Capnellene reaction

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]. 

The reaction of alkenyl iodides or triflates, alkenylstannanes, and CO affords divinyl ketones[397,398]. Thus the capnellene skeleton 538 has been synthesized by the carbonylation of the cyclopentenyl triflate 536 with the alkenyltin 537[392], The macrocyclic divinyl ketone 540 has been prepared in a moderate yield by the carbonylative cyclization of 539[399]. 

On the basis of the examples addressed thus far, it is clear that radical reactions can accomplish manifold transformations in organic synthesis. One of the outstanding achievements of synthetic radical chemistry is the development of synthetic strategies based on controlled, tandem radical cyclizations. The efficiency of such strategies is exemplified in the substantial and elegant synthetic work of D. P. Curran and his group.54 The remainder of this chapter will address the concise total syntheses of ( )-hirsutene [( )-1]55 and ( )-A9(12)-capnellene [( )-2]56 by the Curran group. 

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. 

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... 

The key steps in Mehta s synthesis of (+)-A9(12)-capnellene (408), also constitute a formal olefin metathesis reaction. 

Oxophilic phosphomum compound 47 forms from tributylphosphine (46) and the phenylselenide 45, and this then suffers nucleophilic attack by alcohol 18. The resulting free selenium nucleophile 48 displaces phosphine oxide 50 with the formation of phenylsele-nide 51. Phenylselenide 51 is oxidi/ed by hydrogen peroxide to phenylselenoxide 52, which at room temperature undergoes an elimination reaction to (-)-A9tl2)-capnellene (1). The mechanism is similar to that of the Cope elimination, proceeding via a cyclic transition state. 

The Tebbe reagent reacts with some alkenes. The tricyclo[5.3.0.0] ring 207 was obtained nearly quantitatively by domino alkene metathesis and carbonyl alkenation of the norbomene-type ester 205 with the Tebbe reagent. This interesting reaction to give the intermediate 206 can be explained by the kinetic preference of the Tebbe reagent for the strained double bond over the ester. Alkenation of the ester in 206 produces 207. Capnellene (208) has been synthesized by applying this reaction as a key reaction [65],... 

Three new chirality centers are formed with high enantio- and complete diastereoselectivity in the course of the reaction of the enol triflate 37 to the bicyclo [3.3.0]octane derivative 38 (Scheme 11) [15]. In this transformation, the intermediate 39, formed by oxidative addition, leads to the cationic palladium-7r-allyl complex 40, which is finally converted to the isolated product 38 by regio- and diastereoselective nucleophilic addition of an acetate anion. The bicyclic product 38 is of interest as a building block for the synthesis of capnellene sesquiterpenes. 

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

If this reaction is carried out as an intramolecular reaction, interesting ring systems are produced. This reaction was used to produce a precursor to capnellene and involves all the same reactions as used in the polymer synthesis (equation 14). 

The synthesis of capnellene discussed earlier is an interesting example in which (3) was used to generate a new titanium alkylidene which then underwent an intramolecular reaction with an ester carbonyl. The process effectively involved carbonyl alkylidenation by a substituted titanium alkylidene (equation 14). In this case steric factors apparently account for the desired reaction selectivity. ... 

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]. 

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... 

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. 

A linear triquinane synthesis is started from a bicyclo[6.3.0]precursor initiated by chemoselee-tive Lewis acid attack on the least hindered olefin. Reaction of precapnelladiene (10) to capnellene (11) can be carried out in refluxing benzene in the presence of boron trifluoride-diethyl ether complex22 giving a yield of greater than 50%. 

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