Dipolar Cycloadditions of Diazoalkanes

The reactive intermediates A and C could be so short-lived that they cyclize extremely fast. They certainly could cyclize so fast that the trans-configuration of the 2-methyl-2-butenoic acid moiety by and large is carried over into the cycloadduct. Intermediates A and C would therefore hardly have enough time to isomerize to conformers B and D, respectively, by way of a rotation about the C—C single bond between the two C atoms that used to be connected by a configurationally stable C=C double bond in the starting ester. However, it seems unbelievable that not even as little as 0.003% of either of the potential intermediates would have 

Side Note 15.3. Isoxazolines as Synthetic Equivalents in Organic Chemistry 

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

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]...

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). 

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... 

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... 

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. 

The 1,3-dipolar cycloaddition of diazoalkanes to alkynes leads to pyrazoles, e.g. ... 

There are numerous other 1,3-dipoles of the S2une type, from azides ( —N3) to ozone (O3). Huisgen (1963 a, 1984, p. 5) lists 18 examples, which lead to an enormous variety of heterocyclic and other compounds. Previously, these compounds were either unknown or difficult to obtain. No wonder that a book of two volumes (1623 pages) was published on 1,3-dipolar cycloadditions by Padwa in 1984 This development is one of the most remarkable examples in organic chemistry that application of the principles of physical organic chemistry can lead to a complete and very diverse framework of synthetic methods. We agree with Padwa s statement that Huisgen s work in this area was monumental. We will discuss 1,3-dipolar cycloadditions of diazoalkanes in Sections 6.2-6.4. 

The rates of 1,3-dipolar cycloadditions of diazoalkanes to alkenes and alkynes have been determined electron-attracting substituents in the latter increase the rate, in accordance with frontier molecular orbital theory, which predicts that these reactions are controlled by the interaction of the highest occupied molecular orbital of the diazo-compound with the lowest unoccupied molecular orbital of the dipolarophile " the kinetics of the reactions of methyl diazoacetate or phenyl diazomethanesulphonate, on the other hand, give rise to U-shaped activity functions, which is also explained by the theory. Diazomethane or... 

Dipolar cycloadditions of diazoalkanes with alkenes lead to pyrazolines, which are easily transformed into cyclopropanes. 

Dipolar cycloaddition of diazoalkanes with alkenes and alkynes gives pyrazolines and pyrazoles, respectively (Scheme 5.9). 

A long-known route to pyrazoles is the 1,3-dipolar cycloaddition of diazoalkanes (e.g., as efficient catalyst-free version using a-diazoesters [438]) to aUcynes ... 

The classical synthetic method for homoquinones is based on the 1,3-dipolar cycloaddition of diazoalkanes to 1,4-quinones. This reaction consists of the addition of diazoalkanes to the quinonoid CC double... 

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