Oxygen diene syntheses with

Only a few cyclic dialkyl peroxides have been prepared by reaction with hydrogen peroxide. The large class formed by the endoperoxides, most of which are prepared by diene synthesis with oxygen, is discussed in Section IV. 

Oxygenated dienes are exceptional substrates for vinylcarbenoids [78]. In order to avoid side-products derived from zwitterionic intermediates, nonpolar solvents are typically employed. A short synthesis of nezukone 57 highhghts the utiHty of the [3-1-4] cycloaddition for the synthesis of tropones (Scheme 14.4). The cycloaddition between the oxygenated butadiene 55 and 52 generates the cycloheptadiene 56 in 67% yield [78]. Treatment of 56 with Meli followed by acid-induced dehydration completes a very short synthesis of nezukone 57. 

The autoxidation of 1,3-dienes is generally of minor importance for the synthesis of cyclic peroxides, the principal route to which is the photooxidation of 1,3-dienes. For this process, a sensitizer must be added in the case of low molecular weight 1,3-dienes and the 1,3-dienes of the terpene and steroid series. No sensitizer is required in the photooxidation of condensed aromatic hydrocarbons. These reactions may be regarded as diene syntheses with oxygen as the dienophile.165 A... 

Diels-Alder cycloadditions of carbonyl compounds with aldehydes and ketones provide a powerful method for synthesis of 5,6-dihydropyrans, which are useful synthons for a variety of purposes. This methodology was slow to develop since early work indicated that simple carbonyl compounds react poorly with most alkyl and aryl substituted 1,3-dienes. However, with the understanding that [4 + 2] cycloadditions are facilitated by Lewis acid catalysts and high pressure, along with the recent availability of highly reactive oxygenated dienes, this chemistry has been increasingly exploited in total synthesis. 

Carboxyl-substituted N-sulfonylimines have also been used in [4 + 2] cycloadditions, and some examples are shown in Scheme 2-11. - Imine 14 adds regioselectively to isoprene to give only one adduct, but diene 15 surprisingly afforder a 3 1 mixture of adducts. The major exo adduct produced from siloxydiene 16 was recently used in total synthesis of the piperidine alkaloids isoprosopinine B and deoxyprosopinine. The highly oxygenated diene 17 was found to react with both acyclic N-sulfonylimine 18 and cyclic imine 19 to afford cycloadducts. 

In Rainier s synthesis of the hemibrevetoxin B ring system,diene 169, which is obviously related to Danishefsky s diene, reacted with O-benzyl 4-hydroxybenzaldehyde, in the presence of zinc chloride, to give 170 in 92% yield. Pyrones and pyrans are particularly useful for the preparation of acyclic precursors to macrocyclic antibiotics. The stereochemistry of the highly oxygenated acyclic fragment can be controlled by exploiting the selectivity inherent in the cyclic pyran (sec. 6.5). 478 xhe disconnection for this reaction is... 

Extension of the [3+4] annulations to more highly oxygenated dienes results in a very effective synthesis of tropones and tro-polones. For example, decomposition of the vinyldiazomethane 4 in the presence of 1-methoxy-l-trimethylsiloxy-1,3-butadiene (46) results in the formation of the cycloheptadiene 47 in 87% yield (Scheme 18). Mild hydrolysis of 47 with citric acid followed by DDQ oxidation results in a very short synthesis of the tropone 48 in 92% yield. The [3+4] annulation with 1-methoxy-l-trimethylsiloxybutadiene is applicable to a range of vinyldiazomethanes, as shown in Table 8. The major limitation is that because of the extremely electron-rich character of the diene, the formation of side products derived from zwit-terionic intermediates dominate over the [3+4] annulation. In general, the side reactions are eliminated by carrying out the reactions in a nonpolar solvent. 

The hydrindan 23b was later converted by the same group into 26 (Scheme 7), which is a key intermediate in the synthesis of ( )-oppositol and (-)-prepinnaterpene.f The conversion involved oxidation of the diene moiety with singlet oxygen and is notable for the clean epimerization of the ring junction to give the fratis-conflguration (from 25 to 26), which demonstrates that both cis- and unctions can be obtained in the AHR products. 

Stereoselective synthesis of 1-oxygenated dienes, starting from propargylic esters, has been reported with gold catalysts [168]. In this case, a 1,2-H shift on cyclic intermediate 196 allows the formation of a vinyl gold intermediate 197, which, upon protodemetalation, furnishes the (1 ,3 ) diene 198 (Scheme 80). 

The same mixture of H and I was obtained starting with either of the geometrically isomeric radical precursors E or F. A possible explanation is based on the assumption of a common radical conformer G, stabilized in the geometry shown by electron delocalization involving the radicaloid p-orbital, the p-peroxy oxygen and Jt of the diene unit. The structure of the compounds H and I were determined by H NMR spectra and the conversion of H to diol J, a known intermediate for the synthesis of prostaglandins. 

A great advantage of catalyst 24b compared with other chiral Lewis acids is that it tolerates the presence of ester, amine, and thioether functionalities. Dienes substituted at the 1-position by alkyl, aryl, oxygen, nitrogen, or sulfur all participate effectively in the present asymmetric Diels-Alder reaction, giving adducts in over 90% ee. The reaction of l-acetoxy-3-methylbutadiene and acryloyloxazolidinone catalyzed by copper reagent 24b, affords the cycloadduct in 98% ee. The first total synthesis of ewt-J -tetrahydrocannabinol was achieved using the functionalized cycloadduct obtained [23, 33e] (Scheme 1.39). 

For the construction of oxygen-functionalized Diels-Alder products, Narasaka and coworkers employed the 3-borylpropenoic acid derivative in place of 3-(3-acet-oxypropenoyl)oxazolidinone, which is a poor dienophile in the chiral titanium-catalyzed reaction (Scheme 1.55, Table 1.24). 3-(3-Borylpropenoyl)oxazolidinones react smoothly with acyclic dienes to give the cycloadducts in high optical purity [43]. The boryl group was converted to an hydroxyl group stereospecifically by oxidation, and the alcohol obtained was used as the key intermediate in a total synthesis of (-i-)-paniculide A [44] (Scheme 1.56). 

The Diels-Alder reaction of nitroalkenes with Danishefsky s dienes is applied to synthesis of truncated carbocyclic analogues of a potent neuraminidase inhibitor 4-guanidino-NemAc en fsee Scheme 8.5. Carbocyclic analogs are found to retain interesting levels of antiviral activity comparable to those shovm by their oxygen-containing compounds in Scheme 8.5. 

In a synthesis of gibberellic acid, a diene and quinone, both with oxygen-substituted side chains, gave the initial intermediate. Later in the synthesis, an intramolecular D-A reaction was used to construct the A-ring. 

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