M. Bilodeau. d.A. evans A Survey of Soft Enolization Techniques Chem 115 Formation of Glycine Enolate h、∠N、CO2Me co Me Elan, 1 equiv CO2R Kanemasa, Yoshioka J. Org. Chem. 1988 anemasa,Uchida, Wada. Org. Chem. 1990, CH2Cl, rt Co-Me LiBr, 1.5 equiv 1.2: 1 R=Me/R: Et3N, 1.2 equiv COmE Note: Regiochemistry of addition opposite to that above lequiv THF. rt Glycine Enolate CuCl. 5 mol% cN、CO2Me+RcHo EtN. 5 mol% Et2, Znl2, EtAICl employed in related reactions Ito tet. lett. 1985. 5781 869874) R= Me, 100% yield, 2: 1 trans/cis LiBr, 1.1 equiv R=Et2CH, 75% yield, trans only DBU, 1.0 equ When only EtN is employed -complex mixtures, low yields COmE THF. rt 77% yield, single isomer Ito, Sawamura, Hayashi J. Am. Chem. Soc., 1986, 108, 6405-6406. Grigg et al Tetrahedron198844557570;1989,4546494668 Tetrahedron lett.1989,30,4727-4730,1990,31,65696572 ,西 CO, Me [Au(c-HexNC)2) 'BF4/1(1 mol%) iPrCHO +CN OMe COmE Meo cH2Cl225°c ZnBr2, THF, 90% yield, 1: 2.7 99% yield, 98: 2 trans/cis AgOAc, THF, 90% yield, 1:>9 Related reactions have been conducted with MnBr2, MgBr2OEt, TINO3, CoCh the basis of Cu()'s strong preference for N coordination. Ago has recently been optimised to provide moderate-to-good enantioselectivity Hayashi, Ito et al. Tet Lett. 1991, 32, 2799-2802 22A-03 Ketone Acidity 11/1/01 3: 41 PMM. Bilodeau, D.A. Evans A Survey of 'Soft' Enolization Techniques Chem 115 77% yield, single isomer 1 equiv 1 equiv + LiBr, 1.1 equiv DBU, 1.0 equiv THF, rt NaI, MgBr2•OEt2, ZnI2, Et2AlCl employed in related reactions (Bull. Chem. Soc. Jpn. 1989, 62, 869-874). 82% yield AgOAc, THF, 90% yield, 1:>9 ZnBr2, THF, 90% yield, 1:2.7 Formation of Glycine Enolates. Tsuge, Kanemasa, Yoshioka J. Org. Chem. 1988, 53, 1384-1391. Kanemasa, Tatsukawa, Wada, Tsuge Chem. Lett. 1989, 1301-1304. Kanemasa, Uchida, Wada J. Org. Chem. 1990, 55, 4411-4417. LiBr, 1.5 equiv Et3N, 1.2 equiv THF, rt + + Grigg et al Tetrahedron 1988, 44, 557-570; 1989, 45, 4649-4668. Tetrahedron Lett. 1989, 30, 4727-4730; 1990, 31, 6569-6572. 1 equiv 1 equiv 1 equiv 2 equiv Ti(Oi-Pr)3Cl, 1.5 equiv Et3N, 1 equiv CH2Cl2, rt 80% yield 1.2:1 R=Me/R=i-Pr Note: Regiochemistry of addition opposite to that above. + + Lewis Acid Et3N Solvent rt LiBr, MeCN, 89% yield, 1:6 Related reactions have been conducted with MnBr2, MgBr2•OEt2, TlNO3, CoCl2 • Cu(I) catalyzes the reaction but with no enantioselectivity. This has been rationalized on the basis of Cu(I)'s strong preference for N coordination. • Ag(I) has recently been optimised to provide moderate-to-good enantioselectivity . Hayashi, Ito et. al. Tet. Lett. 1991, 32, 2799-2802. CH2Cl2, 25 °C [Au(c-HexNC)2]+BF4- / 1 (1 mol%) i-PrCHO + 1a : R=Et 1b : R=Me Ito, Sawamura, Hayashi J. Am. Chem. Soc., 1986, 108, 6405-6406. (R)-(S) Ito Tet. Lett. 1985, 5781. + RCHO CuCl, 5 mol% Et3N, 5 mol% THF, RT • When only Et3N is employed - complex mixtures, low yields R= Me, 100% yield, 2:1 trans/cis R=Et2CH, 75% yield, trans only 99% yield, 98:2 trans/cis 92% ee Glycine Enolates Ph N CO2Me CO2Me H Ph CO N 2Me MeO2C N O OMe O Li MeO Ph CO2Me N CO2Me Ph N CO2Me CO2Me Ph CO2R H N Ph Me CO2Me MeO2C MeO2C Ph CO2Me H N H Ph CO N 2Me CO2Me MeO2C CO2Me Me Me Me Me Me N Me t-Bu CO2Me CO2Me Me CO2Me t-Bu N CO2Me CN O Fe OMe O PPh2 N PPh2 NCH2CH2NR2 Me H Me i-Pr CO2Me CN CO2Me O N R CO2Me 22A-03 Ketone Acidity 11/1/01 3:41 PM