J. L Leighton, D. A. Evans Carbon Acylation with N-Methoxy-N-methylamides Chem 206 Acylating agents can be desiged where the tetrahedral intermediate exhibits exceptional stability (OMe)2 人人 THF/Et2O o-MeHgo OMe-110°cto0°C esen and c. Heathcock R凵 d or R-MgBr H3O Bn OMe THF,0°c M. Angelastro, N. Peet and P Be R= Me, n-Bu, or Ph; yields >90% Jorg.chem1989,54,3913 Weinreb Tet. Lett 1981. 22. 3815 Nucleophiles: Me R1-M RyMe-R制 H3O R1 R2 OMe Acceptable Unacceptable R-Li, R-Mgx R--Li(MgX) R-ZnX& other colalent metal alkyls Enolates and Metalloenamines J. Org. Chem.1991,56.2911-2 choli other colalent metal enolates THF,-78°c DIBAL LiAIH4 LiB(R)3H Weak hydride reagents: NaBH 47% In excellent review on all aspects of Weinreb amide chem THF.-78°ctoR.T M. Sibi, Organic Preparations and Procedures Int, 1993, 25(1), 15-40 J. Org. Chem.198954,4229 i Hydride Reductions Representative Organometals OMe OMe OMe TBSO OTBS OTBS N OMe DIBAl-H LOMe THF,7895% MeMgBr e OMe THF,0°C OMe OMe OMe TBsO Several other examples reported. Prasad and L Liebeskind Evans and s. mill g. Chem1993,58471 Me oMe MeMe Me H23-04 Weinreb Amides-1 11/5/008: 22 PMAcylating agents can be desiged where the tetrahedral intermediate exhibits exceptional stability: Chem 206 D. Evans and S. Miller J. Org. Chem. 1993, 58, 471. 95% THF, -78 °C DIBAl-H M. Angelastro, N. Peet and P. Bey J. Org. Chem. 1989, 54, 3913. THF, -78 °C 73% P. Thiesen and C. Heathcock J. Org. Chem. 1988, 53, 2374. THF/Et2O -110 °C to -80 °C 62% Several other examples reported. J. Prasad and L. Liebeskind Tetrahedron Lett. 1987, 28, 1857. THF, 0 °C 99% MeMgBr R-Li or R-MgBr THF, 0 °C R = Me, n-Bu, or Ph; yields > 90% J. L. Leighton, D. A. Evans Carbon Acylation with N-Methoxy￾N-methylamides Nu(-) H3O+ Weinreb Tet. Lett. 1981, 22, 3815. Nucleophiles: R–Li, R–MgX Acceptable DIBAL LiAlH4 LiB(R)3H Weak hydride reagents: NaBH4 Unacceptable R–ZnX & other colalent metal alkyls other colalent metal enolates An excellent review on all aspects of Weinreb amide chemistry: M. Sibi, Organic Preparations and Procedures Int., 1993, 25 (1), 15-40. Representative Organometals: H3O+ Hydride Reductions: R1–M H3O+ H3O+ R2–M W. Wipple, H. Reich J. Org. Chem. 1991, 56, 2911-2. THF, -78 °C THF, -78 °C to R. T. J. Org. Chem. 1989, 54, 4229. Enolates and Metalloenamines: 83% 47% R Li(MgX) RO OLi R' N O Me OMe LiN R Li Ar S O R' R O O CH2Li BrMg OEt N OMe O N MeO Me OLi R Me N OMe O N O Li Nu R N O Me OMe R Me Me R Nu O N O Me OTBS N O OMe Me Ar N O Me OTBS Me O O R1 Ar MeO2C N Me OR O OMe MeO2C P(OMe)2 OR O O Li P(OMe)2 O CbzHN N Me Bn O OMe CbzHN OEt Bn O Me N OMe Me OMe Me TBSO Me O2N OMe OMe Me O OMe OMe Me H OMe Me OMe Me TBSO Me O2N OMe OMe Me O OMe O t-Bu OLi O O t-Bu O R1 R2 O N O Me OMe OLi Me O O Me H23-04 Weinreb Amides-1 11/5/00 8:22 PM