As/<9 -Capnellene

The Nazarov cyclization has been featured in a variety of synthetic endeavors involving both natural and unnatural products. In the area of polyquinane natural products ( )-hirsutene (88), ( )-mod-hephene (89), ( )-silphinene (90), ( )-A 2)-capnellene (91) and ( )-cedrene, have all been prepared (Scheme 37). The synthesis of (91) is noteworthy in the iterative use of the silicon-directed Nazarov cyclization. TIk divinyl ketones were constructed by the carbonylation-coupling of enol triflates (92) and (95) with the -silylvinylstannane (Scheme 38). llie diquinane (94), obtained from Nazarov cyclization of (93), was transformed into enol triflate (95) which was coupled with the -silylvinylstaimane as before. Silicon-directed Nazarov cyclization of (96) was highly diastereoselective to provide the cis,anti,cis isomer of (16). The synthesis was completed by routine manipulations. 

Although it probably did not involve a Heck reaction per se, Balme and co-workers employed an interesting tandem reaction in their construction of A 2) capnellene (147) (Scheme 6-26) [54J. Presumably vinyl iodide 144 undergoes initial oxidative addition with the palladium(O) catalyst to furnish a cr-alkenylpalladium(n) intermediate that is complexed to the pendant alkene. Intramolecular addition of the soft malonate nucleophile to this complex, from the opposite face, followed by reductive elimination, then provides tricycle... 

In a typical example of aliphatic cyclizations, already discussed in Section 5.2, the enamine 675 is alkylated by silylated methyl 4-chloroacetoacetate 747 a [2] to give, via 760 and subsequent ehmination of pyrrolidine, the unsaturated bicycHc /9-ke-toester 761 in, as yet, only 30-40% yield [1]. Analogously, the bicycHc system 1408 with an additional 6-keto group is silylated to 1409 and cyclized via 1410, in an overall yield of 42%, to the tricyclic capnellene intermediate 1411 [3] (Scheme 9.1). An alternative synthesis of bicyclic compounds Hke 761 is given elsewhere [3 a]. 

This reaction was used for an iterative cyclopentenone annelation in a synthesis of A9(,2)-capnellene (2), formulated in part in Scheme (I). 

In the cyclopentenyl series the relative stereoselection is variable. With a simple methyl substituent vicinal to the newly forming bond the selectivity is poor. This may be remedied with bulkier silyl groups (Scheme 19) but in unacceptable yields. In the synthesis of ( )-A -capnellene, Stille reports the formation of a single c/f, anrj,cjf-triquinane (16) in the final SDNC. By contrast in an approach to hirsutene, the SDNC produced triquinane (17) as a 2.7 1 mixture favoring the desired d.r,anr/,c i5 isomer. 

The linearly fused tricyclopentanoids have attracted widespread interest. Their biological activity and interesting molecular architecture have made them the focus of many synthetic endeavours [1]. Those discussed in the first portion of this chapter include hirsutene (1), A<9,2>-capnellene (2), coriolin (3), and hypnophilin (4). 

The silyl enol ethers 209 and 212 are considered to be sources of carbanions. and their transmetallation with Pd(OAc)2 forms the Pd enolate 210. or o.w-tt-allylpalladium, which undergoes the intramolecular alkene insertion and. 1-elimination to give 3-methylcyclopentenone (211) and a bicyclic system 213[199], Five- and six-membered rings can be prepared by this reaction[200]. Use of benzoquinone makes the reaction catalytic. The reaction has been used for syntheses of skeletons of natural products, such as the phyllocladine intermediate 214[201], capnellene[202], the stemodin intermediate 215[203] and hir-sutene [204]. 

Curran s synthesis of ( )-A9(l2)-capnellene [( )-2] is detailed in Schemes 30 and 31. This synthesis commences with the preparation of racemic bicyclic vinyl lactone 147 from ( )-norbomenone [( )-145] by a well-known route.61 Thus, Baeyer-Villiger oxidation of (+)-145 provides unsaturated bicyclic lactone 146, a compound that can be converted to the isomeric fused bicyclic lactone 147 by acid-catalyzed rearrangement. Reaction of 147 with methylmagne-sium bromide/CuBr SMe2 in THF at -20 °C takes the desired course and affords unsaturated carboxylic acid 148 in nearly quantitative yield. Iodolactonization of 148 to 149, followed by base-induced elimination, then provides the methyl-substituted bicyclic vinyl lactone 150 as a single regioisomer in 66% overall yield from 147. 

The capnellene (1) of marine origin and derivative capnellenols such as 2 belong to the family of sesquiterpenes. Similar terpenes with a tricyclic [6.3.0.01undeeane skeleton are also found in plants, including such substances as hirsutene (3) and corioline (4). 3... 

Endocyclic vinylcyclopropanes yield bicyclo[3.2.0]heptenes 4 and 5 under irradiation with either 200- or 450- medium-pressure Hanovia lamps, or in a Rayonet photoreactor (254-nm lamps). This methodology was used in the syntheses of the terpenes grandisol and capnellene. ... 

However, the same transformation when applied to substrates habing a substituent at C4, offered products in moderate to good diastereoselectivity, thus leading to chiral bicy-clo[3.2.0]hept-2-enes, important building blocks in organic synthesis. Their utility was demonstrated by the formal synthesis of both the enantiomers of A -capnellene.f J... 

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