Enynes palladium catalysis

Bromoalkynes also couple with vinylstannanes readily to result in enynes. Synthesis of protected enynals via cross-coupling of vinylstannanes with 1-bromoalkynes in the presence of a catalytic amount of Pd(II) has been reported (equation 143)252. Hiyama and coworkers extended the Stille methodology for sequential three-component coupling of trimethylstannyl(trimethylsilyl)acetylene with a vinyl iodide in the first step and cross-coupling of the intermediate trimethylsilylethyne with another alkenyl iodide in the presence of tris(diethylamino)sulphonium trimethyldifluorosilicate in the second step to generate a dienyne (equation 144)253. Both steps occur under palladium catalysis, in one-pot, to result in stereodefined l,5-dien-3-ynes. 

Synthetic methods for the preparation of dienes and enynes abound, yet the use of alkenyl iodonium salts offers distinct advantages. Their coupling reactions with electron-deficient alkenes and alkenyl- or alkynylstannanes constitute a valuable extension to the previously existing methodology, because of mild conditions, ease of operation, high stereoselectivity and good yields. The simplest reaction of this category is with unsaturated carbonyl compounds and requires palladium catalysis. 

Intramolecular variants of the Alder-ene type couplings between alkynes and alkenes have been extensively explored by means of palladium catalysis [73]. Recently, such a cycloisomerization of enynes was also accomplished with ruthenium catalysis (Scheme 4.32) [74]. 

Transition metal catalysis is playing an ever increasing role in the synthesis of heterocyclic ring systems. Grubb s ruthenium catalyst is very effective in enyne metathesis of (10) in which the azepine (11) is formed in high yield <94SLI020> and molybdenum metathesis is used in the preparation of pyrroloazepine derivatives <94TL6005>. Palladium catalysis of the cyclisation of N,N-dimethyl-2-(r-acetoxy-2 -propenyl) benzylamines yields 2,3-dihydro-l//-2-benzazepinium (12) salts (Scheme... 

The utility of the platinum-catalyzed enyne cycloisomerization for the formal synthesis of Rosephilin, which is a member of prodiginine family of alkaloids, was reported by Trost and Doherty (Scheme 7.44) [94]. The critical step in the synthesis was the conversion of enyne 221 to bicyclic diene 222 by platinum-catalyzed enyne cycloisomerization. While palladium catalysis was found to be ineffective, the desired cyclopentene 222 was obtained when 221 was treated with the platinum-based catalytic system developed by Murai. Diene 222 was converted to tricyclic pyrrole intermediate 223 in an 11-step sequence. Since 223 had been converted to roseophilin 224, the entire procedure represented a formal synthesis of the alkaloid. 

As another example leading to novel conformationally restricted peptidomimetics, a Pd-catalysed enyne cycloisomerization was described as a route to macrocyclic diene structures (119, Figure 11.13, site of ring closure and palladium species indicated). Subsequent [4+2] cycloadditions with dienophiles then gave the target molecules. An interesting application of the use of palladium catalysis in macrocyclization was reported by Barnickel and... 

A cascade Michael/annulation process combining amino and palladium catalysis is shown in Fig. 8.27. In the first step, optically active chiral aldehydes are generated with a secondary amine catalyst, which followed by palladium-catalyzed enyne cycloisomerization. 

The synthesis of five-membered carbo- and hetero-cyclic compounds, including fused rings, has been reported using acetate as a nucleophile in the cyclization of 1,6-enynes under palladium(II) catalysis (Scheme 91). The reaction is initiated by trans-acetoxypalladation of the alkynes and quenched by either trans- or ra-deaceloxypal-ladation in the presence of 2,2/-bipyridine as the ligand.134... 

By the choice of the enyne substrates, the obtained cyclized products might contain functionalities other than dienes. The unusual catalyst combination of a Pd precatalyst and formic acid enables sequential catalysis initiated by cycloisomerization in a very peculiar way. Kressierer and Muller [16] demonstrated in several cases that the palladium(0)-catalyzed Alder-ene reaction of a-alkynyl M-allyl alcohols 7 furnishes cyclic y,5-enals 8 as a consequence of the in situ enol-aldehyde tautomerism (Scheme 12.2). 

Complementary to the palladium-catalyzed version, the [4 - - 2] homo-benzannulation of enynes under a cobalt catalysis was reported by Hilt group [12]. It was found that 4-substituted enynes formed the corresponding 1,6-disubstituted styrenes in moderate... 

In 2003, Oh and Lim reported a cascade route to exocychc dienes, using 2-bromo-l,6-enynes together with aryl- or vinylboronic acids under the catalysis of palladium salts [41 ] (Scheme 6.24). hi this case, no P-hydride elimination occurs because the intermediate vinylpalladium species does not contain any p-hydrides for elimination [42]. 

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