Cuparenic acid

Enzell C, Erdtman H 1958 The chemistry of natural order Cupressales. XXL Cuparene and cuparenic acid, two sesquiterpenic compounds with a new carbon skeleton. Tetrahedron 4 361-368... 

Cucurbitacin A, T50 Cucurbitine, A30 Cularine, K5 Culmorin, T28 Cuparene, T12 Cuparenic acid, T12 Cuparenol, T12 a-cuparenone, T12 Cupreine, K8 C-Curarine III, A37 ... 

Dipolar cycloaddition. Arylthiomethyl chlorides (1) in the presence of a Lewis acid can undergo a [4 + 2]cycloaddition to a tetrasubstituted alkene. They can be prepared by reaction of thiophenol with BrCH2Cl in the presence of DBU in CH,CN. C2H5A1C12 is preferred over A1C1, SnCl4, or TiCl4 as the Lewis acid. This reaction provides a short synthesis of cuparene (2). 

It has been suggested" that the formation of the keto-aldehyde (137) in relatively high yield from the sensitized photo-oxidation of thujopsene (138) can best be explained in terms of a dioxetan intermediate (139), similar examples of which have recently been found in singlet oxygen addition to electron-rich double bonds. An extensive analysis of the products of acid-catalysed rearrangement of thujopsene (138) has been carried out." Under different acid conditions ten products have been isolated and identified these include the known compounds, chami-grene (140), cuparene (141), and widdrol (142 R = H) together with the previously unknown compounds (142 R = Et) and (143)—(148). The authors have put forward a mechanistic scheme to explain the formation of all these compounds based on interconversions of cyclopropylcarbinyl and homoallyl cations. 

With cations ranked according to their relative stability, we then assume that given a choice, the more stable cation will be formed in a reaction because it is lower in energy. The addition of HCl to methylenecyclobutane (100) illustrates this point, where the final product is 1-chloro-l-methylcyclobutane (103), used by Fitjer in a synthesis of cuparene. 29 7 0 n bond reacts as a base, donating a pair of electrons to the acid (H+ = HCl). When the new C—H bond is formed, a carbocation is generated at the other carbon of the jt bond, leading to... 

From (-)-cuparene (322), ve metabolites (328-332) all of which contained cyclopentanediols or hydroxycyclopentanones were obtained. An aryl methyl group was also oxidized to give primary alcohol, which was further oxidized to afford carboxylic acids (329-331) (Hashimoto et al., 2001a) (Figure 20.96). 

From (a)-cuparene, six metabolites (333-338) were obtained. These are structurally very similar to those found in the metabolites of (-)-cuparene, except for the presence of an acetonide (336), but they are not identical. All metabolites possess benzoic acid moiety. 

The benzene ring of ( )-cuparene78bas been assembled using RCM as akey step (Scheme 17.15) [34]. In this work, the advanced 1,4-dicarbonyl intermediate 80 was converted into diene 81, which then underwent an RCM reaction to afford cyclohexene 82. This compound was then aromatized under acidic conditions to afford ( )-cuparene 78 without any major problems, yielding the natural product as a racemate in very few steps. 

In the last few years, several groups have developed enantioselective domino reactions catalysed by combinations of organocatalysts with palladium complexes. As an example, Murkheqee and List have reported a domino synthesis of p-all earbon quaternary amines on the basis of a highly enantioseleetive a-allqrlation of a-branched aldehydes, involving an achiral palladium catalyst and a chiral phosphoric acid. Under the catalysis of phosphoric acid, a secondary allylamine reacted with an a-branehed aldehyde to form an enammonium phosphate salt, which upon reaction with palladium catalyst afforded a cationic 7t-allyl palladium complex (Scheme 7.2). This intermediate resulted in the formation of an a-allylated iminium ion, whieh eould be reduced to the corresponding final chiral amine in high yield and exeellent enantioselectivity of 97% ee. The synthetic utility of this transformation was also demonstrated hy a formal synthesis of (+)-cuparene. 

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