D. A. Evans Introduction to Complex Aldol Bond Constructions Chem 206 Bafilomycin A, Synthesis: An example of polypropionate assembage Evans. Calter. Tetrahedron Lett. 1993. 34. 6871 Enolization Conditions: PhBCl2, APT NEt, CH2Cl, -78C MeMe oMe Critical Aldol Disconnection diastereoselection Me. >99:1 Critical Aldol Disconnection OMe Me TMSOI Aldehyde Fragment: Target contains syn aldol retro with anti-Felkin relationship at 1&2 Enolate Fragment: Can the needed enolate facial bias be built into the reaction?? diastereoselection >95 Aldol Model Studies Enolization Conditions: PhBCl2, A-Pr2NEt, CH2Ch, -78oC MeMe oMe OTBSOTES O OTBSOTES tBu tBu Me2 CHCHO TMSOII The Critical observation Me2 CHCHO le diastereoselection Bafilomycin AlBafilomycin A1 Me O Me O Me O Si tBu tBu Me Me O Me O Me O Si tBu tBu Me O O Me OMe Me OMe Me TMSO Me OH Me Me Me O Me O Me O Si tBu tBu Si tBu tBu O O Me O Me Me Me OH Me Me Me TBSO O O Me OMe Me OMe Me HO Me OH OH Me OH Me Me Me Me O O O Me OMe Me OMe Me TMSO Me H O Me Me Me H TBSO Me O Me Me O Me O Me O Si tBu tBu O OTBS Me OTES Me Me Me Me Me OR Me OR Me O O O Me OMe Me OMe Me HO Me OR OH Me OH Me Me Me Me O Me2CHCHO Me2CHCHO O O Me OMe Me OMe Me RO Me H O Me O O Me O Me Me Si tBu Me Me OH Me tBu O OTBS Me OTES Me Me Me Me OH Me D. A. Evans Introduction to Complex Aldol Bond Constructions Chem 206 Bafilomycin A1 Synthesis: An example of polypropionate assembage Critical Aldol Disconnection Enolization Conditions: PhBCl2 , i-Pr2NEt, CH2Cl2 , -78oC. diastereoselection >99:1 diastereoselection 62:38 9 diastereoselection >99:1 Aldol Model Studies The Critical Observation Enolization Conditions: PhBCl2 , i-Pr2NEt, CH2Cl2 , -78oC. diastereoselection >95:5 60% Critical Aldol Disconnection Required: Syn aldol addition Aldehyde Fragment: Target contains syn aldol retron wilth anti-Felkin relationship at 1 & 2 Enolate Fragment: Can the needed enolate facial bias be built into the reaction?? 1 2 Evans, Calter, Tetrahedron Lett. 1993, 34, 6871 94% Bafilomycin A1 HF.pyridine, THF, 25oC