Decalin cycloaddition

Feringa-butenolide 114, in the presence of Dess-Martin periodinane reagent and 2,6-lutidine, gave the bis-ketone 115 which underwent intramolecular cycloaddition to afford endo-selectively the desired decalin-based lactone 116 (Equation 2.32) [114]. Double activation of butenolidic double bond strongly increases the reactivity of dienophile 115. 

An intramolecular cycloaddition reaction of 117 is the crucial step in the synthesis of the highly functionalized decalin [115] moiety of azadirachtin 119. 

The extensive study of Craig and coworkers [116] on the intramolecular Diels-Alder reactions of E- and Z-sulphonyl-substituted deca-, undeca- and dodecatrienes 120 (Figure 2.13) has opened a short route to trans- and cis-bridgehead hydrindanes and decalines and has given new insights into the role of dienophile substitution and geometry in determining the stereochemical outcome of these intramolecular cycloadditions. 

Decalin unit 121, an intermediate in the total synthesis of compactin, has been prepared by intramolecular cycloaddition reaction [117] of trienone-carboxylic acid 122 carried out under either thermal conditions or microwave irradiation. The desired cxo-adduct 123 was the major stereoisomer (Equation 2.34). Similar results were observed in the cycloadditions of the corresponding esters. 

Interestingly, the electron-transfer activation of cis- and trans-DBC cycloadditions with chloranil as a sensitizer leads to a mixture of cis- and trans-decalin adducts (equation 72). 

Starting from quinic acid, a highly substituted, cis-afi unsaturated nitrile oxide has been synthesized and used in a 1,3-dipolar cycloaddition, to afford a precursor of the cis -decalin system of branimycin (468). 

In an approach by Jung and Nishimura, the assembly of the dysidiolide decalin skeleton 54 was deemed possible via an intermolecular Diels-Alder reaction between cydohexene 52 and dienophile 53 [14]. Based on precedent established by Wulff et al. [15] [where Z = C(OCH3)=Cr(CO)5], the cycloaddition should give predominantly the exo isomer as shown (Scheme 19.12). However, all attempts to effect the cydoad-dition simply gave recovery of starting material. It was reasoned that steric hindrance was to blame. The steric hindrance assodated with the dienophile was decreased by replacing one of the methyl groups with another double bond in the... 

Intramolecular nitrile oxide-alkene cycloadditions also provide efficient access to six-membered rings such as cyclohexanes or decalins that are heavily adorned with functional groups and side chains. For example, this strategy was used to prepare racemic hemaldulcin (213), which is a 3,6-disubstituted cyclohexenone found in a Mexican plant that possesses a strong sweet taste. Starting from (2Z,6E)-famesal (209) (328) (Scheme 6.88), the aldehyde was treated with hydroxylamine... 

The intramolecular nitrile oxide-alkene cycloaddition has further been used for the construction of a tricyclic isoxazoline intermediate containing a decaline ring. 

Scott Denmark of the University of Illinois reports (J. Org. Chem. 68 8015,2003) a hetero intramolecular Diel-Alder reaction of a nitro alkene 5, followed by intramolecular dipolar cycloaddition of the resulting nitronate 6, to give the tricycle 7. Raney nickel reduction effected cleavage of the N-0 bonds and reductive amination of the liberated aldehyde, to give, after acetylation, the angularly substituted cis-decalin 8. 

Occidentalol (628), a eudesmane-type sesquiterpene isolated from the wood of Eastern white cedar, was synthesized from a as-fused decalin system (627) prepared by cycloaddition of the a-pyrone (625) with 4-methyl-3-cyclohexenone (626 Scheme 140) (72TL4651). Derivatives of 2-pyrone have also been employed in syntheses of colchicine (629 Scheme 141) (59AG637) and barrelene (630 Scheme 142) (69JA2330). 

Morrison reported that inms-decalin (181) is photochemically inert, but the cis isomer (182) undergoes a singlet-derived, intramolecular meta cycloaddition to give 183 (Scheme 54). Compound 183 efficiently photocycloeliminates to give a carbene-derived product 184 [238],... 

Also of interest are cyclohexenones with the tether attached at the 4-position, which have not been as widely applied as the 2- and 3-substituted cycloalkenones. Croft and Jeffries irradiated the dia-stereomeric enones (61) and obtained two cycloaddition products and two products from intramolecular hydrogen atom abstraction (equation 98). All the products contained a trans decalin, however. This re-... 

Thiazoles have a low reactivity in cycloaddition reactions due to their high aromatic character. However, it has been possible to achieve intramolecular Diels-Alder reactions in some cases. The reaction of the acetylenic thiazole (66) in decalin at 350 °C affords, after loss of acetonitrile, the thiophene derivative (67) in 75% yield (Equation (16)). The reaction is also applicable to other thiazoles although with some limitations <88T3327>. 

The 2-pyrone 116 (Scheme 33), containing the weakly electron-donating carbamate group at C3, has been reported to undergo cycloadditions with alkynes in refluxing decalin or tetralin, providing aniline derivatives 118 upon elimination of CO2 and aromatization... 

Alkenylenones have not been as widely utilized as the corresponding 2- and 3-alkenylenones. The photocycloaddition of various allenes attached to cyclohexenones and cvclopentenones at the 4-position has been reported and two examples are shown. Irradiation of the cyclopentenone 1 resulted in the formation of the straight adduct 2 and product 3 in a 1 1 ratio140. Compound 3 is formed by reaction across the 1,2-double bond of the allene function. Photocycloaddition of the cyclohexenone derivative 4141, as a 3 2 mixture of anti- and, vv -diastereomers at — 70 C, resulted in quantitative cycloaddition of the anti-diastereomer to yield the cis decalin system 5. The syn-diastereomer gave three minor photoproducts which were not characterized. 

A number of total syntheses of decalin polyketides have been reported, supporting the feasibility of biosynthetic cycloadditions. Actual involvement of PKS (lovastatin PKS and chlorothricin PKS) and PKS-NRPS (cheaoglobosin PKS-NRPS and equisetin PKS-NRPS) as Diels-Alderases is discussed in Section 8.08.4. Intramolecular Diels-Alder reaction could occur either during or after chain elongation of polyketide chain. 

The stereoselectivity predicted by the Alder rule is independent of the requirement for suprafacial-suprafacial cycloaddition because both the endo and exo TSs meet this requirement. There are many exceptions to the Alder rule and in most cases the preference for the endo isomer is relatively modest. For example, although cyclopentadiene reacts with methyl acrylate in decalin solution to give mainly the endo adduct (75%), the ratio is solvent sensitive and ranges up to 90% endo in methanol. When a methyl substituent is added to the dienophile (methyl methacrylate) the exo product predominates. ... 

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