Palladium-Catalyzed trans-Hydroalkoxylation: Counterintuitive Use of an Aryl Iodide Additive to Promote C-H Bond Formation

We report an enantioselective palladium-catalyzed trans-hydroalkoxylation of propargylic amines with a trifluoroacetaldehydederived tether to build chiral oxazolidines. Diastereoselective hydrogenation using a heterogeneous palladium catalyst then gave access to protected benzylic amino alcohols in 45-87% yields and 84-94% ee values. Hydroalkoxylation of the alkynes required a catalytic amount of aryl iodide, highlighting the counterintuitive key role played by a putative Pd(II)/ArI oxidative addition complex to promote oxypalladation/protodemetalation.

Automated summary

In this study, we report an enantioselective palladium-catalyzed reaction, which utilizes a trifluoroacetaldehyde-derived tether to react with propargylic amines, generating chiral oxazolidines. Through diastereoselective hydrogenation using a heterogeneous palladium catalyst, protected benzylic amino alcohols can be obtained with yields of 45-87% and enantiomeric excess (ee) values of 84-94%. A catalytic amount of aryl iodide is required for the hydroalkoxylation of alkynes, highlighting the important role of a putative Pd(II)/ArI oxidative addition complex in promoting the oxypalladation/protodemetalation reaction.