0-Santalene synthesis

Further studies on the biosynthesis of ovalicin (57) have demonstrated the use of deuterium magnetic resonance in biosynthetic studies. Compounds (59)—(62), structurally related to (-)-a-santalene (58), have been isolated from the essential oil of Lavandula ojficinalis and L. hybrida " An alternative synthesis of a-santalol... 

Suggest a synthesis of /8-santalene from the following ketone. (Do not worry about stereochemistry.)... 

Two new syntheses of /3-santalene (106) have been reported. In the first one, the starting material (105) was obtained from the Diels-Alder reaction between cyclopentadiene and methyl buta-2,3-dienoate followed by hydrogenation (Scheme 16). The second synthesis (Scheme 17) starts from camphene and... 

Allenic ester (334), nevertheless, displayed a sufficiently high dienophilicity towards cyclopentadiene to give, in the presence of TiCl2(OPr )2, exo-methylenenorbomene (335) in high yield and stereochemical purity (Scheme 82). The Diels-Alder process (334) - (335) served as the key step for a synthesis of enantiomerically pure (-)-3-santalene (337). The conversion of (335) into the natural product involved notably intermediate (336) which, owing to the attached auxiliary, could be efficiently purified by crystallization. 

Aral, Y, Yamamoto, M., and Koizumi, T., Enantioselective synthesis of the functionalized bicy-clo[2.2.1]heptane derivatives, key intermediates for the chiral synthesis of santalenes and santalols, Chem. Lett., 1225, 1986. 

Ni boride (obtained from sodium borohydride reduction of Ni acetate in ethanol) exhibits sensitivity to substitution on the double bond, and to strained double bonds , and hence is useful for selective half-hydrogenation of dienes. Ni boride selectively hydrogenates the strained double bond of norbonene and dicyclopentadiene. Thus, a synthesis of 13-santalene involves the selective saturation of the endocyclic double bond of 7 over Ni boride, to afford 8 in 98% yield ... 

The synthesis of cr-santalene from a,a-dimethylallyl bromide via 7r-allyl nickel complex is an elegant application. 

As part of a synthesis of santalene sesquiterpenoids, Barrett and McKenna (1971) treated cyclopentadiene (PI5.1) with the allenic acid (P15.2). This gave a mixture of two isomeric acids, (PI 5.3) and (P15.4). One of these, (PI 5.3) rearranged to the lactone (PI 5.5) on treatment with formic acid. The other remained unchanged. What are the structures of (PI5.3) and (PI5.4) and what are the mechanisms of the reactions (Figure PI 5). 

Reduction of norbornane-like precursors to natural products is also predictable. Reduction of the ketone unit in 330, in Money s synthesis of 3-santalene for example, gave the exo-alcohol 331 via attack from the less hindered endo face. Conversely, removal of the steric encumbrance at C7 (as in 332) gave attack via the exo face to give 333 (in about a 4 1 ratio favoring the endo alcohol shown). 4... 

The complete details of the synthesis of racemic dihydro-) -santalol (66) have been published. A new three-step synthesis of j8-santalene (71) has been... 

A number of cycloaddition reactions involving allene derivatives as dienophiles have been recorded. Allene itself reacts only with electron-deficient dienes but allene carboxylic acid or esters, in which a double bond is activated by conjugation with the carboxylic group, react readily with cyclopentadiene to give 1 1 adducts in excellent yield. For example, the allene 12 gave, with very high yield and selectivity, the cycloadduct 13, used in a synthesis of (-)-P-santalene (3.19). An allene equivalent is vinyl triphenylphosphonium bromide, which is reported to react with a number of dienes to form cyclic phosphonium salts. These can be converted into methylene compounds by the usual Wittig reaction procedure (3.20). 

Independently, Koizumi et al. also reported [160] the use of nonracemic 3-p-tolylsulfinylacrylates as dienophiles in highly diastereoselective Diels-Alder reactions. The functionalized bicyclo[2.2.1]heptane derivatives such as (186), obtained by asymmetric Diels-Alder cycloaddition of ethyl p-tolylsulfinylmethylenepropionate with cyclopentadiene, have been used as intermediates for the synthesis of bicyclic sesquiterpenes such as (+)-epi-P-santalene (187) [161,162] (Scheme 5.61). 

In solution in polar solvents the complexes couple with primary and secondary alkyl, aryl, vinyl and allyl bromides and iodides at or below room temperature. This was exploited by Corey as early as 1956 in his classic synthesis of a-santalene. Coupling via the Grignard reagent gave low yields. 

The synthesis of (+ )-sesquifenchene (450) and of ( )-epi-P-santalene (451) from the common intermediate (449), derived from endo-dicyclopentadiene, has been detailed. Conversion of (449) into the precursor of (450) makes use of the skeletal rearrangement that occurs during solvolysis of active 2-norbornyl esters. In a synthesis of (-H )-hinesol (452) and 10-epi-(-l-)-hinesol, interesting use has been made of a fragmentation reaction.The tosyl derivative (453), which was obtained in several steps from ( —)-P-pinene, was converted into the spiro[4,5]decane (455) on treatment with sodium hydride in DMSO the essential stereoelectronic changes are summarized in the intermediate (454). 

The reductive desulphurization of a cyclic sulphonic ester plays a primary role in a stereospecific synthesis of /3-santalene (Scheme 164). 

S)-5-Hydroxymethyl-2(5H)-furanone (8), derived from D-ribono-lactone, was used as an intermediate in a synthesis of the 6a-carbocycline analogue (9), with a Pauson-Khand reaction being used to build up the ring system from enyne (10) (Scheme 4). When alcohol (8) underwent Diels-Alder reaction with cyclopentadiene, either the (2S, 3R)-isomer (11) or its enantiomer could be produced by appropriate manipulation of the initial adduct face-selective Lewis-acid-catalysed Diels-Alder reactions of a,iS-unsaturated esters derived from D-mannitol could be used to produce the (R,R)-isomer (12) or its enantiomer.This chemistry was extended to give syntheses of (+)-0-santalene (13) and its enantiomer from (8) the starting material was prepared as described in Vol. 20 p.260, but a number of other papers dealing with routes to this intermediate are mentioned in the next section. 

The oxa-di-TT-methane rearrangement of /3,y-unsaturated ketones has been studied extensively, but has rarely been applied to synthesis. However, a recent application involved the formation of the tricyclic ketone (145) from the enone (144) as a key step in the synthesis of a-santalene (146) (Scheme 44). ... 

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