Enantioselective synthesis of α-substituted ketones by asymmetric addition of chiral zinc enamides to 1-alkenes

Journal of the American Chemical Society

Volumn 125, Issue 21, 2003, Pages 6362-6363

  Nakamura, Masaharu ^a,b   Hatakeyama, Takuji ^b   Hara, Kenji ^c   Nakamura, Eiichi ^b  

^a JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^b UNIVERSITY OF TOKYO   (Japan)

^c HOKKAIDO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ALKENE DERIVATIVE; AMIDE; CYCLOHEXANONE; ENAMIDE; ETHYLENE; KETONE; PROPYLENE; STYRENE; UNCLASSIFIED DRUG; ZINC;

ADDITION REACTION; ALKYLATION; ARTICLE; CHIRALITY; ENANTIOSELECTIVITY; POLYMERIZATION; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0037500259     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja035091p     Document Type: Article

References (19)

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14. Racemization of the chiral center took place even under the best current hydrolysis conditions, which is not due to epimerization of the final ketone product but due to that of an imine intermediate.
15. 2 (2.06 g, 10.0 mmol), and ethyl 2-(bromomethyl)acrylate (2.42 mL, 20.0 mmol) were added at -78 °C. The reaction mixture was stirred at 0 °C for 6 h and then hydrolyzed with acetic acid buffer (20 mL). Purification by silica gel chromatography gave the desired α-alkylated ketone (2.15 g, 86% yield, 89.6% ee). The amino ether chiral auxiliary can be recovered in >70% yield.
16. Both isomers may be of nearly equal energies, but only the zinc enamide can take part in the addition reaction.
17. The reaction is general for 1-alkenes but produces a mixture of diastereomers as to the newly formed C-C bond. The stereochemical issue still remains to be resolved to make this extension synthetically useful.
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