Dictamnol

The metal-catalyzed [5 + 2]-cycloaddition of tethered VCPs and 7r-systems has been applied to the total syntheses of (-l-)-dictamnol,52 (+)-aphanomol l,53 and tremulenolide A.54 The tricyclic core of cyathane diterpenes such as (-l-)-allocyathin B25S and the tricyclic carbon skeleton of polyhydroazulenes such as dolatriol56 were also synthesized... 

Wender et al. have demonstrated the power of the rhodium-catalyzed [5 + 2]-cycload-dition reaction discovered in their laboratories by synthesizing (+)-dictamnol (148) [33], Allenylvinylcyclopropane 145 was treated with rhodium biscarbonyl chloride dimer or rhodium tris(triphenylphosphine) chloride (Scheme 19.27). Both catalysts provided the cycloadduct 146 in 70-76% yield and high diastereoselectivity (8-9 1). The diaster-eoselectivity was attributed to the C8 hydroxyl group assuming a position on the less sterically encumbered exo face of the transition-state structure 147. 

Dicobalt octacarbonyl, in Pauson—Khand reaction homogeneous catalysis, 11, 340 metal-coupled promoters, 11, 339 non-oxidative promoter-assisted, 11, 338 oxidative promoter-assisted, 11, 337 physical promoters, 11, 339 solid-supported promoters, 11, 339 Dicobalt triple-decker sandwiches, preparation, 3, 14 (+)-Dictamnol, via [5+2]-cycloadditions, 10, 613-614 Dicyclohexylborane, for alkene hydroboration, 9, 150... 

The rhodium-cataiyzed intramoiecuiar [5+2] cycioaddition of an allene and vinylcyclopropane was the key step in the asymmetric total synthesis of the trinorguaiane sesquiterpene (+)-dictamnol by P.A. Wender and co-workers.The cyclization precursor allene-cyclopropane was assembled starting from commercially available cyclopropane-carbaldehyde. Using the HWE oiefination, the Weinreb s amide moiety was installed and subsequently reacted with a primary alkyllithium that was generated via lithium-halogen exchange. 

Finally, Sm -induced reduction of strained alkyl halides has also resulted in cleavage of carbon-carbon bonds [102], The method has been utilized as the key step in the synthesis of dictamnol (Eq. 92). Further development of the method has led to an approach to the aromadendrane carbon skeleton [103] by a radical frag-mentation/3-exo cyclization process (Eq. 93). 

The aglycone of 5 possess a trinorguaiane type skeleton. A related compound, dictamnol, with the same trinorguaiane type skeleton was previously reported from D. dasycarpus [9]. 

Dictamnol was also isolated during our investigation of the dichloromethane extract of the root bark of the plant [7],... 

Given the previously discussed examples of the [S-(-2] cycloaddition, one can imagine a variety of approaches to the synthesis of molecules like dictamnol. One which has found success is given in Scheme 8. The cycloaddition precursor is prepared in three steps fi om commercially available cyclopropanecarboxaldehyde. Cycloaddition of alcohol 68 proceeds in 69% yield to provide cycloadduct 70. The yield of the cycloaddition is improved to 80% by protecting the alcohol as a TBS ether (69), although the combined yield for cycloaddition and deprotection is 70%. With two additional steps from 70, dictanuiol (71a) was prepared in 10% overall yield, marking the first application of the metal-catalyzed [5+2] cycloaddition in natural product synthesis. 

Cycloaddition reactions of cyclopropanes via cleavage of the C—C bond have been apphed to the synthesis of a wide variety of natural products, particularly terpenoids. For example, (-H)-dictamnol [5], (-H)-aphanamol I [6], (-H)-tremulenolide A [7], and (-l-)-lirondosin A [8] were synthesized through a [5-h2] cycloaddition reaction of vinylcyclopropanes with C—C unsaturated bonds. ( )-Hirsutene [9], ( )-pentalenene [10], ( )-asterisca-3(15),6-diene [10], ( )-hirsutic acid [11], and (-l-)-asteriscanohde [12] were synthesized via rhodium(l)-catalyzed [5-H2-H1] cycloaddition of vinylcyclopropanes with alkenes and carbon monoxide. Total syntheses of ( )-a-agarofuran [13], and ( )-pyrovellerolactone [14] were also achieved through cycloaddition reactions of cyclopropane derivatives. For these syntheses, reference to the papers should be made directly. 

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