Diazoketone cyclization

Diazoketone Cyclization onto a Benzene Ring 3,4-Dihydro-l(2H)-Azulenone... 

Serratose, et al., have succeeded in converting readily available lactone 361 to semi-bullvalene. The scheme, which involves no skeletal rearrangement, is based on diazoketone cyclization chemistry within an oxygenated cyclopentenyl derivative... 

A tandem cyclization-cycloaddition reaction was developed as a method for synthesizing polycyclic ring systems which involved a rhodium(II) acetate-induced diazoketone cyclization onto a neighboring carbonyl group to generate an ylide followed by 1,3-dipolar cycloaddition. Thus (208) has been transformed into the 8-substituted pyrrolizidone (209) <89JA645l). 

Another example of orthoester rearrangement for the construction of a quaternary center is given in the enantioselective synthesis of (-t)-valerane 148 [34]. In this synthesis, ii-(-)-carvone 149 is used as starting material. Rearrangement of allylic alcohol 150 afforded ester 151. Diazoketone cyclization is then followed by a ring enlargement affording the bicyclo[4.4.0]decane system (Scheme 6.22). 

Tandem cyclization-cycloaddition of diazoketones in the synthesis of some alkaloids 97F303. 

Preparation of the sulfur analogue involves as the first step cyclization of the terephthalic acid derivative 92. The acid is then converted to the acid chloride and this is allowed to react with diazomethane. Rearrangement of the resulting diazoketone (95) under the conditions of the Arndt-Eistert reaction leads to the homologated acid. 

The cyclization of phenolic diazoketones 246 to spirodienones 247 was reinvestigated with Rh2(Me3CCOO)4> Rh2(OAc)4 and Pd(OAc)2 as catalysts235 the yields were found to be better than with CuCl used in earlier studies. 

Intramolecular C/H insertion by copper-catalyzed decomposition of a-diazoketones provides a convenient cyclization procedure which is limited, however, to diazo compounds which allow energetically favorable realization of the transition state leading to the cyclized product. 

The Cu semicorrin complex (68a) has been successfully used as the catalyst for cyclization of alkenyl diazoketones, though the reactions of some substrates showed modest enantioselectivity (Scheme 74).276 Shibasaki et al. have successfully used the cyclization of diazoketone with Cu bis(oxazoline) (101) for the construction of the CD ring skeleton of phorbol.277... 

Two type la syntheses of (3-hydroxypyrroles have appeared. An aza-Nazarov cyclization of l-azapenta-l,4-dien-3-ones produced (3-hydroxypyrroles including 2,2 -bipyrroles <06EJO5339>. A second approach to a (3-hydroxypyrrole involved an intramolecular N-H insertion into a rhodium carbene derived from the decomposition of a diazoketone <06JOC5560>. On the other hand, the photochemical decomposition of the diazoketone led to pyrrolidin-2-ones. 

The reactions of A -BOC-protected a-amino acids 424 and diazomethane in the presence of iV-methylmorpholine-polystyrene and isobutyl chloroformate resulted in formation of diazoketones 425, which, on treatment with indium(lll) triflate, were cyclized to 4-substituted-tetrahydro-l,3-oxazine-2,5-diones 426 in high overall yields (Scheme 82) <2006TL7969>. 

When thiocarbonyl and ot-diazocarbonyl compounds are combined, acyl-substituted thiocarbonyl ylides 158 are generated from a nonisolable 3-acyl-1,2,4-thiadiazoline 157 (Scheme 8.36). In addition to giving acylthiiranes 159 and 1,3-dithiolanes 160, dipoles 158 can also 1,5-cyclize to produce 1,3-oxathioles 161. Acyl-thiocarbonyl ylides derived from diazoketones [e.g., HC(0)C(N2)R, R = Ph, f-Bu (219,220) 2-diazocyclohexanone (221)] produce 1,3-oxathioles [e.g., 162 (220), Scheme 8.36], while those derived from diazoesters (218,222,223) lead to thiiranes by 1,3-cyclization. Ylides derived from a-diazocarboxamides form 1,3-oxathioles (e.g., 163) and thiiranes (e.g., 159, R = f-Bu, R = NMePh, R = R" = Ph), depending on the nature of the substituents (220). A related 1,5-cyclization of an aminomethyl-thiocarbonyl ylide formed from dimethyl 3-anilino-2-diazobutanedioate was also reported (224). 

The equivalence of sulfur and oxygen in this ring system carries over to NSAIDs as well. Preparation of the sulfur analogue of isoxepac (6-4) starts with the alkylation of thiophenol (27-1) with benzyl chloride (26-1). Cyclization of the intermediate thioether (27-2) then affords the homothioxanthone (27-3). The carboxyl side chain is then extended by means of the Amdt-Eistert homologation reaction. The acid is thus hrst converted to its acid chloride by means of thionyl chloride. Reaction with excess diazomethane leads to the diazoketone (27-4). Treatment of that intermediate with silver benzoate and triethylamine leads the ketone to rearrange to an acetic acid. There is thus obtained tiopinac (27-5) [28]. 

Furanones have been prepared by treatment of y-ketoacids with acetic anhydride. Furanones have also been formed by hydrolysis and dehydrobromination of j8,y-dibromoacids (B-50MI31200). The furan-3(2//)-one system (164) has been prepared by intramolecular cyclization of the diazoketones (163) (74TL3073). Some natural 3(2//)-furanones are known furaneol (166), occurring in strawberries and pineapples, is obtained by acid or base treatment of the dihydroxydiketone (165) (73JOC123). 

The acid-catalyzed decomposition of diazoketones (226) gives rise to cations which then cyclize to 2-iminotetrahydro-l,3-thiazin-5-ones (227). On hydrolysis these lead to the corresponding 2,5-diones (228) (80KGS1327). 

The diazoketone (69) affords thioindoxyl (17) on treatment with hydrochloric acid286 unlike its oxygen analog, which can be obtained by cyclization of 70 (X = 0) with acid, thioindoxyl cannot be obtained by cyclization of the related compound (70) (X = S).286... 

In this context, it is worth mentioning that there is only one other, clear-cut example for the simultaneous occurrence of the acyl(silyl)carbene-to-acylsilene and the acylcarbene-to-silylketene rearrangement of an acylcarbene bearing a Si—Si substituent. Carbene 57, generated by photolysis of diazoketone 56 in benzene, isomerized to both 58 and 59 in about equal amounts44. While the acylsilene cyclized to 1,2-silaoxetene 60, the ketene was isolated and structurally characterized by X-ray diffraction analysis of the derived... 

In the event, iodolactonization of the carboxylate salt derived from the ester 458 afforded 459, and subsequent warming of the iodo lactone 459 with aqueous alkali generated an intermediate epoxy acid salt, which suffered sequential nucleophilic opening of the epoxide moiety followed by relactonization on treatment with methanol and boron trifluoride to deliver the methoxy lactone 460. Saponification of the lactone function in 460 followed by esterification of the resulting carboxylate salt with p-bromophenacylbromide in DMF and subsequent mesylation with methanesulfonyl chloride in pyridine provided 461. The diazoketone 462 was prepared from 461 by careful saponification of the ester moiety using powdered potassium hydroxide in THF followed by reaction with thionyl chloride and then excess diazomethane. Completion of the D ring by cyclization of 462 to the keto lactam 463 occurred spontaneously on treatment of 462 with dry hydrogen chloride. 

In contrast, in the photolysis of3,6-diphenylpyridazine-N-oxide 28 (R1 = R2 = Ph), a mixture of 3-benzoyl-5-phenylpyrazole 31 and 2,5-diphenylfuran 32 is formed. Diazoketone 29 (R1 = R2 = Ph) undergoes two competing reactions (i) thermal internal cyclization into the pyrazole 31 or (ii) photoinduced formation of a carbene leading to the final furan 32 (Scheme 12.9) therefore, the product distribution depends heavily on the reaction conditions. Thus, the formation of pyrazole 31 (75%) is favored over that of furan 32 (3%) by irradiation in acetone in a Rayonet reactor equipped with lamps irradiating at 350 nm. On the other hand, by irradiation with a Hanovia immersion lamp the yield of 31 decreases to 27%, whereas the yield of 32 increases to 67%. Moreover, the exclusive formation of the furan derivative 32 (43%) was observed by irradiation in the Rayonet reactor at low temperatures (—65 °C) [27]. 

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