D A. Evans Carbonyl Addition Reactions: Chelate Organization Chem 206 Chelate organization provides a powerful control element in carbonyl addition reactions Lets begin with a case where chelation is precluded:(Path A) Nu-M BuanF-PhiMe in the ahn-Eisenstein model iN >99:1 T Hiyama& Co-workers, J.Am.Chem.Soc.1984,106.4629 X=OAC X= OCOPh 96 Reviews Reetz, Accts. Chem. Res. 1993, 26, 462-468(pdf) Reetz, Angew. Chem. Int. Ed. 1984, 23, 556-569 PhMe2SH-H Lets begin with the hydride reductions of alkoxy ketones H-bonding Chelate Model path A Substituent (X) Ratio X= NHCO,Et <1: 99 J Am. chem.196.421×:0cph7:93 R RL LiAIH4 10°C H: Chelation model Ratio Model R=CH,OBn THF 30:70 Tet Lett. 1982, 23, 2355 R=CH2OBnE202:98Chelate path C R=SiPh2(t)Bu THF 95: 5 Cram: RL=OR Degree of chelate organization may be regulated by choice of solvent and protecting group. Note that SiPh2 (t)Bu group prevents chelation for most Lewis acids. There are dramatic exceptions However: Carbonyl Additon: Chelate Control: Evans JACS 2001, ASAP(handout)R R O O R M R O O R R M R L R OR O H: RO H C O M O R R R C O O O M R R R Nu O C R O M O R R R Nu OR R L R L H R L H H: H: H + H + Nu R OH O R R Nu R R O OH R OH OR R R L R L R OR OH OH OR R R L Me O Me OR Me Ph Me O X X O Me Ph Bu4N + F￾LiAlH4 PhMe2Si–H PhMe2Si–H (OR) THF THF Et2O X OH Me Ph OR OH Me R Ph Me OH X R Me OH OR Ph Me OH X X OH Me Ph Degree of chelate organization may be regulated by choice of solvent and protecting group. Note that SiPh2(t)Bu group prevents chelation for most Lewis acids. There are dramatic exceptions However: 2 : 98 -10 °C Overman Tet Lett. 1982, 23, 2355 Chelate Ratio 30 : 70 Solv. R = CH2OBn R = CH2OBn R = SiPh2 (t)Bu Model 95 : 5 Chelate Cram: RL=OR X = OCOPh <1 : 99 Ratio H-bonding Chelate Model T. Hiyama & Co-workers, J. Am. Chem. Soc. 1984, 106, 4629. TFA, 0 °C Substituent (X) 7 : 93 X = NHCO2Et Lets begin with a case where chelation is precluded: (Path A) ‡ path C path B path A ‡ Lets begin with the hydride reductions of alkoxy ketones X = OCOPh 96 : 4 X = OAc 95 : 5 X = NMe2 Substituent (X) T. Hiyama & Co-workers, J. Am. Chem. Soc. 1984, 106, 4629. Let RL = X in the Ahn-Eisenstein model Ratio >99 : 1 Nu–M Reviews Reetz, Angew. Chem. Int. Ed. 1984, 23, 556-569 Reetz, Accts. Chem. Res. 1993, 26, 462-468 (pdf) ‡ Nu–M Chelate organization provides a powerful control element in carbonyl addition reactions D. A. Evans Carbonyl Addition Reactions: Chelate Organization Chem 206 Chelation model Carbonyl Additon: Chelate Control: Evans JACS 2001, ASAP (handout)