Intermolecular reactions oxypalladation

A development of the last two decades is the use of Wacker activation for intramolecular attack of nucleophiles to alkenes in the synthesis of organic molecules [9], In most examples, the nucleophilic attack is intramolecular, as the rates of intermolecular reactions are very low. The reaction has been applied in a large variety of organic syntheses and is usually referred to as Wacker (type) activation of alkene (or alkynes). If oxygen is the nucleophile, it is called oxypalladation [10], Figure 15.4 shows an example. During these reactions the palladium catalyst is often also a good isomerisation catalyst, which leads to the formation of several isomers. 

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. 

Hosokawa, T., Murahashi, S.-l. Other intermolecular oxypalladation-dehydropalladation reactions. Handbook of Organopalladium... 

Allenols behaved similarly affording 5,6-dihydro-2H-pyrans 19 (Scheme 4). No expected product was found for the 3,4-allenols with R =R =R =H. Through control experiments with Ti-allylic Pd complexes it is believed that the reaction proceeded via the sequential intramolecular oxypalladation-intermolecular carbopalladation-p-dehalopalladation process (pathway 4, Scheme 1). 

In 1997, Hashmi et al. observed the Pd-catalyzed homodimerization of 1,2-allenyl ketones affording2-substituted4-(4 -oxo-2 -alken-2 -yl)furans (Scheme 31) [23]. The reaction may proceed via intramolecular oxypalladation involving the carbonyl oxygen, leading to the formation of furanylpalladium intermediate 69, followed by intermolecular carbopalladation with a second molecule of 1,2-allenyl ketone. Protonation of the C-Pd bond in 70 afforded the product 66 and regenerated Pd(II) (Scheme 32). 

Different regioselectivities were observed in the reaction of 3,4-pentadien-l-ols 387 with aryl iodides. The expected products 390 and 391 from the tt-allylpalladium intermediates 389 were not formed [151]. Exclusive formation of the dihydrofuran 388 is explained by concerted inter- and intramolecular exo-oxypalladation as shown by 392 to give 7r-allylpalladium 393, and reductive elimination gives rise to the dihydrofuran 394, showing that the intramolecular oxypalladation is faster than the intermolecular carbopalladation with Ar-Pd-I. 

The Wacker-type oxypalladation can take place both intermolecularly (Sect. V.3.1) and intramolecularly (Sect. V.3.2). The intermolecular Wacker oxidation of terminal alkenes provides the corresponding 2-ketones rather than aldehydes. This reaction has widely been used as a step in the syntheses of natural products and related compounds, as exemplified by Scheme 2 " and no attempts are made to thoroughly catalogue such examples here. 

Unlike the cases of alkenes, Wacker-type intermolecular oxypalladation reactions of alkynes have not been extensively investigated, although their intramolecular cyclization reactions have been developed into synthetically useful procedures (Sects. V3.2). In principle, they can proceed by a few alternative paths shown for the cases of terminal alkynes in Scheme 14. In reality, however, alkynyl C—H activation by Pd to give alkynylpalladium derivatives shown in Scheme 3 may well be the dominant path, as suggested by the carbonylative oxidation of terminal alkynes to give alkynoic acid esters shown in Scheme 15. Oxidative dimerization of alkynes is a potentially serious side reaction. Further systematic investigation of this fundamentally important process appears to be highly desirable. 

---