1.3- Dipolar cycloaddition Tandem reactions involving

The addition of ZnBr2 to the tandem 1,3-azaprotio cyclotransfer-cycloaddition of a ketoxime with divinyl ketone results in rate enhancement and the exclusive formation of l-aza-7-oxabicyclo[3.2.1]octan-3-ones7 The 1,3-dipolar cycloaddition of 1-aza-l-cyclooctene 1-oxide with alkenes produces the corresponding isoxazolidines in high yields with a minimum of polymeric material. The cycloaddition of thiophene-2-carhaldehyde oxime with acetonitrile and methyl acrylate produces the 1,3-dipolar adduct, suhstituted isoxazolidines, and not the previously reported 4 - - 2-adducts. Density functional theory and semi-empirical methods have been used to investigate the 3 + 2-cycloaddition of azoxides with alkenes to produce 1,2,3-oxadiazolidines. The 3 -h 2-cycloaddition of a-nitrosostyrenes (62) with 1,3-diazabuta-1,3-dienes (63) and imines produces functionalized cyclic nitrones (64) regioselectively (Scheme 22). The first imequivocal 1,3-dipolar cycloaddition of sulfines involves the reaction of 2,2,4,4-tetramethyl-3-thioxocyclobutanone S-oxide with diaryl thioketones to produce... 

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). 

Triazole Derivatives. Triazole derivatives are known to possess tumor necrosis factor-a (TNF-a) production inhibitor activity. The synthesis of triazole derivatives can be achieved from alkynes or diynes by a tandem cascade reaction involving 1,3-dipolar cycloaddition, anionic cyclization and sigmatropic rearrangement on reaction with sodium azide. Some of the benzoyl triazole derivatives were considered to be potent local anaesthetics and are comparable with Lidocaine. The triazoles can also be prepared from benzoyl acetylenes,triazoloquina-zoline derivatives, 2-trifluoromethyl chromones, aliphatic alkynes, 2-nitroazobenzenes, ring opening of [ 1,2,4]triazolo [5,1-c] [2,4]benzothiazepin-10 (5//)-one, alkenyl esters and dendrimers. A number of these reactions are outlined in eqs 44 8. 

A tandem one-pot reaction of an aldehyde with a primary amine involving condensation and then cyelization (N-alkylation ), followed by intramolecular dipolar cycloaddition of the resulting nitrone or azomethine ylide, provides a synthesis of bridged tricyclic amines. 

Coldham et al. reported on a cascade reaction sequences involving condensation, cyclization, intramolecular dipolar cycloaddition for preparation of fused tricyclic heterocycles which can be converted in two steps to a 1,3-oxazine present in some yuzurimine-type Daphniphyllum alkaloids under some conditions [57], In another study, addition of hydroxylamine to substituted 4-chlorobutanals gives intermediate nitrones that imdergo tandem cyclization and then intramolecular dipolar cycloaddition to give the core... 

Muthusamy and co-workers have demonstrated [82] the reactions of the bicyclic ylide 57, generated from the diazocarbonyl compoimd 56, with symmetrical and unsymmetrical dipolarophiles. Thus, exposure of the cyclohexanone-substituted a-diazocarbonyl compound 56 to DMAD in the presence of Rh2(OAc)4 as the catalyst has furnished the cycloadduct 58 (Scheme 16). This cycloaddition was diastereoselective and, in the case of unsymmetrical dipolarophiles such as methyl methacrylate and propargyl bromide, they were regioselective and afforded oxygen heterocycles 59 and 60, respectively. The same research group has reported the 1,3-dipolar cycloaddition of the bicyclic carbonyl yUde 57 with other dipolarophiles, namely fulvenes [83]. In these tandem cycUzation-cycloaddition reactions involving fulvenes, four stereocenters and two new C-C bonds are formed in a single step. Symmetrical dipolarophiles such as macrocycHc olefins were also used for diastereoselective 1,3-dipolar cycloaddition reaction with 56 [84]. 

A range of indolo(triazolo)-l,4-diazepine derivatives 104 were obtained by a microwave-heated three-component reaction involving tandem N-alkylation of indole 101 with epichlorohydrin 102, ring-opening of the epoxide with azide 103, and intramolecular azide-alkyne 1,3-dipolar cycloaddition reactions (13BJO401). Fused triazolodiazepinones were obtained via azide-alkyne 1,3-dipolar cycloaddition followed by lactamization (13JHC430). 

A four-component reaction involving tandem indium chloride-catalyzed cyclocondensation of ammonium acetate 124, glyoxal derivatives 125,2-azidobenzaldehyde derivatives 126, and propargylamines 127 followed by intramolecular azide-alkyne 1,3-dipolar cycloaddition reactions afforded highly functionalized benzo-imidazo-triazolodiazepines 128 (130L4492). 

Sometimes, nitronates are involved in tandem [4+2]/[3+2] cycloaddition processes. That is, the first step consists on the formation of the nitronate (starting from a nitroalkene) and the second is the 1,3-dipolar cycloaddition between the nitronate and an electron-deficient alkene. This is the case of the next example. The reaction between nitroalkene 7 and 2,3-dimethyl-2-butene 8 in the presence of a Lewis acid and under the conditions indicated in Scheme 22.3 yields tricyclic adduct 9. 

The synthesis of tricyclic compound 120 was first reported by Tamura and co-workers using a tandem transesterification-cycloaddition reaction of nitrone methyl ester 118 and cyclohexen-3-ol (Scheme 16.17). This reaction was catalyzed by titanium tetrachloride to make nitrone cyclohexenyl ester 119. A subsequent 1,3-dipolar cycloaddition reaction proceeded presumably through a transition state involving the i-cis-like conformation of the ester C—O bond and the E configuration of the nitrone C=N bond (Scheme 16.17). 

Denmark advanced a strategy that involves tandem cycloaddition sequences with nitronates for the asymmetric synthesis of alkaloids [73, 74). A camphor-derived auxiliary permits the preparation of chiral enol ethers (cf. 68) as the reacting partners. A noteworthy example of the complex structures that could be generated by use of 68 is illustrated in Scheme 18.15. A hetero-Diels-Alder reaction between 68 and nitronate 67 generated 69 as a 96 4 mixture of endo/exo diastereomers. The adduct then participated in an intramolecular dipolar cycloaddition at elevated temperatures to yield cycloadduct 70 as a single diastereomer (90%). The tricyclic target 72 was obtained in 88 % yield after reductive removal of the chiral auxiliary and lactam formation [74]. 

---