Enantioselective Total Syntheses of (−)-FR901483 and (+)-8-<i>epi</i>-FR901483

The enantioselective total syntheses of the potent immunosuppressant FR901483 (<b>1</b>) and its 8-epimer (<b>47</b>) have been accomplished. Our approach features the use of building block <b>6</b> as the chiron, the application of the one-pot amide reductive bis-alkylation method to construct the chiral aza-quaternary center (dr = 9:1), regio- and diastereoselective intramolecular aldol reaction to build the bridged ring, and RCM to form the 3-pyrrolin-2-one ring

A Formal Enantioselective Total Synthesis of FR901483

A formal enantioselective total synthesis of the potent immunosuppressant FR901483 (<b>1</b>) has been accomplished. Our approach features the use of chiron <b>6</b> as the starting material, the application of the one-pot amide reductive bisalkylation method to construct the chiral aza-quaternary center (dr = 9:1), regio- and diastereoselective intramolecular aldol reaction to build the bridged ring, and ring closing metathesis to form the 3-pyrrolin-2-one ring

A General Method for the One-Pot Reductive Functionalization of Secondary Amides

A one-pot reaction for the transformation of common secondary amides into amines with C–C bond formation is described. This method consists of <i>in situ</i> amide activation with Tf₂O–partial reduction–addition of <i>C</i>-nucleophiles. The method is general in scope, which allows employing both hard nucleophiles (RMgX, RLi) and soft nucleophiles, as well as enolates. With the use of soft nucleophiles, the reaction proceeded with high chemoselectivity at a secondary amide in the presence of ester, cyano, nitro, and tertiary amide groups