Dehydropalladation

Intermolecular, enantioselective Heck reactions require a cyclic olefin as substrate, since syn carbopal-ladation of a cyclic olefin results in a geometrically defined a-alkyl-palladium compound. By necessity, the subsequent syn dehydropalladation must take place away from the newly formed chiral centre, thereby affording a chiral product. 

A different reaction mode was observed in the Pd-catalyzed co-cyclization of the 2-bromo-l-en-6-yne 76 and 4-octyne 77. After an intramolecular carbopalladation of the triple bond in 76, the formed alkenylpalladium bromide carbopalladates 77 and this is followed by another intramolecular carbopalladation or 67r-electrocyclization and dehydropalladation to yield the oligosubstituted indane derivative (Scheme 22). ... 

Tricyclic skeletons such as 85, 87, 89 with a central benzene ring are formed in the fully intramolecular Pd-catalyzed cascade cyclization of 2-bromo-l-ene-//,w-diynes 84, 86, 88 and analogs (Scheme 24). This process involves two alkyne relays in a row and a final 67r-electrocyclization or 6-endo-trig carbopalladation with ensuing / -dehydropalladation. 

Cascade carbopalladation sequences after attack on an alkene are most commonly terminated by dehydropallada-tion, if a / -hydride is available in a yy//-orientation. The intramolecular carbopalladation starting from the monocyclic diene 122 with a geminally disubstituted alkene terminator leads to a neopentylpalladium intermediate 123, which cannot undergo /J-dehydropalladation, but continue the cascade by a carbopalladation to eventually form the... 

Grigg and Xu have developed a variety of so-called queuing cascades involving allenes. The intra-intermolecular carbopalladation sequence of the <9-iodo-A-methyl-A -(methylallyl)aniline 142 and 1,1-dimethylallene 143 with subsequent / -dehydropalladation leads to the 1,3-dienyl-substituted indole derivative 144, which is immediately trapped by an added dienophile (e.g., A-methylmaleimide) in a Diels-Alder reaction to yield 145 (Scheme 37)7 ... 

All reactions described in this section are explained by (i) the oxidative addition of a halide to generate the arylpalladium halide 14 (ii) insertion of an alkene to form 15, which is regarded as carbopalladation of alkenes and (iii) formation of the new alkene 16 by elimination of /I-hydrogen (dehydropalladation). The reaction was reported independently by Mizoroki [3] and by Heck [4], and is called the Mizoroki Heck or Heck reaction [5]. 

When allylic compounds 346 are treated with Pd(0) catalyst in the absence of any nucleophile, 1,4-elimination (dehydropalladation) is a sole reaction path as shown by 347, and conjugated dienes are formed as a mixture of (E) and (Z) isomers [164,165], From terminal allylic compounds, terminal conjugated dienes are formed. 

Allylic amines are difficult to cleave, but they can be cleaved by using a cationic Pd complex and DPPB as a ligand. As an example, N, /V-dicthylgcranylamine (348) is converted 349, and its regioselective dehydropalladation affords the myrcene-type conjugated diene 350, and the reaction is applied to commercial production of the fragrant compound 351, called kovanol [166]. 1,4-Elimination of allylic amines is also possible as their amine salts using AcOH as a solvent [167],... 

Alkyl halides other than aryl and vinyl halides do not readily undergo oxidative addition with Pd and must, in general, first be converted to alkylmetals. In this connection, however, a recent report on the Ni catalysed selective alkyl-alkyl cross-coupling with Ni(acac)2 and Lil in THF represents a significant breakthrough.34 In cases where the alkyl group contains a p-H atom, reduction of the organic halide via p-dehydropalladation reductive elimination can be a serious side-reaction (Scheme 11.6). 

As p-hydride elimination is reversible, hydropalladation with the opposite regiochemistry provides a mechanism for forming regioisomers of the alkene. This allows the most stable alkene that is accessible by the hydropalladation-dehydropalladation sequence to dominate. The only restriction is that all of these processes are syn. The migration can be prevented by the addition of bases like silver carbonate, which effectively removes the hydrogen halide from the palladium complex as soon as it is formed. This synthesis of a complex trans dihydrofuran involves the Heck reaction followed by alkene isomerization and then a Heck reaction without migration to preserve the stereochemistry. 

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]. 

Kozhushkov SI, de Meijere A (2002) Carbopalladation of Alkenes not Accompanied by Dehydropalladation. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley, New York, p 1317... 

Currently, there seems to be a widespread tendency to call many reactions proceeding via carbopalladation the Heck reaction. However, this practice is clearly incorrect, since the scope of carbopalladation is significantly wider than that of the Heck reaction. The alkyne carbopalladation reaction shown in Scheme 4, which is not accompanied by -dehydropalladation may not be viewed as an example of the Heck reaction. In fact, this chapter focuses its attention on various carbopalladation reactions that may not be considered as examples of the Heck reaction. Although some of such processes are combined with the Heck reaction in many cases. 

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