Highly enantioselective organocatalytic trifluoromethyl carbinol synthesis--a caveat on reaction times and product isolation.
J Am Chem Soc
; 134(27): 11196-205, 2012 Jul 11.
Article
em En
| MEDLINE
| ID: mdl-22631871
ABSTRACT
Aldol reactions with trifluoroacetophenones as acceptors yield chiral α-aryl, α-trifluoromethyl tertiary alcohols, valuable intermediates in organic synthesis. Of the various organocatalysts examined, Singh's catalyst [(2S)-N-[(1S)-1-hydroxydiphenylmethyl-3-methylbutyl]-2-pyrrolidinecarboxamide] was found to efficiently promote this organocatalytic transformation in a highly enantioselective manner. Detailed reaction monitoring ((19)F-NMR, HPLC) showed that, up to full conversion, the catalytic transformation proceeds under kinetic control and affords up to 95% ee in a time-independent manner. At longer reaction times, the catalyst effects racemization. For the product aldols, even weak acids (such as ammonium chloride) or protic solvents, can induce racemization, too. Thus, acid-free workup, at carefully chosen reaction time, is crucial for the isolation of the aldols in high (and stable) enantiomeric purity. As evidenced by (19)F-NMR, X-ray structural analysis, and independent synthesis of a stable intramolecular variant, Singh's catalyst reversibly forms a catalytically inactive ("parasitic") intermediate, namely a N,O-hemiacetal with trifluoroacetophenones. X-ray crystallography also allowed the determination of the product aldols' absolute configuration (S).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetofenonas
/
Metanol
/
Aldeídos
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Hidrocarbonetos Fluorados
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article