Of A -capnellene

This reaction was used for an iterative cyclopentenone annelation in a synthesis of A " - -capnellene (2), formulated in part in Scheme (1). 

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. 

Other intramolecular aldol reactions have been reported. In the first total synthesis of A -capnellene-8/ ,10a-diol and A -capnellene-3y3,8/3,10a-triol Shibasaki et al. reported that excess la with Et3N effects the cyclization of intermediate 16 giving 17 in 42 % yield (Sch. 15), although a wide variety of different acidic and basic reagents meet with failure [46]. 

In the laboratory of K. Fukumoto, the stereoselective total synthesis of (+)-A -capnellene was carried out using an intramolecular Diels-Alder reaction to obtain a tricyclic 5-5-6 system. Since the target molecule was a triquinane, the six-membered ring had to be converted to a five-membered one, a transformation achieved by a Wolff rearrangement. The required a-diazo ketone was prepared via a deformylative diazo transfer reaction and was photolyzed in methanol. The ring-contracted methyl ester was isolated as a 3 1 mixture of separable isomers favoring the a-isomer. 

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... 

Asymmetric Heck reaction. The chiral product from an intramolecular process can he trapped. Thus, the method has been applied to a synthesis of (-)-A -capnellene and halenaquinone. Hypervalent alkenyliodonium salts can be used instead of triflates. 

The copper(I) catalysed photo-cycloaddition reactions of the dienes (160) have been studied. This process provides an efficient route to the (2+2) cycloadducts (160a) in the ratios and yields shown under the appropriate structures. These adducts are key components in an approach to the synthesis of A -capnellene. Copper triflate controlled photocycloadditions have also been used as a key step in the synthesis of some cyclopentanes. The reaction involves the cyclization of the dienes (161) under the copper(I) controlled conditions into the adducts (162) and this is followed by thermal reactions that bring about rearrangement and ring opening. 

Scheme 4.1 Synthesis of ( )-A -capnellene involving metathesis reactions 2—>4, 4— 5, and 6 7, facilitated by the Tebbe reagent Cp2Ti = CH2 see Section 2.2.1 (Stille...

The cascade process was initially explored with prochiral trienyl iodide 44 (Scheme 16.11) [36, 37]. Mizoroki-Heck cyclization of this precursor produced -ally(palladium species 45, which was trapped by acetate at the least-hindered terminus of the ry -aWyl system to provide CM-bicyclo[3.3.0]octadiene 46 in 60% yield, albeit with very low enantioselectivity (20% ee). Attempts to use silver salts as halide scavengers in this reaction led to the decomposition of 44, presumably resulting from the sensitivity of the cyclopentadienyl moiety. Mizoroki-Heck cyclization of prochiral vinyl triflate 47 with Pd(OAc)2, (S)-BINAP and tetrabutylammonium acetate was more productive, giving diquinane product 48 in excellent yield and 80% ee (Scheme 16.12). The corresponding allylic amine 49 was obtained in analogous fashion using benzylamine as the nucleophile [38]. Allylic acetate 48 was elaborated in seven steps to triquinane /3-ketoester 50, an intermediate in Shibasaki and coworkers [39] earlier total syntheses of ( )-A -capnellene-3/3,8/3,10a-triol (51) and )-A. -c3i me ene-5p, P,l0a,lA-i xdiO (52). 

Ohshima, T., Kagechika, K., Adachi, M. et al. (1996) Asymmetric Heck reaction-carbanion capture process. Catalytic asymmetric total synthesis of (—)-A -capnellene. J. Am. Chem. Soc., 118, 7108-16. 

The reaction, at room temperature (16 h), afforded the triquinane 37, a key intermediate in the synthesis of ( )A -capnellene, in 70% yield along with traces of the isomer having an internal double bond. Indeed, 37 could be converted to capnellene as a single isomer in three steps using conventional synthetic methods (50% overall yield). 

More recently, a cascade process that presumably consists of (i) oxidative addition of Pd to an alkenyl iodide, (ii) Pd-alkene 7r-complex formation, (iii) anti-attack by a carbon nucleophile, and (iv) reductive elimination has been devised. This cascade process has been used for the synthesis of ( )-A -capnellene (Scheme 22). 

Naturally Occurring Fused Cyclopentanoids.—Activity in this area continues to be intense. Little etal7 have used the rather low-yielding intramolecular 1,3-diyl trapping procedure in syntheses of A -capnellene (105) and the isomeric hirsutene (106), whereas in an alternative route to (105), sequential Nazarov and aldol cyclizations are used to build up the three ring system. Pyrolysis of the cage compound (107), derived from cyclopentadiene and 2,5-dimethylbenzo-quinone, leads to the hirsutene precursor (108) in high yield. The preparation of another potential precursor (110) to the hirsutanes by intramolecular [2 2]photoaddition of (109) has been detailed in full. ... 

Birch AM, Pattenden G. Biogenetically patterned synthesis of A -capnellene. Tetrahedron Lett. 1982 23 991-994. 

Curran, D.P. and Chen, M.-H. (1985) Radical-initiated polyolefinic cydizations in condensed cyclopentanoid synthesis total synthesis of ( )-A -capnellene. Tetrahedron Lett., 26, 4991-4494. 

Pattenden, G. and Teague, S.J. (1988) Total synthesis of ( )-A -capnellene-8p,10a-diol./. Chem. Soc. Perkin Trans. 1,1077-1083. 

Gambacorta, A., Fabrizi, G., and Bovicelli, P. (1992) Bicyclo[3.3.1] nonane approach to triquinanes formal synthesis of ( )-A capnellene and ( )-A capnellene-8P-10a-diol. Tetrahedron, 48, 4459-4464. 

Uyehara, T., Furuta, T., Akamatsu, M., Kato, T, and Yamamoto, Y, Construction of fused ring skeletons based on photochemical rearrangement of bicyclo [3.2.1 ]oct-6-en-2-ones and apphcation to a total synthesis of ( )- A -capnellene, /. Org. Chem., 54, 5411, 1989. 

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