Asymmetric α‐Hydroxylation of a Lactone with Vinylogous Pyridone by Using a Guanidine–Urea Bifunctional Organocatalyst: Catalytic Enantioselective Synthesis of a Key Intermediate for (20S)‐Camptothecin Analogues

Abstract We have developed a catalytic asymmetric synthesis of ( S )‐4‐ethyl‐6,6‐(ethylenedioxy)‐7,8‐dihydro‐4‐hydroxy‐1 H ‐pyrano[3,4‐ f ]indolizine‐3,10(4 H )dione ( 5 a ), a synthetic intermediate for (20 S )‐camptothecin analogues. A key step in this synthesis is an asymmetric α‐hydroxylation of a lactone with a vinylogous pyridone structure ( 8 a ) by using a guanidine–urea bifunctional organocatalyst. The present oxidation was successfully applied to the synthesis of C20‐modified derivatives of (+)‐C20‐desethylbenzylcamptothecin ( 13 ).