D.A. Evans A Survey of Soft' Enolization Techniques Chem 206 Magnesium Enolates Titanium Enolates Rathke J. org. Chem. 1985,, 4877-4879 The Early Literature Syn. Comm1986,16,1133-1139 Lehnert, W. Tetrahedron lett. 1970. 4723-4724 Dieth MgCl2, 1 equiv EtN, 2 equiv OEt Et 85% yield Ketone Carboxylation gcl2, equiv Harrison, C R. Tetrahedron Lett. 1987, 28, 4135-4138 Nal, 2 equiv Et N, 4 equiv COOH TiCl4 cO, MeCN 7%y 30 min Ketone and aldehyde combined followed 91% yield MgCl2, 2 equiv by sequential addn of TiCl4 and then amine 95: 5 syn/anti EtoH -cO 2 CTICl4 Michael reaction CO2 Me COmE Et Brocchini. Eberle, Lawton J. Am. Chem. Soc. 1988. 110. 5211-5212 CH2Ch2,0° 73% yield, 93: 7 diastereomer ratio OH Et3N-H 10-15:1ZE Deuterium quench indicates 25% enolization of N-propionyloxazolidinoneO O EtO O OEt O O N Bn O Me O CO2Me O Me N O Bn O Mg Brn Et3N–H Me O Cl O O O Mg EtOH -CO2 MVK O COOH O Me N O Bn O CO2Me OEt O EtO O O Me O Me O O Me Ph TiCl4 NO2 O S OH O EtO OEt O Ph Me O Ph H O PhCHO Et Et O CHO Ph Me O Ph Ph O Me OH S O NO2 OH O Ph H TiCl4 O EtO OEt O Et Et + + + + The Early Literature 10-15:1 Z/E TiCl4 DIPEA THF -40° C Brocchini, Eberle, Lawton J. Am. Chem. Soc. 1988, 110, 5211-5212. 91% yield 95:5 syn/anti TiCl4 Et3N CH2Cl2, 0° C 30 min + Ketone and aldehyde combined followed by sequential addn of TiCl4 and then amine Harrison, C. R. Tetrahedron Lett. 1987, 28, 4135-4138. 75% yield TiCl4 Pyridine THF Lehnert, W. Tetrahedron Lett. 1970, 4723-4724. + Michael reaction Rathke Evans, Bilodeau unpublished results. 73% yield, 93:7 diastereomer ratio Magnesium Enolates Deuterium quench indicates 25% enolization of N-propionyloxazolidinone MgBr2•OEt2 Et3N CH2Cl2, 0° C 75% yield MgCl2, 2 equiv Et3N, 4 equiv +CO2 MeCN rt 70 % yield MgCl2, 2 equiv NaI, 2 equiv Et3N, 4 equiv Ketone Carboxylation 85% yield MgCl2, 1 equiv Et3N, 2 equiv MeCN, rt Diethylmalonate acylations J. Org. Chem. 1985, 50, 2622-2624. J. Org. Chem. 1985, 50, 4877-4879. Syn. Comm. 1986, 16, 1133-1139. D.A. Evans A Survey of 'Soft' Enolization Techniques Chem 206 Titanium Enolates CO2, MeCN rt