Enantioselective intramolecular AZA-spiroannulation onto benzofurans using chiral rhodium catalysis

The development of efficient and enantioselective intramolecular aza-spiroannulation onto benzofurans using chiral rhodium catalysis is described. The optimized reaction conditions [Rh₂(S-TCPTAD) ₄ (3 mol %), PhIO (1.6 equiv), MeOH (10 equiv) in PhCF₃, 0°C] brought about oxidative aza-spiroannulation of 3-(carbamoylmethyl) benzofuran (3) resulting in (2R,3S)-2-methoxy-2H-spiro- [benzofuran-3,4′- oxazolidin]-2′-one (15a) in 69% yield with 86% ee, the absolute structure of which was determined by a combination of X-ray crystallography and vibrational circular dichroism (VCD) spectroscopy. The reaction is applicable to the asymmetric construction of various 2,3-dihydrobenzofuran derivatives bearing a nitrogen-containing tetrasubstituted carbon stereocenter at C3 (up to 92% ee).