Double cycloadditions

Pentacylic cage compounds 202 were synthesized through a double cycloaddition reaction to methylenecyclopropene 199, which involves an intermol-ecular 1,3-dipolar cycloaddition of 198 on the endo double bond to give 200 followed by an intramolecular Diels-Alder reaction between a benzylidenecyclo-propane moiety and an ene function (Table 19) [49],... 

A double cycloaddition approach has also been used to construct cycloadducts which are converted into homochiral polypropanoates <1996TL4149, 2001HCA431>. Thus, 2,2 -ethylidenebis[3,5-dimethylfuran] undergoes a double cycloaddition with diethyl (2it,5i4)-4-oxohepta-2,5-dienoate under high pressure to give the adduct in high yield as the only product (Equation 102). 

Ab initio and density functional theory (DFT) calculations were used to explain the peri- and regioselectivity of the double cycloaddition reaction of arylnitrile oxide with norcaradiene tautomer 7 of 3,5,7-trimethyl-5//(l,2)diazepine 6 forming cycloadduct 8 <2002JST(580)183> (Scheme 1). 

Tsuge and co-workers - building on work by Bailey and Blomquist [5] - have already made extensive use of the preparative potential of these so-called diene transmissive Diels-Alder additions (DTDA additions) [8]. Clearly, the dienophile does not have to be identical in the two stages of the reaction, which increases the preparative potential of these double cycloadditions considerably. The adducts of type 22 can be further processed in various ways, for example by dehydrogenation to give 1,2,6,7-tetrasubstituted naphthalene derivatives as will be discussed below. Consecutive reactions of this type with their excellent atom economy are of considerable interest particularly in view of the current efforts to increase the efficiency of organic transformations. 

Addition reactions of 2-substituted N- methylpyrroles with C- acetyl-TV- phenylnitrilimine gave double cycloaddition products, spiro-cycloadducts and noncyclic bis-adducts (78JHC293). 

The reaction of homochiral allylsilanes with a-enones and a-enals is very valuable for the asymmetric synthesis of multisubstituted cyclopentanes (Equation (40)).161,162 The [3 + 2]-cycloaddition of allylsilanes is applicable to />-quinones163 and />-quinoneimines.164 3-Butyn-2-one undergoes a double cycloaddition with an excess amount of allyltriisopropylsilane to give a bicyclo[3.3.0]octane in good yield (Equation (41)).165... 

Metal-catalyzed decomposition of diazomethane in the presence of 1,2,3,4,5,6-hexamethyl-bicyclo[2.2.0]hexa-2,5-diene (11, hexamethyl Dewar benzene) has been shown to give the simple or double cycloaddition products with exo configuration. When the reaction was carried out in the absence of a metal catalyst, the products of C-H insertion to allylic C-H bonds were also observed, in addition to cycloaddition to the double bond to an extent of 25%. A C-C insertion reaction at the unusually long central bond of hexamethyl Dewar benzene was not detected. The reaction conditions were designed to generate methylene in the singlet state, and the observed products were those that would be expected for the reaction of singlet methylene with hexamethyl Dewar benzene. 

Double cycloaddition. In the presence of an excess of dmad, the increased 1,3-dipolar reactivity of 13, or rather 14, leads to a second cycloaddi-... 

The product distribution depends on the isocyanide used. Only with aromatic (R = o-tolyl or 2,6-xylyl), and not with aliphatic isocyanides (R = Bu , Bu or benzyl) are isonitrile insertion products 24 formed. Aryl isocyanide insertion is obviously very fast since the competing formation of 23 from CO insertion is not observed complexes 22 are only minor products. With aliphatic isocyanides, the thpp complexes 22, from double cycloaddition of dmad cf. Section 3.1.1), are the major products (70 to >95% of the product mixture) and indicate a strongly increased 1,3-dipolar reactivity, i.e. the intermolecular second cycloaddition is preferred to the intramolecular CO insertion. Compared with the ruthenium compound 17, the thpp in 22 is strongly bound to the metal and can only be decomplexed oxidatively with cerium(iv), or under 80 bar of CO. 

The reaction of 25a-c with dmad proceeds in a manner completely analogous to the reaction of 21, i.e. giving thpp complexes by double cycloaddition in case of the aliphatic isonitriles (b, c), and isonitrile insertion with the aromatic... 

Addition of DMAD to the pyrrolo[3,4-c]pyrazole (236) gave (237) in quantitative yield. This reaction proceeded via a vinyldiazo intermediate <89JOC59l2>. Double cycloaddition of the A-ylide (238) with activated acetylenes gave (239) in 26% yield <87JCS(Pl)253l>. 

By using a 1,2,3,4-tetrahalobenzene in which metal-halogen exchange occurs preferentially at the 1 and 4 halogens, one has a synthetic equivalent of 1,3-benzadiyne 433 . For example, the highly strained permethylphenanthrene 454 can be synthesized in this way by a double cycloaddition to 452. Initial exchange occurs primarily at the iodine atoms of 452. 

The first approach, a one-step intermolecular double cycloaddition (137 — 136), required synthesis of the 1,2-di(benzocyclobutenyl) ethane 142, which proceeded in a straightforward manner (Scheme 20). Thus, Knoevenagel reaction of... 

On the other hand, reactions of 4-heteroaryl-2-methyldienamines 304 with tetrazines 1 furnished 4-heteroaryl-pyridazines 307 and dihydropyridazines 308 in 38-92% yields. Presumably, these two products are formed by initial double cycloaddition of the tetrazine 1 to both G=C bonds to give the intermediate 306, which disproportionates into 307 and 308 (Scheme 73) <1999TL6313>. 

Nan ya and co-workers " reexamined the double cycloaddition of munchnone 42 with two equivalents of several maleimides 198 to give cycloadducts 199 and 200 (Fig. 4.69). Whereas A-phenylmaleimide 198a gives only the exo, endo adduct... 

Highly regioselective double cycloaddition to 2,5-dichlorobenzoquinone and subsequent elimination has been used in the manufacturing of highly substituted anthraquinone derivative shown in Scheme 16.33 [35],... 

A double cycloaddition is encountered in the reaction of o-diazo oxides and dimethyl-or diphenylketene. The first step is an addition of the ketene to the diazo oxide to give 325,... 

A double cycloaddition is postulated for the formation of the functionalized bicyclo[4.2.0]octanes 141 (Scheme 5.49). The former is a Diels-Alder reaction starting from a Danishefsky s diene 139 and acrylates 140, whereas the latter is a [2 -I- 2] cycloaddition, both steps being catalyzed by EtAlCl2 [132]. The method was extended to the total synthesis of the cytotoxic natural compound paesslerin A. 

Moreover, Tsuge and coworkers [83] revealed a double cycloaddition of pyridinium M-methylide 328 to methylenecyclopropene 315 to provide the cage... 

Warrener et al. have shown that cyclobutene epoxides 126 undergo C-C ring opening into cyclic carbOTiyl ylides 127 that can be quenched by alkenes in 1,3-dipolar cycloaddititMis, generating 7-oxanorbomane derivatives 128 (Scheme 19) [159, 160], The method has been applied to construct molecular devices such as 131 by double cycloadditions of norbomene derivatives 129 to the bis-epoxide 130. 

Nakamura E, Isobe H, Tokuyama H, Sawamura M. Regio- and diastereo-controlled double cycloaddition to [60]fullerene one-step synthesis of Cs and C2 chiral organofullerenes with new tris-annulating reagent. Chem. Commun. 1996 1747-1748. 

A promising one-step route via rhodium-catalyzed double [2-I-2-1-2] cycloaddition was described for the synthesis of tetra-ort/70-substituted axially chiral diaryls from the diyne and tetrayne substrates produced from available alkynes [66]. Enantioselective syntheses of both C2 symmetric and asymmetric tetra-ort/ o-substituted axially chiral diaryls 2.72 and 2.75 through the rhodium-catalyzed [2-I-2-I-2] double cycloaddition of either 2.70 or 2.73 to the diyne 2.71 or tetrayne 2.74, respectively, gave products with ee 99% (Scheme 2.26) [66]. 

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