Total Synthesis of (+)- and (-)-Calycanthidine and Formal Synthesis of (-)-Idiospermuline via Key Pd(0)-Catalyzed...

We envisioned a novel asymmetric strategy to access unsymmetrically substituted dimeric 2-oxindoles [(S,S)-8 and (R,R)-8] for the total synthesis of calycanthidine (4a). The key to success is the development of efficient Pd(0)-catalyzed asymmetric sequential allylations [via a highly enantioselective [up to 94% enantiomeric excess (ee)] and diastereoselective (up to ∼13:1) process] of unsymmetrically protected dimeric 2-oxindoles at the 3,3' position [such as (S,S)-8 and (R,R)-8]. Gratifyingly, a mixture of bis-ester (±)-10a, ester-carbonates (±)-10b and (±)-10c, and bis-carbonate 10d could afford (S,S)-8 and (R,R)-8 in highly stereoselective fashion, thereby culminating in the total synthesis of (+)-calycanthidine [ent-(4a)] and (-)-calycanthidine (4a). This effort also culminated in the formal total synthesis of idiospermuline (5).