Suzuki Noriyuki

Background: Developing environmentally benign processes, such as organic reactionsconducted in water, is desired from the view of sustainable technology. Concerning the palladiumcatalyzedborylation reactions of aryl halides in water, only a few examples have been reported. Objective: This study aimed to develop efficient methods for palladium-catalyzed borylation reactionsof aryl halides in water, not only increasing product yields but also extracting products withless organic solvents. Methods: We adopted polymer surfactants, such as diblock copolymers that consist of poly(Nisopropoylacrylamide)and a hydrophilic segment, and a poly(ethylene glycol)-based polymer thatconsists of poly(ethylene glycol) chain and 4-chloromethylbenzyl moiety. Results: Reactions using these polymers gave the borylation products in significantly higher yieldsthan that in pure water. The efficiency of the extraction process for the products from the reactionmixtures was evaluated, indicating that the polymer micelles enabled separation processes with lessorganic solvent. Conclusion: Applying polymer surfactants increased the product yields in Pd-catalyzed borylationof aryl halides, and it enabled the extraction of the products from the aqueous reaction mixture moreefficiently.

With a number of biologically active members, 2‐aroylchromones are valuable synthetic targets. A direct route towards 2‐aroylchromones from 2‐(methylsulfonyl)chromones and aldehydes via NHC‐catalyzed C‐C bond formation was developed. Yields of the synthesized 2‐aroylchromones were up to 85%. Chromones with angioprotective or antibacterial properties were easily synthesized using the method developed. Additionally, the synthetic utility of the afforded chromones was demonstrated by using them to synthesize the anticancer compound wrightiadione and analogues of it.

Pd complexes covalently tethered on thermoresponsive polymer catalysed coupling reactions in water.

A molecular editing strategy to construct quinoxalinones from chromones and benzimidazolylidene N-heterocyclic carbenes (NHCs) was developed. The C2 atoms of the chromones were incorporated into the quinoxalinones via ring expansion of the NHCs.

Abstract: Ruthenium-catalyzed olefin metathesis reactions were conducted in water with thermoresponsiveblock copolymers forming micelles. The block copolymers were prepared by living radicalpolymerization and consisted of a thermo-responsive and hydrophilic segments. The formersegment included poly(N-isopropylacrylamide) or poly(N,N-diethylacrylamide), and the latterpoly(sodium 4-styrene sulfonate), poly(sodium 2-acrylamido-2-methylpropanesulfonate) orpoly(ethylene glycol). Homometathesis, cross-metathesis and ring-closing metathesis reactions proceededto afford the products in moderate to good yields. Extraction efficiency from the reactionmixture was also studied.

The soil is a rich ecosystem where many ecological interactions are mediated by small molecules, and in which amoebae are low-level predators and also prey. The social amoeba Dictyostelium discoideum has a high genomic potential for producing polyketides to mediate its ecological interactions, including the unique ‘Steely’ enzymes, consisting of a fusion between a fatty acid synthase and a chalcone synthase. We report here that D. discoideum further increases its polyketide potential by using the StlB Steely enzyme, and a downstream chlorinating enzyme, to make both a chlorinated signal molecule, DIF-1, during its multi-cellular development, and a set of abundant polyketides in terminally differentiated stalk cells. We identify one of these as a chlorinated dibenzofuran with potent anti-bacterial activity. To do this, StlB switches expression from prespore to stalk cells in late development and is cleaved to release the chalcone synthase domain. Expression of this domain alone in StlB null cells allows synthesis of the stalk-associated, chlorinated polyketides. Thus, by altered expression and processing of StlB, cells make first a signal molecule, and then abundant secondary metabolites, which we speculate help to protect the mature spores from bacterial infection.

Reactions of five-membered zirconacycloalkynes and zirconacyloallenes with Cp₂Zr(H)Cl gave five membered zirconacyloallenes without work-up such as protonolysis and hydrogenolysis.

A few kinds of thermoresponsive diblock copolymers have been synthesized and utilized for palladium-catalyzed coupling reactions in water. Poly(N-isopropylacrylamide) (PNIPAAm) and poly(N,N-diethylacrylamide) (PDEAAm) are employed for thermoresponsive segments and poly(sodium 4-styrenesulfonate) (PSSNa) and poly(sodium 2-acrylamido-methylpropanesulfonate) (PAMPSNa) are employed for hydrophilic segments. Palladium-catalyzed Mizoroki–Heck reactions are performed in water and the efficiency of the extraction process is studied. More efficient extraction was observed for the PDEAAm copolymers when compared with the PNIPAAm copolymers and conventional surfactants. In the study of the Sonogashira coupling reactions in water, aggregative precipitation of the products was observed. Washing the precipitate with water gave the product with satisfactory purity with a good yield.

Five-membered metallacycloallene compounds, 1-zirconacyclopenta-2,3-dienes 1, derived from but-1- en-3-ynes 2 and low-valent zirconocene, reacted with esters and isocyanates. Reactions of 1 with car- boxylic esters such as ethyl acetate and methyl benzoate resulted in the formation of alkynyl ketones after hydrolysis, albeit in low yields, and diethyl carbonate gave alkynyl esters in moderate yields. Insertion of isocyanates such as phenylisocyanate to the ZreC bond of 1 afforded an alkynyl amide when 1 had substituents at the 2,4-positions (1a), while the zirconium complexes 1 that had silyl groups at the 2,5-positions, 1b and 1c, gave dienyl amides after hydrolysis. These reactions involved C]O insertion into the Zr-Csp3 bond in 1. It is likely that the insertion afforded seven-membered 1-oxa-2- zirconacyclohepta-3,4-diene intermediates first, whilst the reaction of 2,5-disilyl-1-zirconacyclopenta- 2,3-dienes 1b-c with isocyanates formed five-membered 1-oxa-2-zirconacyclopent-3-ene intermediates. Additional CeC bond formation reactions of these intermediates via transmetallation to copper salts followed by addition of allyl halides furnished allylated products.

L-Proline was covalently tethered on thermoresponsive ionic block copolymers that formed micelles in aqueous solutions. The block copolymers consisted of a poly(N-isopropylacrylamide) (PNIPAAm) segment and an anionic or cationic polymer segment. These copolymers exhibited lower critical solution temperature (LCST) behavior at ca. 35–40 °C, and achieved thermal stimuli-induced formation and dissociation of micelles. The copolymer generated micelles in aqueous solution at higher temperature, where a catalytic aldol reaction proceeded with high diastereo- and enantioselectivities. The micelles dissociated at lower temperature to form a clear solution such that the products could be efficiently extracted from the aqueous reaction mixture. Extraction of the aldol product with organic solvent from the aqueous solution of the anionic copolymer was more efficient than from the nonionic copolymer solution.

Palladium-catalyzed Mizoroki-Heck reactions were carried out in water using thermoresponsive polymer micelles. The micelles were generated from thermoresponsive block copolymers consisting of a poly(N-isopropylacrylamide) (PNIPAAm) segment and a hydrophilic segment such as nonionic poly(ethylene glycol) (PEG) (2) and anionic poly(sodium p-styrenesulfonate) (PSSNa) (9). These copolymers exhibited lower critical solution temperature (LCST) behavior at ca. 40-50 deg and showed thermal stimuli-induced formation and dissociation of micelles. The copolymers formed micelles in aqueous solution at higher temperature, where catalytic reactions proceeded. At lower temperature, the micelles dissociated to form a clear solution, enabling efficient extraction of the products from aqueous reaction mixture. In the presence of these copolymers, palladium complexes catalyzed the coupling reactions between aryl iodides and alkene compounds inside the hydrophobic micelle cores in water under relatively milder conditions. Extraction of the products from the aqueous solution of 2 or 9 was found to be efficient enough in comparison with conventional surfactants.

Five-membered metallacycloallene compounds, 2,5-disubstituted 1-zirconacylopenta-2,3-dienes were prepared from (E)-1,4-trialkylsilylbut-1-en-3-ynes in good yields. The structures of these compounds were determined by X-ray diffraction study. Contrary to our previous study on 2,4-disubstituted 1-zirconacylopenta-2,3-dienes, which gave alkynyl alcohols by the reaction with ketones after hydrolysis, the 2,5-bis(trialkylsilyl) complexes reacted with ketones to afford allenyl alcohols. Reactions with a nitrile gave a pyrolle compound probably via the formation of seven-membered 1-aza-2-zirconacylcohepta-3,4,7-triene compounds. When the (E)-1,4-bis(trialkylsilyl)but-1-en-3-ynes were treated with titanium isopropoxide/n-butyllithium followed by reaction with nitriles, the corresponding alkynyl ketones were obtained.

The cyclotrimerization of terminal alkynes, such as ethyl propynoate, arylacetylenes, and alkylacetylenes, catalyzed by phosphine-free [IrCl(cod)]2 is induced by a catalytic amount of tin(II) chloride in 1,4-dioxane to afford 1,2,4- and/or 1,3,5-trisubstituted benzenes. Terminal α,ω-diynes also undergo the cyclotrimerization with monoynes to form bicyclic benzene derivatives. cod=1,5-cyclooctadiene.

Reaction of η2-iminozirconocene chloride complexes with trimethylsilylethynyl lithium yields the corresponding five-membered aza-zirconacycloallenoids, which were also obtained from in situ generated zirconocene with alkynyl imines.