Enantioselective Synthesis of 2-Oxindole Spirofused Lactones and Lactams by Heck/Carbonylative Cylization Sequences: Method Development and Applications

An efficient one-pot assembly of all-carbon spiro-oxindole compounds from non-oxindole-based materials has been developed through a palladium-catalyzed asymmetric Heck/carbonylative lactonization and lactamization sequence. Diversified spirooxindole gamma-and delta-lactones/lactams were accessed in high yields with good to excellent enantioselectivities (up to 99% ee) under mild reaction conditions. The natural product coixspirolactam A was conveniently synthesized by applying the current methodology, and thus its absolute configuration was elucidated for the first time. Asymmetric synthesis of an effective CRTH2 receptor antagonist has also been demonstrated utilizing this method in the key step.