Cedrane synthesis

Sequential radical cyclizations are also featured in an efficient and clever synthesis of the cedrane framework 83 (see Scheme 15).30 Compound 81, the product of a regioselective Diels-Alder reaction between isoprene (79) and nitroethylene (80), participates in a nitroaldol reaction (Henry reaction) with 5-methyl-4-hexenal in the presence of a basic resin to give 82. Because the nitro group in... 

An alternative synthesis of pyrimidine boronic acids, which avoids lithiation chemistry altogether, has been developed <2001SL266>. Thus, reaction of 2,4-dimethoxy-5-iodopyrimidine 352 with cedrane-8,9-diolborane 351 using catalytic amounts of Pd(PPh3)4 and Cul gave the intermediate boronate 353 which could be converted to the free boronic acid 354 in 83% yield by transesterification with diethanolamine, followed by treatment with acid (Scheme 3) <2001SL266>. 

Few synthetically useful examples of the oxidation of ethers by oxygen or ozone have been publish-ed.7 96 Q0 In 1978, Ourisson and coworkers reported that ozonization of the natural product cedrane oxide (43) on silica gel at -78 °C led to the formation of the corresponding lactone (44) in 30% yield (equation 32).A small amount of the tertiary alcohol (45) was also produced. Later, in the course of a chiral total synthesis of compactin, Hirama examined the ozonolysis of the alkene (46 equation 33). ° Under carefully controlled conditions, selective ozonolysis of the double bond could be achieved in 88% yield. However, when excess ozone was employed, significant amounts of the benzoate (47) were obtained, even at -78 C. In subsequent studies, benzyl ethers of primary and secondary alcohols,and carbohydrates were oxidized to the corresponding benzoates in excellent yields. Surprisingly, no further synthetic rqrplications of this reaction have been reported. 

A number of model esters related to lac resin have been prepared. These esters have the basic cedrane skeleton (149) or the C-2 epimeric structure. In an approach to the synthesis of cedrene (152), the intramolecular photocycloaddition of the dienone (150) was carried out at low temperature. A major tricyclic compound (151) was obtained and its structure was verified by X-ray analysis of its anisylidene derivative. Further work is required to bring about the rearrangement of a derivative of (151) to give cedrene. Further details on the hydroxylation (with O3) and chlorination (with PhICl2) of cedrol, patchoulol, and their derivatives have been presented. The results of this study are in keeping with those obtained previously. 

A fruitful application of this strategy was carried out in the field of natural product synthesis. Easy access to imidazole alkaloids isoanantine and anantine was in fact possible following the model reaction (equation (17)) [53]. More recently the same researchers accomplished the synthesis of an intermediate in the route to ( ) oxoparabenzolactone following the method reported in equation (18) [54]. In the synthesis of natural terpenes, a-acoradiene was quantitatively converted to cedrane [48]. 

Based on the fascinating biogenetic relationships that exist among monocyclic, spiro and tricyclic sesquiterpenes, several unusually simples routes have been devised to the cedrane skeleton. " One such synthesis of Q -cedrene is outlined below, and proceeds from nerolidol, presumably along lines of the proposed biogenesis. ... 

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