D.A. Evans Enolate Alkylation: Chiral Imide Enolates Chem 206 灿xpe0- Enolate amination TrisVl-N ACS1987,109,6881 HOAC JACs1990,112,40124030 or NaNTM diastereoselection 91-99+% enolization selectivity >100:1 M=Lil BocN=NBoc JAcS1986,108,3695 CHMe 2 Tet1988,44,552540 Alkyl Halide BocHNNBoc 50-120 O-2N3 selection 97-99*% M=Li,THF≤0°C CH2C=CHCH2 Br (Trisyl-N3) CHMe2 M=Na,TH-78to0°C 50:1 CH3I 13:1Enolate Hydroxylation Enolate Acylation JAcS.1982.104.1737 00 00 PhHC—NSO2F Na-N(TMS 0JAcs1984106.1154 Imide( r) RatioYield Diastereoselection -97:3 Na enolate is required PhCH2- 94:686% CH2=CHCH 95 91% MeO2 CCH2 CH2 CH2 96:468% 90:1077% New stereocenter not lost 194% through enolization JACS X-ray structure For all indicated rxns, as the R on the enolate grp increases in size enolate-El face selectivity increases. ExplainMe N O O O Me2CH R1 R2 R O N O O M O O N O R Me Ph Me2CH R O N O O M N O O O Me2CH Et Me O CH3I CH3CH2I ArCH2Br ArCH2OCH2Br CH2C=CHCH2Br R XC O El El O XC R SO2N3 CHMe2 CHMe2 Me2HC R N O O O Me Ph N O R O O Bn M BocN=NBoc O PhHC NSO2Ph N O R O O Bn BocHNNBoc N3 Bn O O R N O R Cl O Me3C￾MeO2CCH2CH2CH2- PhCH2- Na-N(TMS)2 CH2=CHCH2- Li–NR2 Me Ph O N O O R OH For all indicated rxns, as the R on the enolate grp increases in size enolate-El face selectivity increases. Explain. D. A. Evans Enolate Alkylation: Chiral Imide Enolates Chem 206 El(+) Alkyl Halide 50-120 : 1 Ratio 50 : 1 50 : 1 25 : 1 13 : 1 M = Li, THF < 0 °C M = Na, THF -78 to 0 °C JACS. 1982,104, 1737. El(+) LDA or NaNTMS2 enolization selectivity >100:1 Alkali Metal enolates: marginal reaction Enolate Hydroxylation 94 : 6 Enolate Amination Yield Imide (R) Ratio * Ph￾JACS. 1985,107, 4346. 86 % 91 % 68 % 77 % 94 % 95 : 5 96 : 4 90 : 10 >99 : 1 Na enolate is required. Why? Trisyl-N3 JACS 1987,109, 6881. HOAc diastereoselection 91-99+ % diastereoselection 97-99+ % JACS 1986,108, 3695. M = K M = Li JACS 1990,112, 4012-4030 (Trisyl-N3 ) Tet. 1988, 44, 5525-40 Diastereoselection ~ 97 : 3 JACS 1984, 106, 1154. Enolate Acylation New stereocenter not lost through enolization authentic X-ray structure