Dienes intramolecular coupling

The intramolecular coupling of organostannanes is applied to macrolide synthesis. In the zearalenone synthesis, no cyclization was observed between arylstannane and alkenyl iodide. However, intramolecular coupling take.s place between the alkenylstannane and aryl iodide in 706. A similar cyclization is possible by the reaction of the alkenylstannane 707 with enol triflate[579]. The coupling was applied to the preparation of the bicyclic 1,3-diene system 708[580]. 

Suitably positioned vinyl halide can undergo Heck-type intramolecular coupling to generate dienes (equations 124 and 125)216,217. When one of the reacting partners in the Heck reaction is a diene, trienes are obtained (equation 126)218. Heck coupling of ally lie alcohols and alkenyl iodides has been employed for the synthesis of vitamin A and related compounds (equation 127)219,220. A similar double Heck reaction on a Cio-diiodide with a Cis-allylic alcohol leads to -carotene as a mixture of isomers (equation 128)209e. 

In Section 9.2, intermolecular reactions of titanium—acetylene complexes with acetylenes, allenes, alkenes, and allylic compounds were discussed. This section describes the intramolecular coupling of bis-unsaturated compounds, including dienes, enynes, and diynes, as formulated in Eq. 9.49. As the titanium alkoxide is very inexpensive, the reactions in Eq. 9.49 represent one of the most economical methods for accomplishing the formation of metallacycles of this type [1,2]. Moreover, the titanium alkoxide based method enables several new synthetic transformations that are not viable by conventional metallocene-mediated methods. 

Anodic C, C-coupling is a very powerful tool to synthesize cyclic compounds with high regio- and stereoselectivity. It involves inter- and intramolecular coupling of arylolefins, dienes, enolethers, phenol ethers, and aromatic amines and often opens a quick entry into complex natural products in a few steps. Although the mechanism is fully established in only a few cases, it does appear to involve the coupling of two radical cations at the site of their highest radical density and is further controlled by steric constraints. This important type of reaction is reviewed in Chap. 5 and in Refs. [89, 90]. 

Coupling of vinyl bromides 1,3-dienes.3 Vinyl bromides can undergo inter-or intramolecular coupling to 1,3-dienes in the presence of Pd(OAc)2, a triaryl-phosphine (1.25 equiv.), and a large excess of K2C03 (7.5 equiv.). 

The catalytic intramolecular coupling of two C=C bonds at a ruthenium site leads to cyclization reactions. For example, although generally less reactive than a,co-diynes or enynes, 1,6-dienes react with [RuC12(COD)] in 2-propanol, leading to exo-methylenecyclopentanes in excellent yields [13] (Eq. 8). The mechanism suggests the formation of the ruthenacyclopentane(hydrido) intermediate 19. 

The ruthenium-catalyzed cycloisomerization of a variety of <5-enallenes was also achieved, forming cyclic 1,3-dienes or 1,4-dienes depending on the substrates and reaction conditions [32] (Eq. 22). This intramolecular coupling of the C=C bond and allenes can be envisioned by the initial hydrometallation of the allene moiety followed by intramolecular olefin insertion and isomerization. 

Similarly, Mori and coworkers [127] have demonstrated that stannanylsi-lanes such as Bu3SnSiMe3 can be applied for the intramolecular coupling of vinyl triflates with a tethered vinyl bromide, as in compound 175, to give cyclic dienes 176-181 (Scheme 67). 

A number of intramolecular coupling reactions that involve reductive cyclization of a (cyclohexadiene)Fe(CO)3 complex that bears a pendant alkene or diene have been reported. Under CO atmosphere, this unusual cyclization presumably produces an intermediate r] -7t-d y complex that then rearranges via hydride migration. In the case of the pendant diene, a second such process can occur (Scheme 68). 

A number of new Ni-catalyzed protocols have been developed recently for the coupling of carbonyl compounds and unsaturated substrates such as alkynes or 1,3-dienes. For instance, a three-component intramolecular coupling (alkyne/aldehyde/hydrosUane) has led to the formation of bicyclic N-heterocycles. A number of similar inter- and intramolecular coupling reactions have been developed into useful synthetic routes (Scheme 27). 

Piers and Wong [209] used intramolecular coupling between an alkenyltin and an alkenyl halide moiety to form a cyclic conjugated dienes in the presence of 2-3 equiv. of CuCl in... 

Intramolecular couplings between nonconjugated double bonds being suitably disposed for transannular reactions have been carried out with norbornadiene (XXII, / = 1 Table 7, number 7) and bicyclo[2.2.2]octa-2,5-diene [142]. 

Suitably positioned vinyl halide can undergo Heck-type intramolecular coupling to generate dienes (equations l24 and When one of the reacting partners in the... 

Intramolecular coupling of 120 having an aryl iodide group and a vinylstannane group accomplished the total synthesis of (-)-zealarenone (99) (Scheme 19) [77]. The first total synthesis of macrolactin A (124) was efficiently accomplished based on the Stille reaction of 122 for both stereospecific construction of the diene moieties and closure of the 24-membered macrocyclic ring [78]. The key precursor 122 was synthesized via two Stille couplings and Mitsunobu esterification. An alternative route to the dimethyl ether 125 was reported by cyclization of 123, which was prepared by the Stille and Suzuki couplings followed by DCC-DMAP esterification... 

Coupling of aryl and benzylic halides. Grigg has extended the inter- and intramolecular coupling of vinyl bromides to form 1,3-dienes catalyzed by Pd(OAc>2-triphenylphosphine (13,234) to coupling of aryl and benzylic halides by the combination of a Pd(0) catalyst and [(CH3)3Sn]2 or (Bu3Sn)2 (1 equiv.). 

This conversion of an acyclic bisdiene to a cychzed enediene constitutes a new Pd-mediated reaction mode, which can be rationalized as outlined in Scheme 7. Com-plexation of bisdiene 17 following oxidative cyclization (i.e., oxidative addition with intramolecular coupling of the diene moieties) affords palladacycle 20. Protonation in an... 

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