Palladium complexes cycloisomerization

Another useful class of palladium-catalyzed cycloisomerizations is based on the general mechanistic pathway shown in Scheme 13. In this chemistry, a hydridopalladium acetate complex is regarded as the catalytically active species.27b-29 According to this pathway, coordination of a generic enyne such as 59 to the palladium metal center facilitates a hydropalladation reaction to give intermediate 60. With a pendant alkene, 60 can then participate in a ring-form-... 

Although the conversion of 63—>67 adequately expresses the utility of palladium-catalyzed cycloisomerizations for the construction of complex polycycles, the single-step, palladium-mediated conversion of compound 68 to the novel polyspirocycle 6930,31 (Scheme 15) can perhaps be regarded as the paragon of this chemistry. In this striking transformation, chemo- and regioselective... 

The palladium complexes are the catalysts of choice for the cycloisomerization of the bisdienes, 9 which lead to the formation of either five- or six-membered enedienes with frarct-stereorechemistry for the vicinal substituents in the newly formed ring in high yields (Scheme 102).370... 

A multi-step asymmetric synthesis of a hydrindane framework was achieved in water via asymmetric allylic alkylation, propargylation and aquacatalytic cycloisomerization of a 1,6-enyne, where all three steps were performed in water with the recyclable polymeric catalysts. The racemic cyclohexenyl ester 27 reacted with diethyl malonate under the conditions mentioned in Table 6.1 to give 90-92% ee of 34b. The polymeric chiral palladium complex 23-Pd was reused four times... 

An impressive example of the possibilities of metal complex photochemistry is the substantiation of the critical step in corrin synthesis reported by Eschenmoser 145> Ring closure is brought about by antara-facial cycloisomerization of a secocorrinoidic palladium complex by photochemical 1.16-hydrogen shift. 

Pioneering the field of metal-catalyzed cycloisomerizations, Trost and his group was also the first to discover the power of cycloisomerizations in the total synthesis of complex natural structures. In 1999, he reported the first-and second-generation strategy for the synthesis of picrotoxane core structure through a palladium-catalyzed cycloisomerization [71]. 

Beside ene-type cyclizations, chiral phosphine-palladium complexes have been applied to only a few cycloisomerization processes, leading to 6-membered compounds. In aU these reactions SEGPHOSs are the preferred Ugands (Fig. 10.11). 

Goeke A, Kuwano R, Ito I, Sawamura M (1996) Enantioselective cycloisomerization of 1,6-enynes catalyzed by chiral diphosphane-palladium complexes. Angew Chem Int Ed 35 662-663... 

Jt-allyl complex can be generated after cyclization, as suggested by Takacs in a Fe(0)-catalyzed cyclization of polyenes. It also can be preformed if an active functional group is present in the allylic position. The palladium-catalyzed intramolecular cycloisomerization reaction of allylic acetates is an efficient method for constructing five- or six-membered rings [56, 57]. An asymmetric approach to this transformation has been studied and so far only poor enantioselectivity has been achieved (0-20% ee) [58]. Very recently, Zhang et al. also reported a Rh-catalyzed cycloisomerization involving a Jt-allylrhodium intermediate formed from an allylic halide [59]. 

Abstract This review gives an insight into the growing field of transition metal-catalyzed cascades. More particularly, we have focused on the construction of complex molecules from acyclic precursors. Several approaches have been devised. We have not covered palladium-mediated cyclizations, multiple Heck reactions, or ruthenium-catalyzed metathesis reactions because they are discussed in others chapters of this book. This manuscript is composed of two main parts. In the first part, we emphasize cascade sequences involving cycloaddition, cycloisomerization, or ene-type reactions. Most of these reaction sequences involve a transition metal-catalyzed step that is either followed by another reaction promoted by the same catalyst or by a purely thermal reaction. A simple change in the temperature of the reaction mixture is often the only technical requirement to go from one step to another. The second part covers the cascades relying on transition metalo carbenoid intermediates, which have recently undergone tremendous... 

Finally, the intramolecular cycloaddition methodology also provides access to heterocyclic systems when methylenecyclopropanes with heteroatom-containing side chains are employed. However, as shown above, very complex structural requirements are deary operable. For example, methyl 4-[(l-methyl-2-methylenecyclopropyl)methoxy]but-2-ynoate only yields a complex product mixture mainly containing conjugated dienes (arising from a ring cleavage/ -elimination sequence) upon attempted palladium(0)-catalyzed cycloisomerization. ... 

R. A. Widenhoefer, Synthetic and mechanistic studies of the cycloisomerization and cyclization/hydroxylation of functionalized dienes catalyzed by cationic palladium(II) complexes, Acc. Chem. Res., 35 (2002) 905-913. 

A range of cyclization and cycloisomerization reactions of enynes, including enynes with heteroatoms in the skeleton, have been reported for which the possibility of Pd(IV) intermediates has been canvassedJ f t t A typical example is shown in Scheme 16, where supporting ligands at palladium include palladacyclopentadienes, acetate, acetate/PPhj, and acetate/P(o-tol)3. An alternative pathway involving a Pd(0)-Pd(II) cycle has been acknowledged (Scheme 16), and different reaction conditions may favor each pathwayJ Alkylidene complexes as intermediates have also been proposed for some reactions of enynes... 

Cycloisomerization of enynes has been employed to construct an array of natural products.f " Although the precise mechanistic details of the reaction have not been elucidated, and may vary from case to case, one potential mechanism is shown in Scheme 28. Generation of an alkyl- or hydridopaUadium complex in the presence of enyne 183 may lead to carbo- or hydridopalladation to give an alkenyl palladium intermediate 184. Intramolecular cyclization (184 185) then follows to form five-, six-, or seven-membered rings followed by /3-hydride elimination to yield 1,4-diene 186 and/or 1,3-diene 187. There are also examples of yne-yne cyclizations in natural product synthesis. ... 

Cycloisomerization of dienes is also possible. Catalysts that have been used include rhodium (Scheme 11.80), ° ruthenium and palladium salts (Scheme 11.81) in alcohol solvents. Palladium NHC complexes are also efficient catalysts.The most likely mechanism involves the formation of a metal hydride, which acts as the catalyst. In some cases, alkene migration may also be observed and, with the right choice of catalyst, may become the exclusive pathway, as in the formation of cyclopentene 11.242. ... 

Complexation of triynes to Pd(0) has been reported to give homoleptic palladium alkyne complexes that show a trigonal-planar arrangement with all of the alkyne carbons and Pd in the same plane. Complex 73 is a macrocyclic complex synthesized by reaction of the triyne with Pd(PPh3)4- Due to coordination to the metal, the alkyne carbons are shifted to the center of the cycle and their substituents deviate from linearity by about 22°. Complex 74 undergoes clean intramolecular cyclization at room temperature upon addition of PPh3 (Equation (24)). No intermediate complexes were detected in the course of this reaction, which is an example of the important cycloisomerization of alkynes and enynes catalyzed, among other transition metal complexes, by Pd(0) derivatives. 

A final example in this section is isoquinolone formation via 6-endo-dig cycloisomerization (Scheme 19.77). Sashida and Kawamukai reported the palladium-catalyzed cyclization of 2-ethynylbenzamides 281 giving rise to isoquinolones 282 in good yields, similar to the aforementioned isocoumarin formation [143]. Ruthenium complexes are also useful for this transformation [146]. Recently, a 6-endo-dig cyclization/oxidative Heck coupling cascade of283 was also reported [147]. 

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