M. Bilodeau. D.A. Evans A Survey of Soft Enolization Techniques Chem 115 Titanium enolates Reactions of titanium enolates Evans, Clark, Metternich, Novack, Sheppard J. Am. Chem. Soc. 1990, 112, 866. 人人 DIPEA I For Titanium: Enolization process not responsive to tertiary amine structure I DIPEA, Et3N, N-Ethylpiperidine all suitable bases 86%yied,>991 I DBU and tetramethylguanidine do not provide enolate I CH Cl2 is the only suitable solvent for these enolizations Reactions with Representative Electrophiles N-Propionyloxazolidone (1) Ethylisopropylketone Lewis Acid Enolization Lewis Acid Enolization i-PrOTiCl F-PrOTiCl3 99%,>99:1 80 CH2SP TiCI4'2THF 80 A-PrO)2TiCl 70 (A-PrO)3TICI 78%,98:2 PhSCH2Cl 93%,973 I Order of addition of reagents is important for TiCl4 R3N-TiCl4 Irreversible Complexation (CH2)2COEt H2C=CHCOEt CICH2NHCOPh I Order of addition of reagents is not important for i-PrOTiCk or(i-PrO)2TiCl R3N A-ProTiCl3 RaN-TICL(O/Pr) Reversible Complexation: 88%,>99: 1 89%,973 HC(OMe)3 MeOCH2NHCbz ■ Enolizable substrates CH(OMen Substrates Which present problems CH2OH 91%,964 ReAr. R<i-Pr 93%,99:1 J.Am.chem.Soc.190,112,82158216;Jog.Chem.1991,56,57505752 22A-07 Ketone Acidity 11/1/01 3: 42 PMM. Bilodeau, D.A. Evans A Survey of 'Soft' Enolization Techniques Chem 115 R=Ar, R<i-Pr ■ Substrates Which present problems: ■ Enolizable substrates: Titanium Enolates Irreversible Complexation + - R3N-TiCl TiCl4 4 R + 3N ■ Order of addition of reagents is important for TiCl4. ■ For Titanium: Enolization process not responsive to tertiary amine structure ■ DIPEA, Et3N, N-Ethylpiperidine all suitable bases . ■ DBU and tetramethylguanidine do not provide enolate. ■ CH2Cl2 is the only suitable solvent for these enolizations. ■ Order of addition of reagents is not important for i-PrOTiCl3 or (i-PrO)2TiCl2. R3N + i-PrOTiCl3 + - R3N-TiCl3(OiPr) Reversible Complexation TiCl4 R3N N-Propionyloxazolidone (1) Lewis Acid % Enolization TiCl4 i-PrOTiCl3 (i-PrO)2TiCl2 (i-PrO)3TiCl 100 100 70 ~10 TiCl4•2THF 80 Ethylisopropylketone Lewis Acid % Enolization TiCl4 i-PrOTiCl3 (i-PrO)2TiCl2 100 80 50 Reactions of Titanium Enolates 1. TiCl4 DIPEA 2. i-PrCHO Evans, Clark, Metternich, Novack, Sheppard J. Am. Chem. Soc. 1990, 112, 866. 86% yield, >99:1 99%, >99:1 BOMCl 93%, 97:3 PhSCH2Cl 89%, 97:3 ClCH2NHCOPh MeOCH2NHCbz 91%, 96:4 93%, 99:1 HC(OMe)3 99%, >99:1 88%, >99:1 78%, 98:2 H2C=CHCOEt H2C=CHCO2Me J. Am. Chem. Soc. 1990, 112, 8215-8216.; J. Org. Chem. 1991, 56, 5750-5752. 1 Reactions with Representative Electrophiles MeO OMe O R O Me PhS O t-Bu Me Me O MeO O Me O R Me O O Me N O Bn O O N Bn O Me O O Me N O Bn O Ti Cl Cl Cl Cl Ti Cln Bn O N O O Me O Me Me O O N O O Bn Me Me OH Me O Me N O Bn O Ti Cln Xp CH2OBn O Me Me O CH2SPh Xp Xp CH2NHCOPh O Me Me O CH2NHCBz Xp Xp CH2OH O Me O O O Me O CH(OMe)2 Xp Xp (CH2)2COEt O Me OMe O Me O Xp 22A-07 Ketone Acidity 11/1/01 3:42 PM