Heck reaction seven-membered rings

Dimethyl iodo(4-pentenyl)malonate (926) undergoes a Pd-catalyzed intramolecular radical-type reaction to form the alkyl iodides 927 and 928. rather than a Heck-type reaction product(775]. The same products are also obtained by a radical reaction promoted by tin hydride(776]. Although yield was low, a similar cyclization of the n-chloro ester 929 to form the seven-membered ring 930 was ob,served(777(. 

TV-substituted methylenephthalimide derivatives served as the starting material for the preparation of a series of tetracyclic systems. The intramolecular Heck reaction of these compounds (4.10.) led in each case to the formation of a carbon-carbon bond between the exocyclic carbon atom of the olefin bond and the aryl moiety. The formation of five, six and seven membered rings was achieved with near equal efficiency, enabling the preparation of some isoindolobenzazepine alkaloids.11... 

A similar palladium-catalyzed process involving an intramolecular Heck-type reaction in the first step was developed by Grigg and co-workers [70], The resulting seven-membered ring vinylpalladium(II) intermediate 54 reacts with the allene to... 

The intramolecular Fujiwara-Moritani/oxidative Heck reaction was applied to the synthesis of functionalized benzo[fe]furans and dihydrobenzo[h]furans in 50-80% yields, and 15 examples are given in the article <04AG(E)6144->. Ionic liquid ([bmimJBF4) was found to be an effective solvent for the PdCl -catalyzed intramolecular Heck reaction to realize benzofurans <04TL6235>. Another palladium-catalyzed intramolecular Heck reaction between vinyl triflate and benzo[(j]furan was utilized to construct the seven-membered ring based (-)-frondosin B <04T9675>. 

Aryl iodides are more reactive towards oxidative addition than aryl bromides, and a selective Heck coupling (without phosphine ligands) with an unsaturated side chain left the bromide in place. A second Heck reaction of this bromide with an allylic alcohol was used to introduce a second side chain. Cyclization of the amide on to the allylic alcohol was achieved with palladium catalysis, not as might have been expected with palladium(O) but instead with palladium(ll), to produce the seven-membered ring. Finally, the conjugated double bond was reduced and the sulfonamide removed under photolytic conditions. 

The synthesis of fused oxepines by transition metal-catalyzed reactions continues to be a major method for the formation of this heterocyclic system and can be separated into two types of transformations, those that react as tethered ethers and those that involve the reaction of an alcohol to form the seven-membered ring. The cyclization of tethered ethers included Heck cyclization (14EJO4053, 14CEJ17119), rhodium-catalyzed arylation of alkynes... 

Mizoroki-Heck cyclization of 198 was part of the studies towards the total synthesis of taxol (224) (see Scheme 5.38) by Danishefsky and coworkers [84] (198 199, Scheme 5.35). The strained seven-membered ring is formed in the presence of the hydroxyketone moiety in 52% yield and unconsumed 198 was re-isolated quantitatively. Danishefsky and coworkers [85] employed the high-yielding Mizoroki-Heck reaction of200 to assemble the bridged carbon skeleton in 201, an intermediate en route to the synthesis of CP-225,917 (202) and related CP-263,114 (not shown), which are squalene synthetase and famesyl transferase inhibitors (200 201). 

The seven membered core of iboga alkaloids has also been constructed in an intramolecular Heck reaction. Insertion of a pendant olefin into the indolylpalladium complex, formed from iodoindole, followed by / -hydride elimination gave the complex framework of the natural product (5.5.), Although the insertion step could have led to the formation of a six membered ring, the formed palladium complex would have contained a quaternary carbon center in the -position, blocking the closure of the catalytic cycle under the applied conditions.5... 

Tethering an iodobenzene and a furane moiety through a y0-lactam led to the formation of a unique tetracyclic y0-lactam derivative (5.17.). Oxidative addition followed by the carbopalladation of the furane ring resulted in the closure of the seven membered core in a so called heteroaryl Heck reaction "... 

As illustrated in Equation (182), a seven-membered lactam was formed by utilizing a ring closure reaction under Heck coupling conditions <20070BC655>. 

The preparation of seven-membered heterocycles via intramolecular Mizoroki-Heck reaction is by far not as frequent as the syntheses of five- and six-membered rings. There are, however, some examples, although these reactions started to be properly explored only in the late 1990s. The substrate substructures which one often comes across are summarized in Figure 6.5. 

The ring expansion of oxyglycal-derived gm-dihalo 1,2-cyclopropanate oxyglycals provides stable seven-membered halo-oxepines, that are thus suitable precursors for further functionalizations. In a study, vinyl bromide of the bromo-oxepine was used for the metal-catalyzed cross-coupling reactions, namely, Heck, Suzuki, and Sonogashira reactions, so as to generate 2-deoxy-2-C-alkyl/ary/alkynyl septanosides [33]. 

---