Palladium catalysis cycloisomerization

Keywords Allylic substitution CH activation Cross-coupling Cycloisomerization Domino reactions Metallation Multicomponent reactions 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]. 

While furans have been the main focus of palladium-catalyzed allene cycloisomerization, pyrroles can also be generated via reaction of allenyl-substituted amines. A number of metal catalysts have been reported to mediate the cyclization of these substrates to pyrrolines, however, the use of palladium catalysis can allow the concomitant incorporation of aryl functionality into the 3-position, as shown in Scheme 6.27. At elevated temperatures, oxidation of the pyrroline occurs to afford pyrroles [37]. 

SCHEME 7.43 Improvement of diene cycloisomerization with hydrosilane additives under palladium catalysis. 

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. 

Moreover, following the cycloisomerization reaction, a tandem dimerization reaction is also possible on the same substrates under Pd11, Ag1, and Aura catalysis, leading to different substituted furans (4 or 6) depending on the nature of the catalyst used (Scheme 5.5). Indeed, from compound 3 (Scheme 5.5), palladium(II) catalysis led to a 59% yield of 4, whereas silver(I) and gold(III) catalysis led to furans 5 and 6.41... 

The cycloisomerization of a-allenyl ketones to the corresponding substituted furans was the first example of a gold-catalyzed addition of an oxygen nucleophile to an allene (Scheme 4-86). Traditionally, silver or palladium catalysts were employed for cyclizations of this type advantages of gold catalysis incluiie shorter reaction times, milder conditions, an or lower catalyst loadings. Variable amounts of... 

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). 

Xu et al. in 2013 exploited the synthesis of tetrasubstituted furan carboxylates using a tandem cycloisomerization/carbonylation sequence of cyclopropenes [22]. In the presence of palladium and copper, this tandem metal relay catalysis... 

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