Transition Metal-Mediated Cyclization

Transition-metal-mediated cyclization reactions play an increasing role in the synthesis of heterocycles, as shown by furan syntheses catalyzed by Pd, Cu, and Au. 

Because of these interesting biological activities and the scarcity of materials from their natural sources through isolation, great emphasis has been placed on synthetic approaches toward the efficient construction of tetrahydropyrans. These approaches include the Prins and related cyclization reactions, the hetero-Diels-Alder cyclizations, radical cyclizations, transition metal mediated cyclizations, as well as more traditional methods such as epoxide-mediated cyclizations and oxa-conjugate addition reactions. 

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

Transition-metal mediated carbene transfer from 205 to benzaldehyde generates carbonyl ylides 211 which are transformed into oxiranes 216 by 1,3-cyclization, into tetrahydrofurans 212, 213 or dihydrofurans 214 by [3 + 2] cycloaddition with electron-deficient alkenes or alkynes, and 1,3-dioxolanes 215 by [3 + 2] cycloaddition with excess carbonyl compound120 (equation 67). Related carbonyl ylide reactions have been performed with crotonaldehyde, acetone and cyclohexanone (equation 68). However, the ylide generated from cyclohexanone could not be trapped with dimethyl fumarate. Rather, the enol ether 217, probably formed by 1,4-proton shift in the ylide intermediate, was isolated in low yield120. In this respect, the carbene transfer reaction with 205 is not different from that with ethyl diazoacetate121, whereas a close analogy to diazomalonates is observed for the other carbonyl ylide reactions. 

Numerous reactions of alkenyl(phenyl)iodonium salts leading to the formation of new C-C bond have been reported in the literature. The most important and synthetically useful reactions include the generation and subsequent cyclization of alkylidenecarbenes, alkenylation of carbon substrates via nucleophilic vinylic substitution, and transition metal-mediated coupling reactions. 

Synthesis of Alkaloids by Transition Metal-mediated Oxidative Cyclization... 

Metallacycles have been claimed to play pivotal roles in many transition metal-mediated multi-component coupling reactions [1]. For example, [2 -i- 2 -i- 2] alkyne cyclo-trimerization leading to benzenes - the Reppe reaction - has been considered to proceed via metallacyclopentadiene and elusive metallacycloheptatriene intermediates ("common mechanism ), while metallacyclopentenes have been proposed as intermediates for the [2 -i- 2 -i- 1] cyclo-coupling reactions of an alkyne, an alkene, and CO leading to a cyclopentenone (the Pauson-Khand reaction). A metallacyclic compound - which is defined here as a carbocyclic system with one atom replaced by a transition metal element - can be generally formed by oxidative cyclization of two unsaturated molecules with a low-valent transition metal fragment [2-4]. Alter-... 

A review for transition metal-mediated radical cyclizations f. Iqbal, B. Bhatia, N. K. Nayyar, Chem. Rev. 1994, 94, 519. 

Cyclopropane formation is also observed in transition-metal-mediated conversions of pent-4-enals. This reaction proceeds via oxidative addition of the metal to the aldehyde C —H group, decarbonylation and cyclization of the resulting homoallylmetal complex. 

Many methods for the preparation of both the a- and )8-C-glycosides have been developed, and new approaches are still appearing in the literature. This chapter covers the literature from the end of 1994 to early 1999, with other inclusions as deemed appropriate. Following the organization of earlier work [1], we select the mode reactivity of the anomeric center to define the category. The chapter discusses free radical chemistry. Cl anions, Wittig chemistry-cyclization chemistry, transition metal mediated chemistry, sigmatropic chemistry, and approaches based on cationic chemistry. The chapter focuses on the most recent and novel developments in the field, but all the relevant references are included whenever possible. 

A titanium-catalyzed hydroamination of 1,4-diynes and 1,5-diynes produces 1,2,5-trisubstituted pyrrroles in one synthetic step <04OL2957>. Treatment of 1,4-diyne 33 with titanium complex 34 led to the formation of pyrrole 35 via a hydroamination to an imino alkyne followed by an intramolecular 5-endo dig cyclization. Another transition metal-mediated pyrrole... 

Brain and Brunton reported one of the early palladium-catalyzed cyclizations, which provided benzimidazoles in moderate to high yield. In this study, Pd(PPh3)4 was used to catalyze the intramolecular -arylation of o-bromoamidines to afford variously substituted 1-alkyl or 1-phenyl-benzimidazoles. This report set the stage for additional investigations of transition-metal mediated A -arylation as a tactic for benzimidazole synthesis. 

Transition-metal-catalyzed functionalization of propargyfic alcohols and their derivatives (including cyclization reactions) 12S1131. Transition-metal mediated carbon—sulfur bond activation and transformations (including those in thiophene, benzothiophene, and dibenzo-thiophene derivatives) 13CSR599. 

Transition metal-mediated cycloaddition and cyclization reactions have played a vital role in the advancement and applications of modem synthetic organic chemistry. Rhodium-catalyzed cycloadditions/cyclizations have attracted significant attention because of their versatility in the transformations of activated and unactivated acetylenes, olefins, allenes, etc. These reactions are particularly valuable because of their ability to increase molecular complexity through a convergent and highly selective combination of acyclic components. In addition, these reactions allow for the preparation of molecules with chemical, biological, and medicinal importance with greater atom economy. Recent developments in rhodium-catalyzed cycloaddition and cyclization reactions are described in this section. 

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