Palladium domino reaction

The double-Heck-approach can also be employed for the preparation of novel heterocyclic compounds as 6/1-25 and 6/1-26 (Scheme 6/1.4) [24]. Thus, the palladium-catalyzed reaction of 6/1-21 and the cyclic enamide 6/1-22 gave a Oil-mixture of 6/1-23 and 6/1-24, which in a second Heck reaction using the palladacene 6/1-15 led to 6/1-25 and 6/1-26 in an overall yield of 44—49%. The synthesis can also be performed as a domino process using a mixture of Pd(OAc)2 and the palladacene 6/1-15. 

Based on a transformation described by Catellani and coworkers [61], the Lautens group [62] developed a three-component domino reaction catalyzed by palladium for the synthesis of benzo annulated oxacycles 6/1-114 (Scheme 6/1.30). As substrates, these authors used a m-iodoaryl iodoalkyl ether 6/1-113, an alkene substi-... 

Scheme 6/1.58. Domino reaction with palladium on charcoal as catalyst.

N-Acyl-a-amino acids are important compounds in both chemistry and biology. They are easily obtained in a transition metal-catalyzed, three-component domino reaction of an aldehyde, an amide, and CO. Whereas cobalt was mainly used for this process, Beller and coworkers [159] have recently shown that palladium has a... 

As described in the preceding sections, many domino reactions start with the formation of vinyl palladium species, these being formed by an oxidative addition of vinylic halides or triflates to Pd°. On the other hand, such an intermediate can also be obtained from the addition of a nucleophile to a divalent palladium-coordinated allene. Usually, some oxidant must be added to regenerate Pd11 from Pd° in order to achieve a catalytic cycle. Lu and coworkers [182] have used a protonolysis reaction of the formed carbon-palladium bond in the presence of excess halide ions to regenerate Pd2+ species. Thus, reaction of 6/1-386 and acrolein in the presence of Pd2+ and LiBr gave mainly 6/1-388. In some reactions 6/1-389 was formed as a side product (Scheme 6/1.98). 

Scheme 29. Synthesis of estradiol and cephalotaxine by two subsequent palladium-catalyzed domino reactions...

The transition metal-catalyzed domino reactions will undoubtedly have a splendid future which is underlined by the increasing number of publications in this area Steglich et al. presented an approach to arcyriacyanin A via a domino Heck reaction between a bromo(indolyl)maleiimide and 4-bromoindole.1811 The synthesis of 33 -bifurans by Ling et al. was achieved using a novel palladium-catalyzed domino dimerization and subsequent cyclization of acetylenic ketones.1821 Other applications of a combination of Heck reactions for domino processes are the syntheses of aza-heterocydes developed by our group.1831... 

Beyond the numerous applications of palladium in transition metal-catalyzed domino reactions there are a lot of other metals inducing domino processes. Ihara et al. found a strategy for the enan-tioselective synthesis of (+)-equilenin catalyzed by mangan and palladium complexes,1841 Whitby et al.1851 initiated domino cyclizations on a zirconocene template and furthermore Scherf et al. generated phenantrones by a nickel-mediated one-pot domino reaction.1861... 

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]. 

Scheme 58. Different modes of palladium-catalyzed domino reactions of bicyclopropylidene d)[148]...

The reactivity of the allenynol moiety itself under these cascade conditions was also explored [96]. Interestingly, treatment of allenynols 171a, 180, and 181 under the above palladium-catalyzed domino reaction conditions afforded the bridged medium-sized ring tricycles 182 as single isomers albeit in moderate yields (Scheme 63). Although complete conversion was observed by TLC and 1H NMR... 

A domino total synthesis of spirotryprostatin B (2) and three of its isomers has been published by Overman and Rosen, who apply two sequential palladium-catalyzed reactions (one-pot) to assemble the two spiro-fused rings [10] (Scheme 3). This work again makes it clear that complex heterocyclic systems may represent a harder challenge to synthetic... 

As for the biaryl ether containing macrocycles, an array of bioactive macrocycles with an endo aryl-aryl bond exist in nature. A new palladium catalyzed reaction has been recently developed in which bis(pinacolato)diborane(4) mediated the process to reach such a structural motif. The reaction consists of a domino process involving a Miyaura s arylboronic ester synthesis and an intramolecular Suzuki-coupling. Synthesis of a bicyclic A-B-O-C ring system of RP-66453 273, a neurotensine receptor antagonist, with an endo aryl-aryl and an endo aryl-aryl ether bond was described (Scheme 53).141... 

A recent paper explored the 1,2-functionalization of the allene moiety in monocyclic P-lactam allenynol derivatives under palladium-catalyzed reaction conditions <02CEJ1719>. Remarkably, a novel domino process, namely allene cyclization/intramolecular Heck reaction... 

Abstract Sequentially palladium-catalyzed reactions consist of combinations of identical, related, or significantly different palladium-catalyzed processes that occur in a sequential or consecutive fashion in the same reaction vessel without addition of further amounts of catalyst to the reaction media. This novel type of cascade reaction can be elaborated into both domino and multicomponent processes and represents a significant contribution to the highly topical field of diversity-oriented synthesis. 

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

This review is restricted only to sequences where initial and subsequent steps are catalyzed by palladium complexes. Furthermore, neither Pd-catalyzed unimolecular, parallel, nor multicomponent domino reactions will be treated in this overview. Reactions where identical functionalities are transformed by the same Pd-catalyzed step, i.e., multiple Pd-catalyzed reactions, will also not be covered. Hence, only those processes are within the scope of this review where an initially introduced Pd catalyst or precursor catalyzes related or significantly different reactions and where the sequence offers advantages over the stepwise conducted transformation. With respect... 

A three-component domino reaction catalyzed by palladium that produces 4,5-disubstituted dihydrobenzo[ ]furans from readily available starting materials has been developed by Pache and Lautens. The reactions of iodobenzenes of type 61 with Bui and tert- mx acrylate, as shown, give good yields of cyclization products (Scheme 96) <2003OL4827>. A reaction mechanism which involves sequential alkylation-alkenylation has been proposed. 

The catalytic generation of alkynones and chalcones by palladium catalyzed reactions is an entry to sequential, consecutive, and domino transformations and opens new routes to heterocycles by consecutive coupling-cyclocondensation or Cl-cyclocon-densation sequences. The advantages are not only the compatibility of similar reaction conditions but also the tunable reaction design that allows the combination of several organic and organometallic elementary reactions to new diversity oriented syntheses. Future developments will address also sequentially catalyzed processes... 

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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