Ozonolysis cyclohexadienes

Problem 10.22 In the Birch reduction benzene is reduced with an active metal (Na or Li) in alcohol and liquid NHj(-33 °C) to a cyclohexadiene that gives only OCHCH CHO on ozonolysis. What is the reduction product ... 

Since the diene gives only a single product on ozonolysis, it must be symmetrical. The reduction product is 1,4-cyclohexadiene. 

Ozonolysis of cyclic olefins in the presence of carbonyl compounds gives the corresponding cross-ozonides.1329 In the ozonation of 1,2,4,5-tetramethyl-1,4-cyclohexadiene, oxidative dehydrogenation (formation of 1,2,4,5-tetramethylben-zene) was found to compete with oxidative cleavage because of steric hindrance.1330 Secondary ozonides (the 76 1,2,4-trioxolanes) are formed in high yields in the gas-phase, low-temperature ozonation of terminal and disubstituted alkenes.1331... 

Ozonolysis of the double bond in 1,4-cyclohexadiene 943 followed by reductive work-up and dehydration provides the dihydropyran-4-one 944, an intermediate during a formal synthesis of leucascandrolide (Equation 369) <2002CC2066>. 

Epoxidation of l,2,4,5-tetramethyl-l,4-cyclohexadiene with MCPBA provided the epoxide 302 in 65% yield. Subsequent ozonolysis of 302 gave a mixture containing 84% of the 1,2-dioxocin 303 and 16% of the epoxy ketone 304, from which 303 was isolated in 38% yield (Scheme 62) <2001EJ01899>. 

Problem 9,20 Predict the ozonolysis products of (a) cydohexene (b) 1-methyl-cyclopentene (c) 3-nieth>lcycloi entenc (d) 1,3-cyclohexadiene (e) 1,4-cyclohexa-diene. 

Ozonolysis as used below is the oxidation process involving addition of ozone to an alkene to form an ozonide intermediate which eventually leads to the final product. Beyond the initial reaction of ozone to form ozonides and other subsequent intermediates, it is important to recall that the reaction can be carried out under reductive and oxidative conditions. In a general sense, early use of ozonolysis in the oxidation of dienes and polyenes was as an aid for structural determination wherein partial oxidation was avoided. In further work both oxidative and reductive conditions have been applied . The use of such methods will be reviewed elsewhere in this book. Based on this analytical use it was often assumed that partial ozonolysis could only be carried out in conjugated dienes such as 1,3-cyclohexadiene, where the formation of the first ozonide inhibited reaction at the second double bond. Indeed, much of the more recent work in the ozonolysis of dienes has been on conjugated dienes such as 2,3-di-r-butyl-l,3-butadiene, 2,3-diphenyl-l,3-butadiene, cyclopentadiene and others. Polyethylene could be used as a support to allow ozonolysis for substrates that ordinarily failed, such as 2,3,4,5-tetramethyl-2,4-hexadiene, and allowed in addition isolation of the ozonide. Oxidation of nonconjugated substrates, such as 1,4-cyclohexadiene and 1,5,9-cyclododecatriene, gave only low yields of unsaturated dicarboxylic acids. In a recent specific example... 

In the ozonolysis of 1,3-dienes, one double bond often can be cleaved selectively, and in 1,3-cyclodienes, the regioselectivity in fragmentation of the primary ozonide depends upon the size of the rings (eq 13). Eq 13 shows that as the ring size contracts from cyclooctadiene to cyclohexadiene, the a,/3-unsaturated ester becomes favored over the enal. 

Finally, the interesting study of Pinelo et al on the ozonolysis of 1,3- and 1,4-cyclohexadiene shall be mentioned here. The obtained experimental and theoretical results demonstrated that these reactions predominantly do not follow the long-accepted Criegee mechanism. Instead, the reaction of O3 with 1,4-cyclohexadiene led to the essentially... 

Lithiated allyl sulfide 256-Li reacted with m-xylylene dibromide 257 to afford the bis-sulfide 258. A double Mislow-Evans rearrangement of 258 and subsequent reductive trapping of the sulfenate ester provided the symmetric trans-diol 255. Monoprotection, Sharpless asymmetric epoxidation, and reductive ring-opening of the epoxide gave 1,3-diol 259 in 97% ee. After several functionalizations, the arene was subjected to Birch reduction to provide 1,4-cyclohexadiene 254. Ozonolysis of the diene, followed by reductive workup and treatment of the resulting 1,3-diketone with acid furnished pyra-... 

The proposed synthetic route to TM 2.8 starts with anisole, which on methy-lation and Birch reduction affords a derivative of non-conjugated cyclohexadiene TM 2.8g. The importance and mechanism of this reaction are discussed in Sect.5.4. Chemoselective hydrogenation of one C=C bond is possible since the double bond in enol ether C=C-OMe is less reactive. TM 2.8f affords ester-aldehyde TM 2. 8e on ozonolysis (Scheme 2.20). 

How can you distinguish between 1,3-cyclohexadiene and 1,4-cyclohexadiene based on their ozonolysis products ... 

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