Assymetric Alkylation of Enolates

Assymetric Alkylation of Enolates - Myers Asymmet ric...

Info iconThis preview shows pages 1–4. Sign up to view the full content.

View Full Document Right Arrow Icon
HO C 6 H 5 NH 2 OH Et(C=NH 2 )OEt + Cl ; KO t -Bu, CH 3 I O N CH 3 C 6 H 5 CH 3 O N OH O CH 3 HO CH 3 O CH 2 CH 3 CH 3 HO CH 2 C 6 H 5 O NH OH N OH O CH 3 N OLi OLi CH 3 H N OH O CH 3 CH 2 C 6 H 5 O N CH 3 C 6 H 5 CH 3 O CH 2 CH 3 BnBr OO CH 3 OH CH 3 CH 3 CH 3 CH 3 CH 3 O O OH OH CH 3 CH 3 H H CH 3 CH 3 Ca IP h CH 3 OTDS CH 3 CH 3 PhSO 2 CH 3 CH 3 TDSO SO 2 Ph CH 3 CH 2 COCl Et 3 N NP h OH O CH 3 CH 3 HO Ph O CH 3 CH 3 NaOH Chem 2 15 Asymmetric Alkylation of Enolates Myers • An early milestone in the use of a chiral auxiliary for asymmetric alkylation: Meyers, A. I.; Knaus, G.; Kamata, K.; Ford, M. E. J. Am. Chem. Soc . 1976 , 98 , 567-576. LDA; EtI 3-6 N HCl 84% 78% ee 2-Oxazolines as carboxyl equivalents • Prolinol amide enolates provided an important advance: ( S )-2-Pyrrolidinemethanol Aldrich: $7.5/g (25 g) ( R )-2-Pyrrolidinemethanol Aldrich: $35.0/g (5 g) Evans, D.A.; Takacs, J.M.; Tetrahedron Lett . 1980 , 21 , 4233. Sonnet, P.; Heath, R. R. J. Org. Chem. 1980 , 45 , 3137. 2 LDA • 3° amides form Z -enolates selectively 1 N HCl, 75% yield, 76% de 92% yield, [ α ] D : –18.89 °, Lit. –25.4 ° Ionomycin Calcium Complex • Strongly nucleophilic prolinol amide enolates react with β -branched alkyl halides. proposal and application to iterative assembly of 1,3,n-substituted carbon chains by Evans et al. in synthesis of ionomycin: Evans, D. A.; Dow, R. L.; Shih, T. L.; Takacs, J. M.; Zahler, R. J. Am. Chem. Soc. 1990 , 112 , 5290-5313. KH, LDA; 83% dr 97 : 3 latent aldehyde aq. HCl, 100 °C; 91% 12 14 16 12 14 16
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Evans Oxazolidinone Auxiliaries in Asymmetric Synthesis: Alkylations NH O O CH 3 NH O O H 3 C CH 3 NH O O NH O O CH 3 NH O O N O O H 3 C CH 3 O CH 2 CH 3 NH O O NH O O As Originally Introduced, Two Enantio-complimentary Reagents: Acylation provides Imides , closer to esters than amides in terms of acidity, enolate nucleophilicity and cleavage chemistry. Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc. 1982 , 104 , 1737-1739. Now, several oxazolidinones are commercially available, in both enantiomeric forms: NH O O H 3 C CH 3 *1999 Aldrich Prices, can be dramatically lower from bulk suppliers. ( S )-(–)-4-Phenyl-2- oxazolidiinone 5 g $134 ( R )-(+)-4-Phenyl-2- oxazolidiinone 5 g $133 ( S )-(–)-4-Benzyl-2- oxazolidiinone 25 g $185 ( R )-(+)-4-Benzyl-2- oxazolidiinone 25 g $240 (4 S , 5 R )-(–)-4-Methyl-5-phenyl-2- oxazolidinone 5 g $156 ( S )-(–)-4-Isopropyl-2- oxazolidiinone 5 g $135 ( R )-(+)-4-Isopropyl-2- oxazolidiinone 2.5 g $102 (4 R , 5 S )-(+)-4-Methyl-5-phenyl-2- oxazolidinone 5 g $167 NH O O H 3 C CH 3 n -BuLi, THF, –78 °C; PrCOCl, 80-90% Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem. Soc. 1981 , 103 , 2127-2129. N O O H 3 C CH 3 O CH 2 CH 3 LDA, THF –78 °C Z -Enolates are formed with very high selectivity. Chelated geometry presumed in ground and transition states. BnBr, –78 °C 92% N O O H 3 C CH 3 O CH 2 CH 3 Bn >99 : 1 Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc. 1982 , 104 , 1737-1739 N O O CH 3 O CH 2 CH 3 LDA; BnBr 78% N O O CH 3 O CH 2 CH 3 Bn >99 : 1 N O O H 3 C CH 3 CH 2 CH 3 Li O
Background image of page 2
N O O CH 3 O CH 3 N O O CH 3 O CH 3 Et NaN(TMS) 2 , THF –78 °C; EtI 94 : 6 53% • Less reactive (non-allylic/benzylic) electrophiles require the use of sodium enolates or triflate as leaving group: Evans, D. A.; Ennis, M. D.; Mathre, D. J.
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 4
This is the end of the preview. Sign up to access the rest of the document.

Page1 / 8

Assymetric Alkylation of Enolates - Myers Asymmet ric...

This preview shows document pages 1 - 4. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online