Highly Efficient, Convergent, and Enantioselective Synthesis of Phthioceranic Acid

A new strategy for highly concise, convergent, and enantioselective access to polydeoxypropionates has been developed. ZACA‐Pd‐catalyzed vinylation was used to prepare smaller deoxypropionate fragments, and then two key sequential Cu‐catalyzed stereocontrolled sp3–sp3 cross‐coupling reactions allowed convergent assembly of smaller building blocks to build‐up long polydeoxypropionate chains with excellent stereoselectivity. We employed this strategy for the synthesis of phthioceranic acid, a key constituent of the cell‐wall lipid of Mycobacterium tuberculosis, in just 8 longest linear steps with full stereocontrol. A step‐economical synthesis of phthioceranic acid was achieved by using a conceptually new strategy. ZACA‐Pd‐catalyzed vinylation was used to prepare smaller deoxypropionate building blocks. Then two Cu‐catalyzed stereospecific sp3–sp3 cross‐couplings linked the smaller fragments together with full inversion of configuration to assemble large polydeoxypropionates in a stereoselective manner. ZACA=Zr‐catalyzed asymmetric carboalumination of alkenes.