Cascade reactions oxygen nucleophiles

Silyl allenes such as 48 and enol acetates such as 50 were particularly effective substrates for these reactions. The oxidative cascade reaction of trisubstituted alkene substrate 52 demonstrated a powerful application of ETIC chemistry to form bicycle 53 through consecutive carbon-carbon and carbon-oxygen bond construction. Highly diastereoselective reactions were observed when the nucleophile was... 

Oxygen nucleophiles have not frequently been used as terminators in cascade car-bometallation reactions. The intramolecular carbopalladation starting with an iodo- or trifluoromethylsulfonyloxyalkenyl-substituted derivative in the presence of tetrabutylam-monium acetate led to a suitable precursor of the sesquiterpene (-)-A (i )-capneUene. In this case, desymmetrization of the prochiral precursor was achieved using (5)-BINAP as the ligand on the palladium catalyst (Scheme 32). ... 

Hong and Overman reported the intramolecular termination of cascade reactions by oxygen nucleophiles in their studies on a novel synthesis of morphine (Scheme Starting from an iodophenol derivative tethered with an iodophenol silyl ether, intramolecular carbopalladation provided a bicycUc Tr-allylpalladium intermediate, which in turn was attacked by the oxygen functionality (Scheme 37). 

A mechanism for the piperazine-catalyzed formation of 4//-chromenes is complex cascade of reactions, starting with piperazine acting as a base which activates malononitrile, promoting Knoevenagel condensation, and also formation of an enamine, followed by Michael condensation, proton transfer, intermolecular cycliza-tion via a nucleophilic addition of the enolate oxygen to the nitrile group (hetero-Thorpe-Ziegler), and finally hydrolysis and tautomerization. 

There are hardly any examples for the use of sulfur nucleophiles in terminating cascade carbopalladation sequences, in contrast to oxygen and especially nitrogen nucleophiles. One reason for this might be found in the problems associated with the high degree of coordination of the palladium with the less oxidized sulfur nucleophiles such as thiols. However, arylsulfinates are excellent nucleophiles for cascade termination reactions, as has been shown by Grigg et al. (Scheme 34). ... 

Recently, Wang et al. [66] found that 2-methyUndoles was workable toward the ketenimine (Scheme 5.64). In this case, the alkyl group at the 2-position of indole ring increased the electron density of the 3-carbon and made the copper-catalyzed three-component reaction possible. The reaction was sensitive to oxygen. When the reaction was exposed to air, the oxidized products 99 were isolated. The cascade process is believed to involve a CuAAC, a nucleophilic addition, and a copper-catalyzed C—H bond activation-oxidation. 

---