Palladium® complexes intermolecular Heck reaction

In 2004, Molander et al. developed another type of chiral sulfur-containing ligands for the intermolecular Heck reaction. Thus, their corresponding novel cyclopropane-based phosphorus/sulfur palladium complexes proved to be active as catalysts for the reaction between phenyltriflate and dihydrofuran, providing at high temperature a mixture of the expected product and its iso-merised analogue (Scheme 7.7). The major isomer C was obtained with a maximum enantioseleetivity of 63% ee. 

The intermolecular asymmetric Heck reaction, a palladium-catalysed carbon-carbon bond forming process, is an efficient method for the preparation of optically active cyclic compounds.[1] Very recently, a new catalytic system has been developed based on palladium complexes having l-[4-(5)-tert-butyl-2-oxazolin-2-yl]-2-(5)-(diphenylphosphino)ferrocene (1) as the chiral ligand121 (Figure 5.2), which we have shown to be efficient catalysts for the enantioselective intermolecular Heck reaction of 2,3-dihydrofuran (2).[3] In contrast to complexes derived... 

The JOSIPHOS ligand formed active complexes with palladium for opening of cyclic anhydrides (263) and the intermolecular Heck reaction (264). 

A few additional Pd-catalyzed schemes have been employed for Ilac type cyclization chemistry. Palladium-phenanthroline complexes were used by the Ragaini group to prepare indoles via the intermolecular cyclization of nitroarenes and alkynes in the presence of carbon monoxide <06JOC3748>. Jia and Zhu employed Pd-catalysis for the annulation of o-haloanilines with aldehydes <06JOC7826>. A one-pot Ugi/Heck reaction was employed in the preparation of polysubstituted indoles from a four-component reaction system of acrylic aldehydes, bromoanilines, acids, and isocyanides <06TL4683>. 

The Heck reaction, a palladium-catalyzed vinylic substitution, is conducted with olefins and organohalides or pseudohalides are frequently used as reactants [15, 16], One of the strengths of the method is that it enables the direct monofunctionalization of a vinylic carbon, which is difficult to achieve by other means. Numerous elegant transformations based on Heck chemistry have been developed in natural and non-natural product synthesis. Intermolecular reactions with cyclic and acyclic al-kenes, and intramolecular cyclization procedures, have led to the assembly of a variety of complex and sterically congested molecules. 

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). 

Guiry and coworkers [19] reported the preparation and testing of 2,2-dimethyl-2,3-dihydrofuran (22) as an interesting substrate for the intermolecular asymmehic Mizoroki-Heck reaction as this substrate only forms the one regioisomeric product 23. This allows for a true comparative test of a range of palladium complexes, and (7 )-BlNAP... 

To date, the large majority of asymmetric Mizoroki-Heck reactions reported have utilized palladium complexes of BINAP (5). However, since their first application to the asymmetric Mizoroki-Heck reaction, P,N ligands have proven successful and have thus received a greater amount of attention recently [30], The phosphinooxazoline PJSl ligands 41-45 developed independently by the groups of Pfaltz [31], Williams [32] and Hehnchen [33] have shown dramatic improvement in enantioselectivity in a number of asymmetric transformations, including the intermolecular asymmetric Mizoroki-Heck reaction [34]. 

In 2001, Mauleon et al. reported an unusual palladium-cascade arylation of a,P-unsaturated phenyl sulfones 23 under Heck reaction conditions [12]. Contrary to the work of Fuchs and others [13], Mauledn et al. described the intermolecular reaction of a,P-unsaturated sulfones with a large excess of iodobenzene (or / -substituted iodoarenes) in the presence of Ag COj as base, which occurred mainly through a complex cascade reaction in which three molecules of iodobenzene and one molecule of vinyl sulfone were involved, forming fused polycyclic compounds 25 rather than the Heck trisubstituted olefin expected. The authors propose a mechanism involving Heck reaction and C-H activation pathways (Scheme 6.5). 

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