Cyclic carbopalladation

Ring size Substrate Cyclic carbopalladation Cyclic acylpalladation... 

In 2010, Lian and Ma combined one molecule of 1,5-bisallene 381 with two molecules of 2,3-aUenoic acids 346 and developed an unexpected sandwich type of triple cyclization with excellent stereoselectivity. A possible mechanism involving sequential highly stereoselective anh-oxopalladation, intermolecular carbopalladation, cyclic... 

Stereochemical features in the oxidative addition and the elimination of /3-hydrogen of cyclic and acyclic alkenes are different. The insertion (palladation) is syn addition. The syn addition (carbopalladation) of R—Pd—X to an acyclic alkene is followed by the syn elimination of 3-hydrogen to give the trans-a ksne 6, because free rotation of 5 is possible with the acyclic alkene. On the other hand, no rotation of the intermediate 7 is possible with a cyclic alkene and the syn elimination of /3-hydrogen gives the allylic compound 8 rather than a substituted alkene. 

Termination of cyclic carbopalladation of alkynes via caibonylative lactamization can be achieved more satisfactorily with alkenyl or aryl halides containing an oo-caiboxamido or co-sulfonamido group than with those containing an 0)-amino group. The method appears to be satisfactory for the preparation of certain piperidines (e.g., 102) <96T(52)11529>. 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

Whereas the intermolecular Heck reaction is limited to unhindered alkenes, the intramolecular version permits the participation of even hindered substituted alkenes, and many cyclic compounds can be prepared by the intramolecular Heck reaction [37]. The stereospecific synthesis of an A ring synthon of la-hydroxyvitamin D has been carried out. Cyclization of the (7T)-alkene 88 gives the (fT)-exo-diene 90, and the (Z)-alkene 91 affords the (Z)-exo-diene 92 [38]. These reactions are stereospecific, and can be understood by cis carbopalladation to form 89 and the. sun-elimination mechanism. 

Oxypalladation of vinyl ether, followed by alkene insertion, is an interesting synthetic route to functionalized cyclic ethers. In prostaglandin synthesis, the oxypalladation of ethyl vinyl ether (40) with the protected cyclopentenediol 39 generates 41 and its intramolecular alkene insertion generates 42. The intermolecular insertion of the alkene 43, and /1-elimination of 44 occurred as one-pot reaction at room temperature, giving the final product 45 in 72% yield [46], The stereochemistry of the product shows that the alkene insertion (carbopalladation of 41) is syn. It should be noted that the elimination of /1-hydrogen from the intermediate 42 is not possible, because there is no /1-hydrogen syn coplanar to the Pd and, instead, the insertion of alkene 43 occurs. 

Bu3SnH (AIBN) fail, but the corresponding bromide or iodide does undergo hydro-stannation in moderate yield. Consequently, the cyclization of 1 to 2 is probably not a radical reaction but involves benzylpalladation. The paper includes several other examples of this cyclic carbopalladation such as the conversion of 3 to 4. 

Tandem cyclic carbopalladation cross-coupling process... 

Annelation. The Pd(0) complex in combination with N(C2H5)3 (1.5-2 equiv.) effects cyclic carbopalladation of substrates such as 1, a cyclohexene substituted by a y-iodoallyl electrophile group and activated by a carbonyl group,... 

Since both starting organometals and products in carbopalladation are organopalladium derivatives (Schemes 1 and 2), the process of carbopalladation can, in principle, repeat itself as exemplified in the reaction shown in Scheme 4. Thus, unless intercepted by some C - Pd bond cleaving process, this living process will stay alive, and no catalytic process will result. In both Heck and Maitlis reactions, the carbopalladation steps are spontaneously followed by /1-dehydropalladation and dechloropalladation, respectively. In cases where no such process occurs spontaneously, some processes must be deliberately devised usually through addition of appropriate reagents. In addition to dehydropalladation and dechloropalladation shown in Schemes 3 and 4 as well as in Eqs. 1 and 2 in Scheme 5, several other reactions used for this purpose are exemplied with prototypical cases of catalytic cyclic carbopalladation shown in Scheme 5 [9-19]. 

Patterns of cyclic carbopalladation. As discussed above, the fundamentally stoichiometric and living nature of carbopalladation imposes various difficulties to be overcome. Carbopalladation can, in principle, be either a single-stage process or double- or multiple-stage processes. Double-and multiple-stage carbopalladation reactions have often been called either domino or cascade carbopalladation reactions. In some cases, two-stage carbopalladation reactions have also been called tandem carbopalladation reactions. None of these three words is a chemical term, and choice between them is a matter of taste. In this chapter, the term cascade will be used for both double- and multiple-stage carbopalladation processes. 

As discussed in conjunction with the intermolecular cascade carbopalladation reaction shown in Scheme 4, it has been very difficult to satisfactorily control both queuing or pair -selectivity and regioselectivity of intermolecular cascade carbopalladation processes. Consequently, essentially all of the cascade carbopalladation reactions discussed here are at least partially intramolecular. The currently known cyclic cascade carbopalladation processes can be classified into a few to several types shown in Scheme 6. 

Cyclic acylpalladation. Another major subtopic of carbopalladation is acylpalladation. In the mid-1960s, two seemingly independent papers were published by J. Tsuji [24] and P.R. Hughes [25,26]. The former reported a perfectly alternating copolymerization of norbornadiene with CO (Scheme 8), while the latter described two related Pd-catalyzed carbonylation cyclizations shown in Scheme 9. 

The currently available data indicate that seven or eight discrete processes including Type I—III Ac-Pd reactions can take place under carbonylative conditions. In many cases, non-carbonylative cyclic carbopalladation has been observed even in the pressure of CO. A summary of all of these observed processes is presented in Scheme 13 as a guide map . 

In addition to a couple of reviews focused on results obtained in the authors group [38,39], a comprehensive book on organopalladium chemistry for organic synthesis [40] contains two dozens or so chapters on cyclic car-bopalladation and cyclic acylpalladation. Thus, its Part IV (pi 123-1659) on carbopalladation contains reviews of cyclic carbopalladation on the synthe-... 

Although this chapter focuses its attention on cyclic carbopalladation reactions other than the cyclic Heck reaction, it might be useful to discuss here the following variants of the cyclic Heck reaction. For the vast topic of the cyclic Heck reaction including those variants discussed below, the reader are referred to the following chapters of the Handbook of Organopalladium Chemistry for Organic Synthesis [40]. 

Cyclic Carbopalladation Terminated by Processes Other than /TDehydropalladation... 

The superior ability of alkynyltins to defer Pd-catalyzed alkynylation until after completion of the competing cyclic carbopalladation has been exploited in the synthesis of neocarzinostatin model compounds [85-87] (Scheme 28). 

The cyclic carbopalladation-cross-coupling tandem reaction has been extensively developed over the past several years. Despite earlier favorable findings with A1 and Zr [84], these metals are still scarcely used. On the other hand, organometals containing Sn and B have been widely used, and favorable results have been obtained for the formation of ffve-membered car-bocycles and heterocycles containing N and O from halodienes [88] (Eqs. 1 and 2 in Scheme 29), haloenynes [89-92] (Eqs. 3-5 in Scheme 29), haloaryl-alkynes [94,95] (Eqs. 6 and 7 in Scheme 29), and allenene derivatives [93,96] (Eqs. 8 and 9 in Scheme 29). 

Table 1 Effect of ring size ont he competition between cyclic carbopalladation and cyclic acylpalladation in the presence of CO...

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