Cycloaddition of diazoalkanes

Dipolar cycloadditions of diazoalkanes to pyridazines 98JHC1187. 3(2//)-Pyridazinones in modem synthetic andmedicinal chemistry 98JHC1075. 

Despite a similar reversal of regioselectivity is also observed in the cycloadditions of diazoalkanes 226, 238, and 231 to methoxycarbonyl methylenecyc-lopropane 4 (Scheme 39), the result cannot be ascribed only to steric effects in this case [61]. A difference in dipolar character of dipoles 226 and 231 is also able to justify the result. 

The 1,3-dipolar cycloaddition of diazoalkanes 276 and nitrile oxides 279 to isothiazole dioxides 275 provides an easy entry into fused bicyclic isothiazole systems 277 and 280, respectively <06JHC1045>. The adducts from 4-bromoisothiazole (R1 = Br) are labile and undergo spontaneous debromination to form the aromatic bicyclic pyrazolo-isothiazoles 278... 

Moffett and coworkers203 reported the synthesis of several 4-/3-D-ribofuranosylpyrazoles, such as 284(a-c), by 1,3-dipolar cycloaddition of diazoalkanes to the alkenic C-glycosyl compound 283, followed by dehydrogenation of the resulting pyrazolines. In view of the known biological activities of several nucleosides containing the... 

Scheme 8. 1,3-Dipolar cycloaddition of diazoalkanes 34 onto methyl 2-chloro-2-cyclopropyl-ideneacetate (1-Me) [26a, 33]...

In the context of stereoselective organic synthesis, diastereofacial-selective cycloadditions of diazoalkanes and diazoacetates with functionalized alkenes has attracted some attention. 3,4-Disubstituted cyclobutenes were studied as dipolar-ophiles by the groups of Gandolfi and co-workers (113) and Martin and co-workers (114). The transition state structures of the cycloaddition of diazomethane with cis-3,4-dimethylcyclobutene was investigated theoretically by DPT methods (113a). 

The first effective enantioselective 1,3-dipolar cycloaddition of diazoalkanes catalyzed by chiral Lewis acids was reported in the year 20(X) (139). Under catalysis using zinc or magnesium complexes and the chiral ligand (R,/ )-DBFOX/Ph, the reaction of diazo(trimethylsilyl)methane with 3-alkenoyl-2-oxazolidin-2-one 75 (R = H) gave the desilylated A -pyrazolines (4S,5R)-76 (R =Me 87% yield, 99% ee at 40 °C) (Scheme 8.18). Simple replacement of the oxazohdinone with the 4,4-dimethyloxazolidinone ring resulted in the formation of (4R,5S)-77 (R = Me 75% yield, 97% ee at -78 °C). 

Cycloaddition of diazoalkanes to diazabicyclo[2.2.0]hexanes (134) and subsequent extrusion of nitrogen affords diazatricyclo[3.2.0.02,4]heptanes (135) that are easily valence-isomerized to novel dihydrodiazepines (136) (84TL297). 

A practicable strategy to provide access to chiral pyrazolidine-3-carboxylic acid (16) makes use of asymmetric dipolar cycloaddition of diazoalkanes to u,p-unsaturated carboxylic acid derivatives. For this purpose a chiral auxiliary of the alkene component is used, e.g. Op-polzer s1166 1671 (lf )-2,10-camphorsultam.t164l As shown in Scheme 7, by reaction of (tri-methylsilyl)diazomethane (41) with /V-( aery I oy I )cam p h ors u 11 am (42), the AL(4,5-dihy-dropyrazoline-5-carbonyl)camphorsultam (43) is obtained. Reduction of 44 with sodium cyanoborohydride leads to A-(pyrazolidine-3-carbonyl)camphorsultam (45) as the 35-dia-stereoisomer (ee 9 1) in 65 to 80% yields.[164] The camphorsultam 45 is then converted into the methyl ester 46 by reaction with magnesium methylate without racemizationj1641... 

Cycloaddition of diazoalkanes with thiocarbonyl compounds occurs usually in the regiochemistry derived from a thiophilic addition of the carbon end of the dipole to sulfur, yielding a 1,3,4-thiadiazoline (1). 

RC=CKWG) yields 2,4-di-EWG-substituted pyrroles in the presence of copper catalyst but 2,3-di-EWG-substituted pyrroles in the presence of a phosphine catalyst.74 The 3 + 2-cycloaddition of diazoalkanes to (6 )-3-p-tolylsulfinylfuran-2(5//)-one produces diastereoisomeric pyrazolines in almost quantitative yield and with des >98%. (g) The sulfinyl group is responsible for the complete control of the n-facial selectivity in all these reactions.75 The Rh(II)-catalysed intramolecular 1,3-dipolar cycloaddition reaction of diazoamides (57) with alkenyl and heteroaromatic n -bonds yields pen-tacyclic compounds (59), via the ylide (58), in good to excellent yields and in a (g) stereocontrolled manner (Scheme 15).76... 

Cycloaddition of diazoalkanes to 6-6 bonds was among the first reactions tested on the carbon cages41 and affords isolable fullerene-fused pyrazolines as primary adducts. Photochemically induced extrusion of N2 from the latter yields 6-6-closed methanofullerenes having the functionalized bond embedded in a cyclopropane substructure, whereas the thermal process affords 6-5 open homofullerenes in which a methylene group is bridging the open junction between a six- and a five-membered ring.15-17... 

Stanovnik B, Jelen B, Turk C, Zlicar M, Svete J (1998) 1,3-dipolar cycloadditions of diazoalkanes to pyridazines. Asymmetric 1,3-dipolar cycloaddition of azomethine imines derived from diazoalkane-pyridazine cycloadducts. J Heterocycl Chem 35 1187-1204... 

Stanovnik B (1991) 1,3-dipolar cycloadditions of diazoalkanes to some nitrogen containing heteroaromatic systems. Tetrahedron 47 2925-2945... 

The cycloaddition of diazoalkanes to alkynes gives pyrazoles the use of stannyl alkynes ° produces tin derivatives of the heterocycle (cf. 4.1.6), for use in subsquent electrophilic ipio-displacements, or in palladium(0)-catalysed couplings. Aryl-diazomethanes can be generated in situ, from tosylhydrazones, for formation of pyrazoles. ... 

Not covered in this section are cyclopropanations that involve initial 1,3-dipolar cycloadditions of diazoalkanes to give pyrazolines, followed ring contraction and nitrogen extrusion. 

Reduction of a,p-unsaturated y-lactones to furanes (1,262). Pelletier et al. have developed a general method for conversion of 2(5H)-furanones (1) into substituted furanes (4). The method involves cycloaddition of diazoalkanes, diazo esters, and diazoketones, followed by decomposition to alkylated 2(5H)-furanones (3). The final step involves reduction with diisobutylaluminum hydride. 

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