Palladium-catalyzed cascade cyclization reaction

After investigation of the palladium-catalyzed cascade cyclization/Suzuki coupling reactions of 1,6-enynes, Zhu and Zhang turned their attention to the analog 1,2,7-triene 333 for the synthesis of various functionalized five-membered cycles 334/335 [115] (Scheme 6.88). Oxidative addition of allyl hahides or carbonates to Pd(0) generates 7i-allylpalladium species 336, followed by intramolecular cycUzation to form vinylpalladium complex 337. Subsequent transmetallation with aryl boronic acids... 

Palladium-catalyzed cyclization reactions with aryl halides have been used to synthesize pyrazole derivatives. V-Aryl-lV-(c>-bromobenzyl)hydrazines 26 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2W-indazoles 27 . Palladium-catalyzed cascade intermolecular queuing-cyclocondensation reaction of o-iodophenol (28) with dimethylallene and aryl hydrazines provided pyrazolyl chromanones 29 <00TL7129>. A novel one-pot synthesis of 3,5-disubstituted-2-pyrazolines 32 has been achieved with an unexpected coupling-isomerization sequence of haloarene 30, propargyl alcohol 31, and methylhydrazine <00ACIE1253>. 

As an extension of the Heck reaction, Pd-catalyzed hydroarylation of alkynes and alkenes continnes to attract high level of research interest in simple couphng processes and in cyclization reactions. The use of this type of transformation as part of a domino reaction will be of increasing interest. The research in the field of domino reactions is attracting considerable attention in synthetic organic chemistry since it enables the rapid assembly of complex molecirles in one-pot processes. Very elegant examples of palladium-catalyzed cascade processes where a single catalytic cycle entails several sequential bond transformations have been recently reported [la, b, 2a, b, c]. 

Moreover, several resveratrol-derived natural products can be synthesized by a palladium-catalyzed cascade reaction of bromostilbene derivative 121 and tolane 122 (Scheme 60) (110). In this cascade reaction, intermolecular Heck reaction proceeds first, followed by intramolecular Heck cyclization to give the desired carbon framework of dimeric resveratrol natural products. 

A palladium-catalyzed intramolecular cyclization of enolate O-aiylation and thio-enolate S-arylation was reported by Willis and co-workers in 2006. A catalyst generated from Pd2(dba)3 and the ligand DPEphos effects the key bond formation to deliver a variety of substituted products from both cyclic and acyclic precursors. The analogous thio-ketones undergo C-S bond formation using identical reaction conditions and were converted to ben-zothiophene products. A cascade sequence that produces the required a-atyl ketones in situ has also been developed (Scheme 2.6). 

This type of cyclization reaction was applied in the synthesis of p-carbo-linones and total synthesis of dipyrrolobenzoquinone ( )-terreusinone as well. In 2005, Barluenga and co-workers reported a novel approach for the synthesis of indoles from o-bromoanilines and alkenyl halides via a palladium-catalyzed cascade process (Scheme 2.112). The reaction involves an alkenyl amination followed by an intramolecular Heck reaction. As the authors demonstrated, this process represents the first example of the participation of alkenyl amination reactions in Pd-catalyzed cascade reactions. Initially, the relative reactivity of aiyl and alkenyl bromides and chlorides towards Pd-catalyzed amination was investigated. Competition... 

Early in 1992, Negishi et al. reported a palladium-catalyzed cascade involving alkynes toward benzene derivatives [38], Recently, Blond et al. reported a palladium-catalyzed cascade reaction toward strained aromatic polycycles 100 [39] (Scheme 6.22). Bromoenediynes 98 undergo A-exo-dig cyclocarbopalladation and subsequent 5-exo-dig cyclization to afford the vinylpalladium intermediate 99, which possibly undergoes a 6n-electrocyclization and a syn 3-H elimination to furnish the products observed. 

An interesting palladium-catalyzed cascade reaction leading to 3,3-disubstituted oxindoles 190 starting from 2-(alkynyl)aryl isocyanates 189 with benzylic alcohols has been developed by Toyoshima et al. [76] (Scheme 6.53). This reaction integrates a cyclization step and a novel [1,3] rearrangement step. Both benzylic and allylic alcohols could be introduced efficiently to this domino process. Furthermore, the products of this reaction are an important class of heterocycles which are often found in naturally occurring and biologically active molecules. 

Gabriele et al. reported a sequential homobimetallic palladium-catalyzed cascade reaction for the synthesis of benzofuran derivatives 207 [80] (Scheme 6.57). Sequential homobimetallic catalysis is different in catalytic cycles promoted by the same metal but in different oxidation states. After oxidative addition and oxopalladation, 5-exo-dig cyclization occurs, followed by carbonylation, affording the intermediate 206. The allylic alcohol is reduced by H—Pd—I through formation of a ji-aUyl complex and the elimination of water. Finally, the product observed is afforded... 

The palladium-catalyzed cyclization reaction was used in the syntheses of several natural products such as siccanin [86], streptazolin [87], and ceratopi-canol (through a diyne, diene cascade) [80]. The production of the streptazolin precursor 149 through reductive cyclization of 150 is illustrative of the complexity that the reaction can provide (Eq. 29) [87]. 

Radical cyclization is an effective approach to the synthesis of isoquinolines (Scheme 8). In some cases these offer an alternative to the palladium-catalyzed reactions with aryl halide intermediates <99EJOC1925, 99TL1125>. For example, the radical cyclization of the iodide 37 onto the vinylsulfide moiety was followed by a cascade cyclization to form the benzo[n]quinolizidine system <99TL1149>. In some cases the radical cyclization can take place without the need for a halo intermediate. The reactive intermediate of 38 was formed on the nitrogen as an amidyl radical, which underwent tandem cyclizations to the lycorane system <99TL2125, 99SL441>. 

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... 

Neumann, A., Reglier, M. The stereochemistry of palladium-catalyzed cyclization reactions. Part C Cascade reactions. Tetrahedron 1996,... 

Some reaction sequences can also be orchestrated so that the first step provides an intermediate that triggers a subsequent conversion. Examples include tandem reactions [13], domino reactions [14], and cascade reactions [15], A comprehensive review of sequential transformations has been compiled by Tietze and Beifuss [16]. An example of the complexity produced by cascading palladium-catalyzed cyclizations [17] is shown in Figure 2.10. 

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