Transition metal-promoted reactions

Transition metal-promoted reactions have recently become important in the synthesis of the basic core structures of quinazolines and quinazolinones. While many of the examples below are not necessarily biologically relevant in and of themselves, they highlight important areas of development in the synthesis of these ring classes that can be employed in the future synthesis of compounds with greater biological significance. 

Wantanabe and co-workers used an intermolecular reductive N-heterocyclization approach to generate quinazoline. Treatment of 2-nitro benzaldehyde with palladium(II) and molybdenum(V) complexes as catalysts in the presence of carbon monoxide under high pressure generated quinazoline in 29% yield. 

Quinazoline derivatives were prepared by Fu and co-workers using an Ullmann-type coupling. Treatment of (2-bromophenyl)methylamine with benzamide in the presence of potassium carbonate and a copper(I) catalyst under thermal conditions in isopropanol gave the corresponding quinazoline in 87% yield. The authors also reported modest to good yields using several substituted (2-bromophenyl)methylamine and benzamide derivatives (not shown). 

Larksarp and Alper used a palladium(II) catalyzed cyclocarbonylation reaction to generate a series of more complex and biologically relevant 4(3 0- iuinazolinone derivatives. Compounds of this class, such as the mold metabolite crysogine Penicillium chrysogenum), have been shown to exhibit PTK inhibition and cholecystokinin inhibition as well as antimicrobial, anti-convulsant, anti-depressant and anti-inflammatory properties. Reaction of o-iodoaniline, a substituted ketenimine, and carbon monoxide with palladium(II) acetate and l,l -bis-diphenylphosphino-ferrocene (dppf) under thermal conditions gave the desired quinazolinone in near quantitative yield. In the same report, the authors showed that similar reactions could also be conducted with isocyanates and carbodiimides (not shown). 

Abdel-Jalil and co-workers used a novel copper(II)-catalyzed condensation reaction between anthranilamides and aryl, alkyl, and heteroalkyl aldehydes to generate the corresponding 4(3 -quinazolinones in excellent yields. In one example, treatment of anthranilamide with 2-furaldehyde gave the corresponding 2-substituted quinazolinone in 85% yield. The resulting compound could be used to readily access the antibiotic nitrofurquinazol in just a few short steps. 

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Transition Metal-promoted Reactions 9.07.2.3.1 Palladium-catalyzed reactions... 

In most cases the products obtain are derivatives of 1,3-butadiene. Although in this respect the reactions resemble the thermolyses of bicyclobutane, there are two major differences between these two classes of reactions. The first one lies in the reaction conditions. While the thermal reactions necessitate elevated temperatures and are characterized by high activation energies (see Section V.G) most of the reactions with transition metals occur very rapidly at room temperature. The second difference is in the stereochemistry of the reaction. While thermal reactions (be they concerted or not) generally follow the Wood war d-Hoffmann rules, transition metal promoted reactions give products with a different stereochemistry. These can be formally viewed as la + la processes. The following reactions illustrate this point (equations 95-97). Further labeling... 

Supportive evidence for the identity of intermediate 86 was also obtained from the transition metal promoted reaction of the corresponding diazo derivative 87 which furnished the same product " ... 

The addition of carbenes and carbenoids to imines and nitriles continues to be a popular approach to aziridines and 2//-azirines. These processes have been well reviewed by Deyrup (B-83MI101-01). Dichlorocarbene and other dihalocarbenes have been added to a wide variety of imines to provide dihaloaziridines. A recent example is shown in Equation (64), illustrating the use of phase-transfer conditions <93H(36)69i). The treatment of azides with excess dichlorocarbene results in the formation of the 2,2,3,3-tetrachloroaziridines (92TL2339). Presumably, the azide is converted by dichlorocarbene to the imidoyl dihalide RN=CC12 which reacts further with dichlorocarbene. Transition metal-promoted reaction of a-diazoesters with imines provides 2-(alkoxycarbonyl)aziridines [Pg.46]

Transition-Metal-Promoted Reactions of Unsaturated Hydrocarbons. IV. Reactions of Norbornenyl Complexes of Palladium(II) with Group V Donor Ligands, Olefins, 1,3-Dienes and 1,2-Dienes, E. Ban, R. P. Hughes, and J. Powell, J. Organometal. Chem., 69, 455 (1974). 

Wilczynski, R. Sneddon, L. G. Transition-metal-promoted Reactions of Boron Hydrides. 2. Synthesis and Thermolysis Reactions of Alkenyl-pentaboranes. New Synthesis of Monocarbon Carboranes. Inorg. Chem. 1981, 20, 3955-3962. 

It is the aim of this chapter to present in detail a few selected examples of useful organic transformations promoted by Group 4-11 (Ti-Cu) metals rather than to give a comprehensive listing of all possible transformations, as this information is available in several other excellent books. - The protocols are selected to demonstrate the most common oxygenation (addition of O atoms) or oxidation (removal of H atoms) pathways encountered in transition metal-promoted reactions of organic substrates. 

Pender, M. J. Wideman, T. Carroll, P J. and Sneddon, L. G. Transition metal promoted reactions of boron hydrides. 15." Titanium-catalyzed decaborane-olefin hydroborations one-step, high-yield syntheses of monoaUcyldecaboranes. J. Am. Chem. Soc. 1998,120, 9108-9109. 

Chan MC, Cheng KM, Ho KM, Ng CT, Yam TM, Wang BSL, Luh TY. Transition-metal-promoted reactions nickelo-cene-lithium aluminum-hydride. 19. A versatile desulfurization reagent. J. Org. Chem. 1988 53(19) 4466-4471. 

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