Triazolinedione cycloaddition

Another series of publications from Ken s group compared kinetic isotope effects, computed for different possible transition structures for a variety of reactions, with the experimental values, either obtained from the literature or measured by Singleton s group at Texas A M. These comparisons established the most important features of the transition states for several classic organic reactions — Diels-Alder cycloadditions, Cope and Claisen rearrangements, peracid epoxidations, carbene and triazolinedione cycloadditions and, most recently, osmium tetroxide bis-hydroxylations. Due to Ken s research, the three-dimensional structures of many transition states have become nearly as well-understood as the structures of stable molecules. 

A selection of the many applications of cycloaddition with the triazolinedione 264 follows. 

Simple 2/7-chromenes produce [2+2] cycloaddition products upon reaction with triazolinediones such as phenyl-triazolinedione (PTAD) and methyl triazolinedione (MTAD) (Equation 11) <1995T13277>. 

From a purely synthetic viewpoint, triazolinedione adducts have served as substrates for gaining access to numerous target molecules such as prismane, semibullvalene, bridged semibullvalenes, elassovalene, caged compounds, and azoalkanes. Indeed, the title reagent can be used not only as a chiral source, but also as an azo donor. In the synthesis of 4,5-diazatwis-4-ene, for example, (-)- nfirst step involved cycloaddition to cyclooctatetraene dibromide with formation of a separable mixture of diastereoisomers. Eventual removal of the... 

Applications of (-)-enasymmetric synthesis in cycloaddition reactions have shown low levels of induction. In the examples studied, (-)-endo-bomyltriazolinedione reacted almost instantaneously with various dienes even at low temperature (<96°C) resulting in low asymmetric induction (<10%). The high reactivity of triazolinedione in [4 + 2] tt-cycloadditions due to its high dienophilicity minimized differentiation between the transition states and has to date impeded its use in asymmetric synthesis. 

Since their introducticm by Cookson et al. in 1962, 4-substituted l,2,4-triazoline-3,5-diones have been used extensively as dienophiles (equation 62). These dienophiles are highly reactive towards most 1,3-dienes and undergo cycloadditions under very mild conditions. In general, these Diels-Alder reactions are syn selective with respect to the diene, although with some (Z)-dienes this selectivity is lost. As noted above, it has been found that these cycloadditions are stepwise reactions in (Z)-dienes which cannot achieve an s-cis conformation. However, it is not clear if tdl cycloadditions of triazolinediones with 1,3-dienes proceed this way. 

Reaction of a cyclopropane with diazomethane or an azide generated cyclopropanes containing an azo function " a similar cycloaddition was reported for a nitri-limine. Cycloaddition of an ethandiylidene biscyclopropane and triazolinedione led to a hydrazine derivative Reactions of these types forming azo- or hydrazinocyclopro-panes are not subject of this review however, they could be of interest for aminocyclop-ropane synthesis by functional group interconversion (for the cycloaddition of cyclopropyl azide with a carbon-carbon double bond see Section II.E.3, equation 101). 

In the gas phase, 2 is a thermally very stable compound up to 850 °C. Pyrolysis at 880°C/10 Torr generates styrene (55-62%) and o-xylene (6%) along with small amounts of phenylacetylene, benzene, toluene and unidentified hydrocarbons. Cycloaddition reactions with dienophiles were among the first reactivity studies on 2 they were of course driven by the expectation to generate a cyclobutadiene structure by a twofold (4 + 2) cycloaddition. However, while 2 reacts readily with electron-deficient alkenes such as TCNE, A -phenyhnalermide, 4-phenyl-l,2,4-triazolinedione and diethyl azodicarboxylate to form 1 1 adducts 115, a second Diels-Alder reaction... 

That this difference in (4+2)-cycloaddition behavior most likely has steric origins—the methyl groups in 150 or the derived monoadduct preventing an ortho -addition of two equivalents of the dienophile—is supported by the observation that permethyl[6]radialene 95 is inert even towards the extremely reactive dienophile 4-phenyl-1,2,4-triazolinedione. ... 

Paquette s group has recently synthesized and evaluated chiral 4-sub-stituted triazolinediones in Diels-Alder cycloadditions.63 For example, endo-(-)-bomylamine has been converted to an azo dienophile, which has been used to resolve 1,2,3-trimethylcyclooctatetraene (Scheme 6-VII). In addition, triazolinediones derived from a-methylbenzylamine and dehydroabietylamine have been prepared and their reactions with achiral 1,3-dienes were investigated.636 Unfortunately, these dienophiles did not show good kinetic enantioselection, but they are useful for the type of resolution shown in Scheme 6-VII.630... 

Vinyl ethers spontaneously undergo reactions with triazolinediones to generate "zwitterionic or dipolar species which can either cyclize to yield the diazetidine or form alternating copol)rmers. Evidence for the intermediacy of the 1,4-dipole is based on the fact that it can be intercepted by a novel cycloaddition reaction with alkyl ketonesto yield the novel 1,3,4-tetra-hydrooxadiazine ring. 

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