Of cedrene

Review Problem 17 Design a synthesis for TM 206, an intermediate in Crandall and Lewton s biogenetically patterned synthesis of cedrene ( J. Amer. Chem. Soc.. 1969, 91, 2127). 

Another synthesis of cedrene and of cedrol was achieved via the following sequence (Ref. 2) ... 

Although the constitution of cedrene is not understood, Semmler and Hoffmann consider that the following complexes are present in the various bodies described —... 

Semmler and Risse have studied the oxidation of cedrene by means of ozone. They obtained the keto-acid, Cj Hj Oj, which on further oxidation either by means of bromine or nitric acid yields a dicarboxylic acid. 

C,4H2204, melting at 182 5. The formation of this cedrene-dicarboxylic acid serves for the detection of cedrene in essential oils. It is sufficient if the fraction to be examined be oxidised by permanganate or ozone, and the acid obtained (boiling-point at 10 mm. = 200° to 220° C.) be then oxidised further, either by an alkaline solution of bromine or by nitric acid. Even very small proportions of cedrene have definitely led to the obtaining of this acid melting at 182 5° C. 

Semmler and Mayer have isolated from the oil of cedar wood an alcohol, pseudocedrol. There also exists in the oil a sesquiterpene alcohol, cedrol. The latter, on dehydration yields cedrene, which is probably identical with, or very closely allied to, natural cedrene, whilst pseudocedrol yields a mixture, when heated in a sealed tube, of cedrene and dihydrocedrene. Dihydrocedrene is a colourless oil having the following characters —... 

No crystalline halogen derivatives of cedrene have been prepared, only liquid compounds being obtained when the sesquiterpene is treated by the usual processes. 

Making elegant use of the intramolecular arene-olefin meta-cycloaddition reaction, Wender and Howbert have achieved a total synthesis of ( + )-cedrene (575) Irradiation of 569 led to an approximately equal mixture of 570 and 571 which... 

I shall end the program with one complete synthesis that of cedrene, the essential oil of cedar wood. The synthesis has many steps and requires some reactions you haven t met, but I thought you would like to see the carbonyl group in action. Here it is ... 

Similar diastereofacial selectivity was found in the photoaddition of 267 affording a mixture of 268 and 269 in 4 1 ratio respectively. This reaction was used as the key step reaction in the synthesis of ( )-cedrene 269121 (Scheme 58). 

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. 

The syndesis of cedrene served to establish a firm foundation for the implementation of the meta cycloaddition in complex molecule synthesis and allowed also for a comparison of the effectiveness of an arene-alkene based strategy with the many impressive approaches to this well-known target. On the other hand, the next application of the meta cycloaddition was directed at isocomene (90 Scheme 10), a relatively new structural motif but one which has been found with increasing frequency in new natural... 

Further pathways that may be followed include hydride transfer, leading to the possibility of more remote functionalization of the carbon skeleton, and carbon migration, leading to a rearranged skeleton. This is more common when there is a quaternary center next to the carbenium carbon, or in polycyclic systems, as observed in the acetylation of cedrene. ... 

Treatment of either cedrol or cedrene with methanol in the presence of acid, results in the formation of cedryl methyl ether (6.116), which possesses a strong woody-amber odour. The intermediate from either starting material is the carbocation (6.120). Treatment of cedrene with... 

Friedel-Crafts Acylation of Cedrene. Let us now look in a little more detail at the Friedel-Crafts acylation of cedrene. This reaction can be carried out using acetic acid or acetic anhydride with an acid catalyst such as formic acid, phosphoric acid or sulfuric acid. The species which attacks the double bond of cedrene is the protonated acid or anhydride molecule. When sulfuric acid is used as a catalyst with acetic anhydride as the reagent, it is thought that the sulfuric acid first sulfonates the acetic anhydride to give sulfoacetic anhydride (6.122) as the acylating species. This results in a faster reaction as the sulfoacetate anion (6.126) is a... 

Anomalous Behaviour of Cedrene under Friedel-Crafts Conditions. Sesquiterpene chemistry is always full of surprises. For example, during some investigations into alternatives for the existing acetylcedrene processes, an attempt to use titanic chloride in place of... 

Selinene is another sesquiterpene found in woods. Its behaviour in the Vilsmeier-Haack-Arnold reaction is, like that of the acylation of cedrene using titanic chloride as a catalyst, another interesting and surprising piece of sesquiterpenoid carbocation chemistry. 

A phenol need not be used directly, as long as a phenoxide anion can be formed easily. Spirocyclization of the bis(methanesulfonate) 754 to 755 is a useful example where the requisite phenolic anion is generated in situP Spirocyclization was used by Corey as well as by Crandall and Lawton to construct the spirocyclic portion of cedrene, 758. In independent syntheses, phenolic ester 756 was cyclized to 757 in good yield. Corey used the methyl ester T obtained a 53 47 mixture of (Z/E) isomers of 757. Corey also found... 

Use C. find wide use in the perfume industry rectification of the oils furnishes starting materials for further substances used in perfumes, e. g., cedrol methyl ether and cedry 1 acetate from cedrol, acetyIcedrene from the mixture of cedrene/thujopsene, and cedrene epoxide from a-cedrene. 

According to Semmler cedrenol stands in the same relation towards cedrene as the two primary alcohols of the santalol series towards the sesquiterpenes, Cig 4, the santalanes and as myrtenol and the ginger-grass alcohol stand towards pinene and limonene. The primary CHjOH group in the cedrenol molecule occupies the same position which is occupied by the GH, group in cedrene and in solid cedrol. Hence the relation of cedrene towards cedrol and cedrenol is as follows... 

Eousset has studied the oxidation products of cedrene, from which he obtained the ketone cedrone, CijHj O, by means of chromic acid. On reduction this yields an alcohol, isocedrol, isomeric with cedrol. 

Others. Cedarwood oil Virginia is used in microscopy as a clearing agent and, thickened together with resins, as an immersion oil. It can also serve as source of cedrene, a starting material for fragrance chemicals. 

Corey, E. J. Balanson, R. D. Simple synthesis of ( )-cedrene and ( )-cedrol using a synchronous double annulation process Tetrahedron Lett. 1973, 14, 3153-3156. 

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