As/<9 -Capnellene synthesis

Oppolzer and coworkers extensively utilized such intramolecular magnesium-ene reaction in the synthesis of complex natural products. For example, A -capnellene has been synthesized by using this intramolecular allylmagnesiations iteratively (Scheme... 

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]. 

The transformation has been employed extensively in the preparation of precursors to a number of natural products [note Eqs. (26)-(32)], including, guaiazulene (163). dihy-drojasmone (165), rosaprostol (170), and convergent synthesis of (-)-valeranone (174), hirsutene (177), and A - -capnellene (182) [41]. The key cathodic cyclization step is illustrated for each natural product. 

The original Shapiro reaction involves the preparation of unfiinctionalized alkenes from ketone tosyl-hydrazones by quenching of the in situ generated alkenyllithium reagents with water. Recent applications of this reaction in natural product synthesis include the synthesis of 9(0)-methanoprostacyclin (Scheme 12), the in vitro conversion of humulene to A ( -capnellene (Scheme 13), the synthesis of die basic skeleton of isoadsirene (equation S2) ° and the total synthesis of the eudesmanolides rothin A and rothin B (equation 53). ... 

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... 

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