Cycloadditions under

Miscellaneous Reactions. Some hydantoin derivatives can serve as precursors of carbonium—immonium electrophiles (57). 5-Alkoxyhydantoins are useful precursors of dienophiles (17), which undergo Diels-Alder cycloadditions under thermal conditions or in the presence of acid catalysis (58). The pyridine ring of Streptonigrine has been constmcted on the basis of this reaction (59). 

The photochemical addition of simple olefins to a,j -unsaturated ketones is a reaction of great current interest. The steroidal A -20-ketone system is especially prone to cycloaddition under mild conditions. Sunder-Plassmann et irradiated 3j5-acetoxypregna-5,16-dien-20-one (67) in the presence... 

Carbene complexes containing either the dienophile or the diene functionality bonded directly to the carbene carbon undergo intramolecular [4+2] cycloadditions under mild conditions [108] (Scheme 60). 

The o-quinodimethanes are very reactive, unstable dienes, which are usually prepared in situ. The cycloaddition under high pressure of the dibromo-o-quinodimethane 91, generated in situ from a,a,a, a -tetrabromo-o-xylene. 

Keywords cycloaddition under thermal conditions, diastereofacial selectivities, Lewis acids... 

Triazoles have been obtained via microwave-assisted [3-i-2] cycloaddition, under solvent-free conditions [54], starting from organic azides and acetylenic amides at 55 °C for 30 min (Scheme 23). The complete conversion of the reagents into AT-substituted-1,2,3-triazoles 69 was achieved without decomposition and side products. A control reaction carried out at the same temperature in an oil bath did not give the cycHc products, not even after 24 h of reaction time. 

Shao reported the microwave-assisted hetero-Diels-Alder cycloaddition reaction of a series of acetylenic pyrimidines to introduce a fused lactone/lactam ring, with no degradation of either reactants or products typical for the harsh thermal conditions (150-190°C, 15-144h) [131]. In contrast to the results reported when conventional heating was applied, the Diels-Alder cycloaddition under microwave irradiation gave a high yield of the desired fused lactones or lactams [132]. This reaction provided a practical and general method for the preparation of fused bicyclic pyridines 205 (Scheme 74). 

A regio- and stereospecific INOC reaction of unsymmetrical silaketals 114, synthesized in one pot from unsaturated alcohols, nitro ethanol, and dichloro-silanes, via the nitrile oxide 115 to isoxazolines 116 has been described (Scheme 14) [37a]. The intermolecular version of the cycloaddition, under similar conditions, proceeds with poor regio and stereoselectivity. 

An efficient synthesis of rigid tricyclic (5 5 5) nitrogen heterocycles 64 has been achieved via sequential and tandem Ugi/intramolecular Diels-Alder (IMDA) cycloaddition of pyrrole derivatives <2004JOC1207> and the trienes 477 were prepared by the acylaton of amines 475 with the anhydride 476. The amines 475 were in turn prepared starting from pyrrole-2-carbaldehyde. The triene 477 on heating in toluene at 80 °C for 15 h underwent the IMDA to afford the tricyclic compound 64 as a single diastereomer in quantitative yield. The sterically bulky N-substitutent on the triene 477 promoted cycloaddition under milder condition at 65 °C in toluene to provide the tricyclic compound 64 in quantitative yield (Scheme 108). 

While doubly activated dienophiles gave moderate to good yields under thermal conditions (Table 11), mono activated alkenes such as cyclohexenone (123) failed to react at temperatures up to 150 °C but underwent cycloaddition under Lewis-acid catalysis even if with poor yields (Table 12, entries 1-3) [32],... 

Previous work [111] by our group has demonstrated that RTIL-catalyzed 1,3-dipolar cycloaddition under the action of microwave irradiation leads to dramatically shorter reaction times with better yields of isolated products. We have recently investigated the reactivity of the formyl group covalently grafted on the ionic liquid phase 75 in the Knoevenagel reaction with malonic derivatives 76 [112], as shown in Scheme 8.76. 

In the nineteen-nineties, numerous examples of 1,3-dipolar cycloadditions under microwave heating were reported with a wide variety of dipoles. In many cases the product yields and/or reaction times were improved and the method was used to prepare valuable compounds that could not be obtained by classical heating and, in some instances, the regioselectivity of the reaction was modified. Most of these processes were performed in the absence of solvent. 

In the following section the main 1,3-dipolar cycloadditions under microwaves will be reviewed according to the nature of the dipole. 

This methodology has also been used by Bose, who described the synthesis of the thienamycin side chain [119], the first step of which was a [2+2] cycloaddition under microwave irradiation. Likewise, Khajavi described the reaction of trichloroacetic anhydride with imines [120] with classical heating the reaction requires the use of Fe2(CO)9 as a catalyst, whereas under microwave irradiation a catalyst is not required. 

The enone system itself is usually part of a five- or six membered ring, although acyclic a,(3-unsaturated ketones and enols of P-diketones are also found to undergo cycloadditions under certain conditions. For seven- and higher membered rings the primary photochemical event is Z—E isomerization around the C—C double bond, the E-isomer then eventually undergoing further thermal reactions. 

Reactions of Cjq with metal carbene complexes also yield the [6,6] methano-fullerenes [392]. These adducts are probably not formed via a carbene addition, but via a formal [2-1-2] cycloaddition under formation of a metalla cyclobutane intermediate. The Fischer carbene complex [mefhyl(methoxymethylene)]pentacarbonyl chromium can be utilized to prepare l,2-mefhyl(methoxymethano)-fullerene in 20% yield [392]. A tungsten carbene complex was primarily used to initiate the formation of a polyacetylene polymer, but it was discovered that addition of to the complex-polymer-mixture improves the polymerization and dramatically increases the catalytic activity of the carbene complex [393]. can be integrated into the polymer via carbene addition. 

The generation of a nitrile oxide bearing a carbamoyl group (i.e., 16) was effected by treating 4-nitro-3-isoxazoline-5-one (15) with a mixture of acetonitrile and water (Scheme 6.5). Although the mechanism of this reaction is not clear, the method allows for the formation of a functionalized nitrile oxide (16) and subsequent cycloaddition under mild conditions (91). 

When the reaction is carried out on l-acetyl-3-piperidinoindole, the tricyclic intermediate corresponding to (255) can be isolated (78AHC(23)263, 80JOC462). Enhanced yields of benz-azepines are reported by carrying out the cycloadditions under high pressures (80H(14)1959, 81H(16)1367). 

The dehydrohydantoins (lOOa-c) are active dienophiles and undergo [4 + 2] cycloadditions under mild conditions even with dienes of modest activity. The reactivity of the dehydrohydantoin depends markedly on the substituent in the 5 position with (100c) (100b). The 5-phenyl compound... 

The bicyclo[4.2.1]nonatriene 323 was prepared by the [6+2] cycloaddition of internal alkyne with the complex 322 under irradiation [79]. Ligand exchange of 323 with toluene liberated 324. The complex 325 underwent the [6+2] cycloaddition with two moles of terminal alkyne to give the tetracyclic compound 327 via 326. The [6+2] cycloaddition of the complex 322 and 1,7-octadiyne (328) afforded 329 as a primary product, which was converted further to 330 in 56% yield by further intramolecular [6+2] cycloaddition [80]. The tropone complex 331 underwent intramolecular [6+2] cycloaddition under irradiation to give the strained tricyclic compound 332 in moderate yield [81]. 

Cycloaddition under thermolytic conditions is another route to tricyclic /3-lactams. The 1,3-dipolar cycloaddition of oxazolidinone 98 with /V-phenylmaleimide to give 100 has been described (see Section 2.04.6.3). In a sealed tube at 100 °C the oxazolidinone 98 reacts with a cyclopentenone derivative to give the tricyclic isomers 378 and 379 in the yield ratio of 4 1 (Equation 52) <1999JHC1365>. 

Phosphinine and its derivatives are clearly aromatic however, they are considerably more reactive than benzene. The most significant influence on the reactivity of these molecules is the presence of the lone pair on phosphorus, and two significant reactions are its complexation with a variety of metals, and nucleophilic attack to form (ultimately) A5-phosphorins. The 71-system can undergo [4+2] cycloadditions, under milder conditions than benzene. Electrophilic substitution reactions on carbon are considered to be impossible <2001CRV1229>. 

Triplex catalysis.1 1,3-Cyclohexadiene does not undergo cycloadditions under usual conditions although it is known to dimerize on irradiation in the presence of a sensitizer. Actually, 1,3-cyclohexadiene can undergo both [2 + 2]- and [4 + 2]cycloaddition with a silyl enol ether such as 1-trimethylsiloxy-l-phenylethyl-ene (1). Similar results obtain with trimethylsilylketene acetal. These sensitized... 

Interestingly, tricarbonyl compounds such as 2-85, but not 2-89, can also undergo a cycloaddition under irradiation to give a different type of dihydropyran. 

In contrast to the hydrazones mentioned above, a,/ -unsaturated N -sulfonyl imines react as electron-deficient diene component in aza Diels-Alder reactions. In addition to several investigations dealing with their intermolecular cycloadditions under thermal and under high pressure conditions [231-234], Boger s... 

In response to a more fundamental question, a qualitative understanding of the origins of the treble diastereoselectivity exhibited in each cycloaddition has been developed. Arguments based on discussions in the literature have been combined with synthetic observations made in our own laboratories to assess the factors which control the reactivities and selectivities of exocyclic r-m-butadiene units, and endocyclic bisdienophilic units incorporating the (2.2. l]bicycloheptane skeleton. The syn/endo-H stereochemistry generated across each newly-formed cyclohexene ring in the cycloadditions between bisdiene and bisdienophilic building blocks is, we believe, a consequence of transition state considerations, and therefore a result of kinetic control. In spite of the sometimes tacitly assumed reversibility of the Diels-Alder reaction, evidence is provided in this review that confirms here at least the unidirectional nature of the cycloadditions under discussion. 

Dinica, R.M., Druta, I.I., and Rettinari, C. 2000. The synthesis of substituted 7,7 -bis-indolizines via 1,3-dipolar cycloaddition under microwave irradiation. Synlett, 1013-15. 

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