4- phenyl-1,2,4-triazolin-3,5-diene, Diels-Alder

In order to smdy the effect of perturbation arising from spiro-conjugation on the chemical reactivities, in particular the facial selectivities, sterically unbiased dienes (96 and 97) based on fluorenes in spiro geometry have been synthesized [165]. These dienes react as Diels-Alder dienes with several dienophiles (maleic anhydride (MA), A-phenylmaleimide (PMI), A-phenyl-l,3,5-triazoUne-2,4-dione (PTD) and iV-methyl-l,3,5-triazoline-2,4-dione (MTD)). 

The syntheses have been reported of la,3/3-dihydroxy-4,4-dimethylcholesta-5,7-diene (269) and its 3a-epimer, along with the ergostane analogues/ As reported in the preliminary account, 4,4-dimethylcholesta-5,7-dien-3-one underwent the ene reaction with 4-phenyl-1,2,4-triazoline-3,5-dione to give (270) rather than the normal Diels-Alder adduct.Treatment of (270) with acid gave the trienone (271). Treatment of cholecalciferyl tosylate with aq. KHCO3-... 

Phenyl-l,2,4-triazoline-3,5-dione acts as a dienophile by in situ reaction with butadiene, cyclopentadiene, cycloheptatriene, and bicyclohepta-diene (62TL615). Thus, it is possible to compare the reactivity of the cis-azo dienophile (110) with trans-azo dienophiles, such as ethyl azodicar-boxylate, which has been observed to undergo alternate modes of reaction when used with less reactive or hindered dienes. Treatment of (110) with several dienes resulted in exclusively Diels-Alder addition. The results are summarized in Table III. 

In general, reaction of (110) with a wide variety of dienes was quite satisfactory (67JOC330). Only the most unreactive dienes such as hexachl-orocyclopentadiene and hexachlorobutadiene failed to react under the conditions employed. The chief limitation of this dienophile is that the mixture cannot be heated to force reaction without the decomposition of (110). Another important observation was the strong, almost complete preference for undergoing the Diels-Alder-type addition even when other reactions are possible. This may be attributed to the two favorable factors of cis configuration and electron deficiency that are exhibited by 4-phenyl-1,2,4-triazoline-3,5-dione. 

There have been only a few reports of reactions of this type including cycloaddition of dienes 157 with the powerful dienophile 4-phenyl-l,2,4-triazoline-3,5-dione <1996J(P1)2297> and stereoselective cycloaddition of the chiral nitrone 158 with a variety of dipolarophiles <2000JOC7000>. A rare example of intramolecular hetero-Diels-Alder reaction involving a 4-methylene-l,3-oxathiolan-5-one 3 -oxide is provided by the cycloaddition reaction of 159 to give 160 (Equation 42) <1998EJ02733>. 

In common with other azodicarboxylic acid derivatives, the uses of 4-phenyl-l,2,4-triazoline-3,5-dione are many. It undergoes a Diels-Alder reaction with most dienes and is, in fact, the most reactive dienophile so far reported.As with the formation of all Diels-Alder adducts the reaction is reversible, and in the case of the adduct with 3-j3-acetoxy-17-cyano-5,14,16-androstatriene, the reverse reaction can be made to proceed under especially mild conditions. An instance has also been reported of the dione photochemically catalyzing other retro Diels-Alder reactions. Along with the proven use of azodicarboxylic ester, the dione should be potentially important in the preparation of strained ring compounds. 

Cycloadditions of dienophiles with homotetraenes are also known. 1,2-Homohep-tafulvene (6-methylenebicyclo[5.1.0]octa-2,4-diene, 20) reacted with 4-phenyl-1,2,4-triazoline-3,5-dione to afford both an [8 + 2] cycloadduct 21 and a Diels-Alder product 22. 

Diels-Alder dienes Benzene, see Dicyanoacetylene. Cyclooctatetraene, see 4-Phenyl-l,2,4-triazoline-3,5-dione. Cyclopentadiene ketals. cis-7,8-Dichlorobicyclo[4.2.0]octadiene-2,4, see cis-3,4-Dichlorocyclobutene. 5,5-Dimethoxy-l,2,3,4-tetrachlorocyclopentadiene. Hexa-chlorocyclopentadiene. Methyl tra .rl2,4-pentadienoate. A 4 l6-Steroid dienes, see 4-Phenyl-l,2,4-triazoline-3,5-dione. Tetrachlorocyclopentadienone ethylene ketal ... 

Formation of Diels-Alder adducts between cyclohexa-1,3-dienes and 4-phenyl-l,2,4-triazoline-3,5-dione (Kobal et al. 1973) — This reaction is noted later as exemplification of the use of X-ray analysis and the absolute configuration of the dihydrodiols ... 

Ergosta-5,7,22,24(28)-tetraen-3jS-ol has been synthesised from ergosterol by ozonolysis to the 22-aldehyde and construction of the appropriate side-chain using a Wittig reaction. During these reactions, the 5,7-diene system was protected as the Diels-Alder adduct (546) with 4-phenyl-l,2,4-triazolin-3,5-dione, from which the homoannular diene could be regenerated in 99 % yield by reduction with lithium aluminium hydride. 

Other Addition Reactions.—A review on the applications of retro-Diels-Alder reactions has appeared. Reformation of the steroidal 5,7-dienes from the 4-phenyl-l,2,4-triazoline-3,5-dione adducts was achieved by heating with K2CO3 in DMSO or DME. This provides a very useful alternative to the previously reported L1A1H4 cleavage. A cation-radical mechanism was proposed... 

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