric 4,5-epimino-N-(methanesulfonyl) or -N-(arylsulfonyl) 2-enoates reveal that 4,5-cis-(2E)-isomers are thermodynamically more stable than other isomers, in accord with calculations. A highly stereoselective synthesis of (E)-alkene dipeptide isosteres having the desired stereochemistries from unwanted stereoisomeric 4,5-epimino-N-(arylsulfonyl) 2-enoates is also presented.

Journal Article↗