Cascade reaction palladium-mediated

Access to optically active 2-fluoro-l-tetralone 53 was achieved using the same palladium-mediated cascade reaction [30]. The catalytic enantioseiective decarbox-ylative protonation of 2-fluoro benzyl P-keto ester 54 in the presence of 30 mol% of quinine 20 afforded enantioenriched (S)-tetralone 53 in 65% ee (Scheme 7.24). The reaction was very sensitive to the nature of the palladium catalyst used. Furthermore, a minor amount of defluorinated product was observed. Several other cinchona derivatives were tested including analogues of cinchonine described by Brunner in organocatalytic EDP (see Section 7.5.3), but these chiral inductors afforded low selectivities (<30% ee). 

Grigg and co-workers described a novel three-component indium-palladium-mediated allylation reaction [67]. As exemplified by Eq. 14.16, 3,3-disubstituted oxi-ndole derivative 133 was obtained smoothly from phenyl iodide, the easily available isatin imine 132 and 1,2-propadiene (131). Excellent levels of diastereoselectivity were obtained in this cascade reaction employing imines derived from enantiopure sulfmamides. 

Tab. 8.12 Indi um-mediated palladium-catalyzed cascade reaction with allene...

Figure 8.3 Selectively substituted heteroatom-containing bicyclic, tricyclic, and higher oligo-cyclic systems assembled in norbornene-mediated palladium-catalyzed cascade reactions [363-366].

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... 

This indium-mediated palladium-catalyzed Barbier-type allylation of aldehydes is expanded to cascade reactions with allenes, which give three-component coupling products (Tab. 8.12 and 8.13) [89]. 

As depicted below, a procedure for the iodocyclization of acetoxy-containing 2-(l-alkynyl)anisole and subsequent direct palladium-catalyzed earbonylatiori/lactonization was reported as an efficient entry to naturally occurring eoumestan and coumestrol <05IOC9985>. A novel Pd(II)-mediated cascade carbonylative annulation of substituted o-hydroxyphenylacetylenes to give benzo[fo]furan-3-carboxylie adds was achieved in a one-pot reaction <050L2707>. 

Ruthenium-mediated regioselective intermolecular homo- and heterodimerization of substituted propiolates leads to 2H-pyran-2-one-5-carboxylates and 2H-pyran-2-one-6-carboxylates (140L652). 6-Aryl-2J-f-pyran-2-ones arise from a palladium-catalyzed oxidative aimulation of internal alkynes with acrylic acid with excellent regioselectivity and in high yields (140L2146). A one-pot isothiourea-promoted cascade reaction of (phenylthio) acetic acids with a,P-unsaturated trifluoromethyl arylke-tones provides 4-aryl-6-trifluoromethyl-2f/-pyran-2-ones (Scheme 42) (140L964). 

Diunsubstituted coumarins are available from the palladium(II)-catalyzed intermolecular annulation reaction of phenols with methyl acrylate (13AGE12669) and from an organocatalytic cascade reaction of salicylalde-hydes with malonic acid half-thioesters mediated by a combination of ben-zylamine and triethylamine (Scheme 60) (13EJ04499). 

Palladium chemistry has been used in the synthesis of tetrahydroisoquinolines. Different combinations of iodoaryl-amine-alkene can be used in these multicomponent reactions. For example, the metal-mediated o-alkylated/alkenyl-ation and intramolecular aza-Michael reaction (Scheme 109) give moderate yields of heterocycle <2004TL6903>, whereas the palladium-catalyzed allene insertion-nucleophilic incorporation-Michael addition cascade (Equation 172) produces good yields of tetrahydroisoquinolines in 15 examples <2003TL7445> with further examples producing tetrahydroquinolines (Scheme 110) <2000TL7125>. 

In an interesting extension. Oh has recently shown that palladium complexes can be used to catalyze the cascade cyclization of 23 to furan derivatives [56]. This reaction presumably involves the initial generation of a palladium-hydride bond under the reaction conditions, which can mediate sequential insertion of the alkyne units to... 

In many of the previous cases, palladium is the sole mediator of the reaction. Xiao and collaborators, however, found a catalytic two-bond-forming reaction that furnishes 1-indanones with the aid of a solvent [45]. The Heck-aldol-type cascade allows a great variety of aryl aldehydes/ketones in combination with an array of enol inputs (Scheme 14.24). The product contains the indan scaffold of the antibacterial pterosin C, which is also found in a diverse set of marketed drugs, for example, (-E)-indacrinone (hypertension) and donepezil (HIV protease inhibitor). 

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