Heck reaction eight-membered rings

In their studies toward the total synthesis of Taxol , Danishefsky and co-workers have focused their attention on the formation of eight-membered rings by an intramolecular Heck reaction proceeding by an -exo-trig cyclization of a 2-halo-1,8-decadiene system (Scheme 19, Table 14). 

The first example in Scheme 5.23 stems from the ( )-duocarmycin S A (127) synthesis by Natsume and coworkers [59] cyclization of 125 provided the expected product 126 in 82% yield along with 11% the isomeric enamine (not shown) (125 126, Scheme 5.23). In the Mizoroki-Heck reaction of 128, an eight-membered ring was exclusively tra 5-annulated in 64% yield, resembling a steroid-like polycyclic structure (128 129) [45, 60]. 

Two Heck reactions, the first intramolecular in an exo- sense, the second intermolecular, were used to prepare an intermediate 5.105 for a prostaglandin receptor antagonist on a 2.17 kg scale (Scheme 5.32). An intramolecular Heck reaction of a vinyl triflate 5.106 with an cxo-ring closure was employed to form an eight-membered ring in a synthesis of taxol (Scheme 5.33). ... 

For the construction of the crucial eight-membered ring of pacUtaxel via Heck cyclization, the vinyl iodide 434 has been used as an intermediate (Scheme 3.83) [135]. To obtain the secondary alcohol in a stereochemically pure form the addition of lithiated aryl bromide 435 to aldehyde 434 was investigated. It turned out that the presence or absence of a TMS-protecting group at the tertiary alcohol was crucial. Thus, TMS-derivative 434 gave a diastereomeric mixture of 436 and 437 after desilylation, whereas the reaction of the free alcohol 438 led to diastereomericaUy pure 440, presumably via a chelate 439 in which the quaternary carbon directs the nucleophilic attack to the opposite face. 

Ma and Negishi [41] also extended the scope of c do-selective Mizoroki-Heck reactions of allenes to the formation of medium-sized rings and macrocycles. A selection of representative reactions is depicted in Scheme 5.39. Cyclizations of precursors 228a and 228b provided the corresponding eight- and nine-membered rings in 56% and 62% yields... 

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