Total Synthesis\nof (+)- and (−)-Calycanthidine\nand Formal Synthesis of (−)-Idiospermuline via Key Pd(0)-Catalyzed\nAsymmetric Allylations

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