Heck-type cyclization

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(. 

Toyota, Ihara and coworkers [178] used a combination of a Wacker- and a Heck-type transformation to construct the cedrane skeleton. Thus, reaction of 6/1-374 using 10mol% Pd(OAc)2 under an atmosphere of 02 led to the domino product 6/1-375 in 30% yield. In addition, 58% of the mono-cyclized compound 6/1-376 was obtained (Scheme 6/1.94). 

It has been known for sometime that 2-(2-bromoanilino)enones undergo Heck-type cyclizations to form indoles and carbazoles. Thus, Kibayashi reported the synthesis of 4-keto-l,2,3,4-tetrahydrocarbazoles in this manner [362], and Rapoport employed this reaction (296 to 297) to achieve an improved synthesis of 7-methoxymitosene [363]. A series of related mitosene analogs has been crafted using Pd chemistry by Michael and co-workers [364], They found that P(o-tol)3 was far superior to PPh3 in conjunction with Pd(OAc)2. 

In the cyclization of the (iodoaryl)diene, N-methyl-N-(l,5-hexadiene-3-yl)-2-iodobenzoic acid amide, the combined yield of the tricyclic products arising from a double intramolecular Heck reaction reached 52 % when the catalyst was prepared from [Pd(OAc)2] and 1,10-phenanthroline and the reaction was run in ethanol/water 1/1 (Scheme 6.4) [18,19]. Interestingly, in CH3CN the reaction did not proceed at all with this catalyst. It is also noteworthy, that Pd-phenanthroHne complexes are rarely used as catalysts in Heck-type reactions. 

Construction of the azepine ring by C-C bond formation. The Heck-type cyclization of amides 11, easily available by amide bond coupling (EDCI, DMAP) between the corresponding indolo- and pyrrolo-[2,3- 7]p)uidine-carboxylic acids and 2-iodobenzylamine, is effective in the presence of Pd(OAc)2/PPh3 catalyst and silver carbonate base and leads to excellent yields of the corresponding azepinones 12 (Equation (1) (2005TL8177)). 

Heck-type cyclization of oxime ethers which contain a halogenated aryl group is a new route to dihydroindole oxime ethers. Thus, oxime ethers 70 in the system Pd(PPh3)4/ K2C03/dioxane afforded dihydroindoles 71 in 59-89% yields (equation 30) °. ... 

Co-Cyclizations and Cascade Oligocyclizations by Multiple Heck-type Reactions 322... 

The formation of compound 175 could be rationalized in terms of an unprecedented domino allene amidation/intramolecular Heck-type reaction. Compound 176 must be the nonisolable intermediate. A likely mechanism for 176 should involve a (ji-allyl)palladium intermediate. The allene-palladium complex 177 is formed initially and suffers a nucleophilic attack by the bromide to produce a cr-allylpalladium intermediate, which rapidly equilibrates to the corresponding (ji-allyl)palladium intermediate 178. Then, an intramolecular amidation reaction on the (ji-allyl)palladium complex must account for intermediate 176 formation. Compound 176 evolves to tricycle 175 via a Heck-type-coupling reaction. The alkenylpalladium intermediate 179, generated in the 7-exo-dig cyclization of bro-moenyne 176, was trapped by the bromide anion to yield the fused tricycle 175 (Scheme 62). Thus, the same catalytic system is able to promote two different, but sequential catalytic cycles. 

The Heck reaction has now been reviewed448,449. Evidence for the formation of zerova-lent palladium from (AcO Pd and Ph3P via a redox process has been provided450. This explains the origin of Pd(0) required for certain palladium-catalysed reactions in cases where Pd(II) is added to the reaction as the primary form of the Pd-catalyst. Thallium has been found to accelerate the Heck-type cyclization-carbonylation451. 

The Ni-catalysed Heck reaction is rather rare. Although the attempted Ni(0)-catalysed cyclization of iodide 107 gave a mixture of many products, the pentacyclic nitrone 108 was isolated in 40% yield by the domino Heck-type reaction, reductive... 

Optically active cis-decalins can be obtained from substrates such as 4 by a Heck-type reaction with PdCl2/(R)-l (1 1) as the catalyst.8 Addition of various silver salts improves the yield and enantioselectivity. For cyclization of 4 to 5, the highest enantioselectivity was observed by use of Ag3P04 and CaC03 (2 equiv. of each) with 1 -methyl-2-pyrrolidinone (NMP) as solvent (60°). 

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... 

Fu et al. recently presented their results on carbene-catalyzed intramolecular Heck-type cyclizations [68]. The N-heterocyclic carbene generated in situ from the triazolium salt 83 catalyzed cyclization of the substrates 84 to form the cycloalkanes 85 (Scheme 9.25). The lowest yields were obtained when the reaction products were cyclobutanes. These authors assumed that the carbene initially reacted with the Michael acceptor site of the substrate to the intermediate 86, which subsequently cyclized via 86 to the final products 85. 

The palladium-catalyzed arylation and alkenylation of olefins, which were first discovered in the 1970 s by Heck (7,2) and Mizoroki (3) and have been often called the "Heck reaction", are versatile synthetic means for making a carbon-carbon bond. These reactions have been extensively used for organic synthesis during the past two decades (4-7). However, no reports on the "asymmetric Heck reaction" have been appeared until very recently. Shibasaki reported an asymmetric intramolecular cyclization of alkenyl iodides to give c/j-decalin derivatives of 80-91% ee (8-10). Overman reported an intramolecular cyclization of alkenyl triflate, giving a chiral quaternary carbon center of 45% ee (77). We report herein the first example of intermolecular asymmetric Heck-type arylation of cyclic olefins catalyzed by (7 )-BINAP-coordinated palladium complexes (Scheme 1) (12,13). 

Radical cyclization (Redox-neutral, Heck-type) 1 Mn(0) 9.2... 

Fig. 48 Pd(0)-cataIyzed thermal carbonylative Heck-type cyclization reactions...

A Heck-type cobalt-catalyzed cyclization of 6-halo-1-hexenes into 3-... 

Grigg et al. also introduced another Heck-type reaction. 2,6-Dibromo-hepta-1,6-dienes 80 cyclize to the same products 83 (n = 5) as do 2-bromo-1,6-dienes 78 (n = 5) when treated with the usual precatalyst mixture, yet containing a stoichiometric amount of triphenylphosphine [63,64], In this case, palladium dibromide rather than hydridopalladium bromide is eliminated in the final step of the cross-coupling reaction, and the palladium(II) salt is reduced by the phosphine to regenerate the reactive palladium(O) species. Completely selective exo-trig cyclizations occur in these examples, however, the respective cyclohexane derivatives with n = 6 are formed in poor yields. Additionally, it is sometimes difficult to separate the product from the phosphine oxide after aqueous work-up. This latter difficulty was circum-... 

Another example features a Heck-type 5-exo-trig cyclization of the aryl iodide 139 occurring at room temperature in dichloromethane (Scheme 22) [82], Azomethine ylides originating from imines 133 were used to trap the Heck product 140 in a subsequent 1,3-dipolar cycloaddition. The diastereomeric products 141 and 142 both derive from an endo attack of... 

Because many 4-benzylpiperidines are physiologically and pharmacologically active, an efficient route to these compounds was developed <03TL8249>. Cyclization of imines containing an allylsilane with aldehydes in a one-pot reaction resulted in 4-methylenepiperidines in good yields. Heck-type arylation of arylboronic acids with 4-methylenepiperidines afforded the styryl derivatives, which gave the desired piperidines on reduction. 

A wide variety of synthetic processes have been rendered asymmetric through the use of a chiral catalyst. In addition to the types of reaction described above, chiral transition metal catalysts have been used to influence the stereochemical course of isomerization, cyclization, and coupling reactions. As an example, an approach towards the natural product (-)-epibatidine (158) was recently reported by Namyslo and Kaufmann (166). Epibatidine is a potent analgesic and a nicotinic receptor agonist. The synthesis involves an asymmetric Heck-type hydroarylation between the bicyclic alkene (155) and pyridyl iodide (156). A number of bidentate chiral li-... 

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