Trienyl triflate

Polyene Heck-type cyclization,3 Overman s group has reported bicyclization of trienyl triflates to spirobicyclic systems in the presence of Pd(OAc)2/P(C6H5)3 (1 4) and 2 equiv. of N(C2H5)3. Under these conditions 1 cyclizes to 2 in 72% yield. This cyclization is particularly facile when catalyzed by Pd(OAc)2 and (R,R)- or (S,S)-DIOP (4, 273) in a 1 1 ratio. In this case, the tricyclic dienone (2) is obtained in... 

During the same year, Overman and co-workers synthesized spirocycle 5.14 in 90% yield with 45% ee by two sequential Heck cyclization of trienyl triflate 5.13 at room temperature in the presence of Pd(OAc)2-(R,R)-DIOP and Et3N in benzene. 

More common is use of intramolecular Heck reactions to fashion ckv-decalins. Several examples are found in our current program aimed at the total synthesis of complex cardenolides [14,15]. In a model study for a proposed synthesis of (-t-)-ouabagenin (48), trienyl triflate 45 was converted to pentacycle 47 in good yield (Scheme 6-8) [16]. The stereochemical outcome of this cyclization was rationalized by the preference for an eclipsed orientation of the two reacting bonds, which is readily achieved in a cyclization geometry (46), and led to the cis stereoisomer. This example also highlights the stability of... 

For nongroup-selective examples, one of the first reports of an enantioselective intramolecular Mizoroki-Heck reaction was a polyene cyclization (Scheme 12.22) [23b], The trienyl triflate 5 underwent two intramolecular cyclization reactions to give the tricycle 6 in high yield and 45% ee. A cascade intramolecular Mizoroki-Heck-hydride capture sequence was used in the synthesis of retinoid derivatives from aryl iodide 100 to give benzofuran 101 in 80-81% ee [49]. Poor enantioselectivity was observed when neutral reaction conditions were employed. 

Carpenter, N.E., Kucera, D.J. and Overman, L.E. (1989) Palladium-catalyzed polyene cycliza-tions of trienyl triflates. J. Org. Chem., 54, 5846-8. 

The use of carbanionic nucleophiles in the Mizoroki-Heck cyclization-/ -allyl nucleophilic trapping sequence allowed for streamlined access to the triquinane core common to various members of the capnellene family of natural products. For example, Shibasaki and coworkers obtained diquinane 57 in 77% yield and 87% ee by Mizoroki-Heck cy-clization of trienyl triflate 47 in the presence of malonate nucleophile 56 Scheme 16.14). It is notable that two new C-C bonds and three stereocentres are generated in this reaction. Eleven additional steps were used to convert intermediate 57 to ( )-A ( Ecapnellene (58). This first catalytic asymmetric total synthesis ( )-A d2). j pjjgjjgjjg achieved in 19 steps and 20% overall yield from commercially available materials. A related approach has recently been employed to prepare intermediates en route to capnellenols 53 and 54 (Scheme 16.12) [41]. 

After insertion of the palladium into the carbon-oxygen bond of the trienyl triflate 120, the (S)-BINAP (2,2 -bis(diphenylphosphinyl)-l,l -binaphthalene) ligand on the palladium led to selective coordination to one of the enantiotopic double bonds with subsequent cyclization to give the intermediate tt-allyl complex 124. This was regio- and stereoselectively trapped by the nucleophile. Further elaboration of 121 gave the natural product with good optical purity. 

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). 

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