Yasuhiro Torisawa

Interesting reaction of the indanone oximes under Beckmann rearrangement conditions

Attempted Beckmann rearrangement of the 6-methoxyindanone oximes in conventional conditions resulted in the formation of the two kinds of unexpected products: 2-sulfonyloxyindanone and the dimeric product. Related rearrangement was also observed in the reaction with RhCl-trifluoromethansulfonic acid system.

Glycosylation of sialyl acetates with a novel catalyst combination: Bismuth triflate and BF3·OEt2 system

A combined system of bismuth triflate [Bi(OTf)(3)] and boron trifluoride etherate (BF(3).OEt(2)) in dichloromethane is an efficient promoter for the glycosylation of N-acetylneuraminic acid derivatives. The co-existence of two acid catalysts such as Bi(OTf)(3)-BF(3).OEt(2) or Bi(OTf)(3)-PPA is confirmed to be essential for obtaining high yields of glycosylation products with p-nitrobenzyl alcohol, which also turned to be superior to those reported previously.

Beneficial effect of cesium salts on Pd-catalyzed hydroxycarbonylation.

A Pd(0)-catalyzed hydroxycarbonylation of the aryl bromide was effectively carried out in the presence of some Cs salts such as cesium carbonate, cesium bicarbonate, and cesium acetate in wet DMF solution. For the understanding of their function, an oxy-coordinated intermediate arising from a Cs oxygen-Pd interaction has been postulated, which is likely to be responsible for related Cs assisted catalytic processes.

Some aspects of NaBH4 reduction in NMP

In our solvent optimization study of NaBH(4) reduction, NMP was found to enhance the reactivity. A chemoselective debromination of the bromide and sulfonates can be attained in the new borohydride reagent system: NaBH(4)-LiOTf-NMP. This mixed system worked as an alternative to NaBH(3)CN and Bu(3)SnH for the S(N)2 type displacement of alkylbromide and sulfonate. Also mentioned is an expedient reduction of an azide group into amine by NaBH(4) in NMP without any additive, which offers a convenient protocol for the direct transformation of halides into amines via azide in one flask. Some examples of other reductions were also presented.

Modulation of the Cs2CO3-promoted catalytic amination by a crown ether

The catalytic addition of 18-Crown-6 in some Cs2CO3-promoted amination of triflates and bromides was beneficial to improve sluggish reaction with suppression of the unwanted side products. The protocol was useful for the preparation of chlorinated aryl piperazines from phenol derivatives.

A study on the conversion of indanones into carbostyrils.

We have surveyed the utility of Beckmann rearrangement for the conversion of indanones into carbostyrils. Initial attempts at the conversion of 6-methoxy indanone oxime under classical conditions resulted in the formation of the two unusual products: 2-sulfonyloxyindanone and the dimeric product. This unusual rearrangement was also observed by the treatment of some metal triflates species. Further investigation has led to the development of reliable conditions starting from oxime mesylate (not oxime tosylate), in which some strong Lewis acid catalyst (ZrCl(4)) was employed in either a conventional or non-conventional solvent system. The advantage of the new protocol is highlighted by the simple work up and direct isolation of the product in 65% isolated yield.

Investigation on the coupling reactions of aryltriflates with aromatic amines: Selection of the metal catalyst

Abstract A simple and effective coupling reaction of aryl triflates with aniline derivatives in the presence of palladium catalyst is described, which appears to be a general and useful protocol for the preparation of functionalized arylamines starting from phenols.

Synthetic study on the unique dimeric arylpiperazine: access to the minor contaminant of aripiprazole

The dimeric derivative of aripiprazole was synthesized via the two notable synthetic technologies as a key step: (1) efficient aldehyde bis-arylation by Bi(OTf)(3) and (2) facile Wynberg amination at room temperature. The synthesis has established the structural identity with the minor contaminant sometimes present in Aripiprazole.

An efficient conversion of 5-nitroisatin into 5-nitroindole derivative

Our process research on OPC-35564 revealed that a mixed borohydride reducing agent (ZrCl4/NaBH4) in DME (Itsuno system) afforded a rapid and direct conversion of N-alkyl-nitroisatin into nitroindole nucleus. Comparison with other reducing agents indicated the superiority of the present system and the key function of ZrCl4. For the manipulation of base-labile isatin, a useful procedure for its N-alkylation using Cu2CO3 is also presented.

A Novel Thiolate Mediated Cyclization to OPC-15161

Abstract An efficient synthetic route to OPC-15161 ( 1 ) was developed via novel pyrazine ring closure promoted by a lithium thiolate anion. The key intermediate ( 4 ) was prepared in a one-pot procedure by treating the methyl ester ( 2 ) with a lithium arylthiolate. This protocol does not require a free acid intermediate and thus can establish the shortest route to pyrazine dioxide skeleton from tryptophan ester derivatives. In the present transformation, lithium arylthiolates could behave like aluminium arylthiolates, and not like lithium alkylthiolates that often cleave esters to the corresponding acids. One-pot reactions that involve lengthy multiple steps in a single flask are of significant importance in contemporary organic synthesis. Utilization of a catalytic or stoichiometric promoter which can facilitate several transformations is a key to the success of such reactions. In this paper, we would like to disclose an interesting one-pot transformation discovered in our process research, which offered us novel information on the reactivity of metal thiolates. Main feature of our one-pot process is a merged deprotection-cyclization sequence.