The Pd-catalyzed regio-and enantioselective ring opening of isoprene monoxide with primary amines as pronucleophiles is developed with good yield and enantioselectivity, constructing a quaternary stereocenter enantioselectively. This methodology was used as the chirality inducing key step in the asymmetric synthesis of vancosamine derivative 19. The synthesis was achieved in 9 total steps and 28.6% overall yield.Key words: palladium catalysis, enantioselectivity, quaternary stereocenter, asymmetric synthesis, amino sugar Palladium-catalyzed dynamic kinetic asymmetric transformation (DYKAT) on vinyl epoxide type substrates showcases the efficiency by which the ligands developed in these laboratories exercise control of the chemo-, regio-, and enantioselectivities in the asymmetric allylic alkylation (AAA) reactions. A series of nucleophiles, such as alcohols, 1 carbonates, 2 imides, 3 carbodiimides, 4 and stabilized carbon nucleophiles, 5 have been employed in the reaction. In the previous reported Pd-catalyzed ring opening of vinyl epoxides with nitrogen nucleophiles, 3 while the reaction between butadiene monoxide and phthalimide affords excellent yield and enantioselectivity, isoprene monoxide proved to be a more challenging substrate presumably because a quaternary stereocenter is generated in the reaction (Scheme 1). Envisioning that sterically less demanding primary amines might ameliorate some of the issues in such a case encouraged us to examine the use of benzylamines and other sterically less demanding nitrogen nucleophiles.
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