Vicinal Difunctionalization of Alkenes and Allenes

Reactions that effect addition of two heteroatoms across an alkene are very powerful methods for the generation of heterocycles, and have significant potential synthetic utility. Several important advances in this area that involve the use of palladium catalysts have recently been reported [57]. Interestingly, many of these may involve high oxidation state Pd complexes as intermediates. 

Related aminohalogenation reactions of allenes, such as the conversion of 72 to 73, can be effected under similar reaction conditions (Eq. (1.32)) [59]. However, these 

A very interesting Pd atalyzed aminoacetoxylation reaction of alkenes was recently developed jointly by the Sorensen and Lee groups [60]. In a representative example, treatment of 75 with Pd(OAc)2 and PhI(OAc)2 provides oxazohdinone 76 in 65% yield with 20 1 dr (Eq. (1.33)). This transformation is heheved to proceed via a Pd /Pd catalytic cycle that is initiated by antLatninopaUadation of the alkene to afford 77. The intermediate Pd complex is then oxidized by PhI(OAc)2 to alkyl Pd intermediate 78, which undergoes C—O bond-forming reductive elimination to afford 76. 

Three different approaches to the synthesis of five-membered cyclic ureas have recently been described that involve Pd-catalyzed alkene diamination reactions. In a series of very interesting papers, Muniz has described the conversion of alkenes bearing pendant ureas to imidizolidin-2-one derivatives using catalytic amounts of Pd(OAc)2 in the presence of an oxidant such as PhI(OAc)2 or CuBr2 [61, 62]. For example, these conditions were used to effect the cyclization of 79 to 80 in 78% yield (Eq. (1.34)) [62aj. These reactions proceed via a mechanism similar to that shown above in Eq. (1.33), except that the heteropalladation may occur in a syn- rather than anti- fashion, and the reductive elimination occurs with intramolecular formation of a C—N bond rather than intermolecular formation of a C—O bond. The alkene diamination reactions have also been employed for the synthesis of bisindolines (Eq. (1.35)) [63] and bicyclic guanidines (Eq. (1-36)) [64]. 

The intermolecular diamination of 1,3-dienes with acyclic ureas to provide monocyclic or bicydic urea derivatives has been achieved by Uoyd-Jones and Booker-Milburn through use of a palladium catalyst combined with either benzo-quinone or O2 as an oxidant [65]. For example, diene 81 was converted to urea 82 in 82% yield (Eq. (1.37)). These transformations are mechanistically distinct from the reactions described above, and appear to involve intermediate jr-allylpalladium complexes. 

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