D A. Evans The Aldol reaction Imide Transformations Chem 206 Imide Hydrolysis Trans-esterification OMe Imides may suffer attack at either of the two C=O functions(eq 1, eq 2) OMe N3 TH(OBn4 RO OF-4949 Synthe sis) JACS1989, 111, 1063 Product distribution a function of attacking nucleophile(Tet. Lett. 1987, 28, 6141) Trans-thioesterification. Exo: Endo Substrate ubstrate Reagent Exo: Endo LOH06:89 9094% PhH2C LiOOH 96: 04 Damon, Tet. Lett.1990,31,28492852 OTIPS OTIPS OMe OTES OTES HF 25'C N3 BohN. X=SEt X=H OTBS 5% Pd/CaCO/Pbo (OF-4949 Synthesis)JACS 1989, 111, 1063 1993,115,44974513 RCOSR-RCHO Fukuyama, J Am. Chem. Soc 1990, 112, 7050-7051 Transamination to Weinreb Amides (see Handout 23A) Me Me(oMe)NHMe OMe o-Protect M. Bilodeau, unpublished results complete hydroytic selectivity possibl for recent examples see, J. Am. Chem. Soc 1992, 114, 9434-9453O N O O Bn R El O Bn N O Me O Me MeO N O Me O O Bn O N O OBn OMe O O NH NH2 O BocHN O N3 Bn O O LiO2H LiOH LiOOH LiOOH OR' O R El El R O N Bn O–C(O)OR' H N O PhH2C O O Me Bn Me O Me O MeO OH HN O O Bn N3 O BocHN O NH2 NH O O OMe O OBn OH LiOH LiOOH HN O O Bn RCOSR R Bn O N O Me OH O N H H H H H OTBS Et Me O O OTIPS OTES O O O Bn O O OMe N3 O OCMe3 N O Bn O RCHO Me3Al Me(OMe)NHMe N Me O O O Me Ph MeO OMe LiSEt Ti(OBn)4 OH N O Me OMe Me R X H H H H H OTBS Et Me O O OTIPS OTES O Bn-SLi O O OMe N3 O OCMe3 OBn MeO OMe O Me SBn R Me O R OP Et3SiH HOH/THF M. Bilodeau, unpublished results complete hydroytic selectivity possible for recent examples see, J. Am. Chem. Soc 1992, 114, 9434-9453 R–metal O-Protect THF, 0 °C 90-94% Damon, Tet. Lett. 1990, 31, 2849-2852 Trans-thioesterification: Trans-esterification (OF-4949 Synthesis) JACS 1989, 111, 1063 Transamination to Weinreb Amides (see Handout 23A) (OF-4949 Synthesis) JACS1989, 111, 1063 90-93% yield 89% yield Fukuyama, J. Am. Chem. Soc 1990, 112, 7050-7051 X = H X = SEt (Lepicidin Synthesis) J. Am. Chem. Soc 1993, 115, 4497-4513 97% THF, 25 °C 96% *5% Pd/CaCO3/PbO Substrate Reagent Exo:Endo Ratio 06 : 89 96 : 04 0 : 100 76 : 16 Exo:Endo Ratio Reagent Substrate Product distribution a function of attacking nucleophile (Tet. Lett. 1987, 28, 6141) pKa 20 Imides may suffer attack at either of the two C=O functions (eq 1, eq 2) endocyclic * * (2) (1) R'O– * exocyclic R'O– Imide Hydrolysis D. A. Evans The Aldol Reaction: Imide Transformations Chem 206