In contrast to the very large number of special methods applicable to syntheses in the heterocyclic series, relatively few general methods are available. The 1,3-dipolar addition offers a remarkably wide range of utility in the synthesis of five-membered heterocycles. Here the “1,3-dipole”, which can only be represented by zwitterionic octet resonance structures, combines in a cycloaddition with a multiple bond system – the “dipolarophile” – to form an uncharged five-membered ring. Although numerous individual examples of this reaction were known, some even back in the nineteenth century, fruitful development of this synthetic principle has been achieved only in recent years.

1,3-Dipolar Cycloadditions. Past and Future†

Asymmetric 1,3-Dipolar Cycloaddition Reactions

Einer sehr grosen Zahl spezieller Synthesewege in die heterocyclische in die Reihe steht ein nur bescheidener Satz an Aufbaumethoden von allgemeiner Verwendbarkeit gegenuber. Eine erstaunliche Anwendungsbreite bei der Synthese funfgliedriger Heterocyclen kommt der 1.3-Dipolaren Addition zu. Dabei vereinigt sich der nur mit zwitterionischen Oktett-Grenzformeln wiederzugebende „1.3-Dipol” mit einem Mehrfachbindungssystem, dem „Dipolarophil”, in einer Cycloaddition zum ladungsfreien funfgliedrigen Ring. Wenngleich die Kenntnis zahlreicher Einzelbeispiele bis ins vorige Jahrhundert zuruckreicht, gelangte das Syntheseprinzip erst in den letzten Jahren zu fruchtbarer Entfaltung.

1.3‐Dipolare Cycloadditionen Rückschau und Ausblick

We synthesized a new class of bifunctional catalysts bearing a thiourea moiety and an amino group on a chiral scaffold. Among them, thiourea 1e bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be highly efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins. Furthermore, we have developed a new synthetic route for (R)-(-)-baclofen and a chiral quaternary carbon center with high enantioselectivity by Michael reaction. In these reactions, we assumed that a thiourea moiety and an amino group of the catalyst activates a nitroolefin and a 1,3-dicarbonyl compound, respectively, to afford the Michael adduct with high enantio- and diastereoselectivity.

Enantio- and Diastereoselective Michael Reaction of 1,3-Dicarbonyl Compounds to Nitroolefins Catalyzed by a Bifunctional Thiourea

Recent Advances of Catalytic Asymmetric 1,3-Dipolar Cycloadditions

The Reactions of Primary Nitroparaffins with Isocyanates1

On the Thermal Dissociation of Organic Compounds. (1) The Urea Linkage (Diphenyl-urea in Fatty Acids)

(1) The rate constants and the activation energies of the thermal dissociation of symdimethylurea, asym-dimethylurea and asymphenylethylurea were determined. (2) It was demonstrated that the substituents have great influence on the dissociation reaction.

On the Thermal Dissociation of Organic Compounds. II. The Dissociation of the Urea Linkage in Sym-dimethylurea, Asym-dimethylurea and Asym-phenylethylurea in Butyric Acid

(1) The rate constant and the activation energy of thermal dissociation of phenylcarbaminic acid phenylester in butyric acid are determined. (2) It has been made clear on the basis of reaction mechanism that dissociation of ester linkage requires larger activation energy than that of urea linkage.

Toshio Hoshino

Papers

The Reactions of Primary Nitroparaffins with Isocyanates1

On the Thermal Dissociation of Organic Compounds. (1) The Urea Linkage (Diphenyl-urea in Fatty Acids)

On the Thermal Dissociation of Organic Compounds. II. The Dissociation of the Urea Linkage in Sym-dimethylurea, Asym-dimethylurea and Asym-phenylethylurea in Butyric Acid

On the Thermal Dissociation of Organic Compounds. III. The Dissociation of Ester Linkage in Phenylcarbaminic acid phenylester in Butyric acid.

Über die synthese von alkoxy- und oxy-carbazole