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 [Rh-2(S-TCPTAD)(4) (3 mol %), PhIO (1.6 equiv), MeOH (10 equiv) in PhCF3, 0 degrees 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).