Biomimetic Organocatalytic C–C-Bond Formations
75
Using the procedure above, several aldehydes and ketones could be
smoothly transformed to the fluorinated carbonyl compounds 67
(Scheme 16) (Enders and Hüttl 2005). It turned out that the aldehydes
were highly reactive forming the corresponding α-fluoroaldehydes after
3.5 h in good yields and by performing the fluorination at 0°C side reactions, such as homo aldol reaction, were suppressed. As expected the
ketones were less reactive, thus longer reaction times of up to 6 days
were necessary to give satisfying yields.
The enantiomeric excess of the (S)-proline-catalyzed α-fluorination
was generally found to be rather low. For example, the enantiomeric
excess of 70 was determined to be 29%. Because of the importance
of enantiopure organofluorine compounds we studied the efficiency of
several organocatalysts with respect of the asymmetric α-fluorination
of cyclohexanone as the model substrate and Selectfluor as the fluorinating agent (Scheme 16). Unfortunately, neither (S)-proline nor its
derivatives were able to catalyze the α-fluorination with high stereoselectivity. The highest enantiomeric excess was observed with trans-4hydroxy-(S)-proline (36% ee).
Although the highly enantioselective organocatalytic α-fluorination
of aldehydes was reported in 2005 independently by three different research groups (Marigo et al. 2005a; Steiner et al. 2005; Beeson and
MacMillan 2005) using NFSi as fluorinating agent and diarylprolinol
silylethers or imidazolidinone derivatives, respectively, the efficient
asymmetric amine-catalyzed α-fluorination of ketones still remains unsolved.
2.4
Asymmetric Organocatalytic Multicomponent
Domino Reactions
Efficient and elegant syntheses of complex organic molecules with multiple stereogenic centers continue to be important in both academic and
industrial laboratories (Nicolaou et al. 2003, 2006). In particular, catalytic asymmetric multicomponent domino reactions, used in the course
total syntheses of natural products and synthetic building blocks, are
highly desirable (Nicolaou et al. 2003, 2006; Tietze and Beifuss 1993;
Tietze 1996; Tietze and Haunert 2000; Wasilke et al. 2005; Ramón and
Yus 2005; Guo and Ma 2006; Pellissier 2006; Pellisier 2006; Tietze
75
Using the procedure above, several aldehydes and ketones could be
smoothly transformed to the fluorinated carbonyl compounds 67
(Scheme 16) (Enders and Hüttl 2005). It turned out that the aldehydes
were highly reactive forming the corresponding α-fluoroaldehydes after
3.5 h in good yields and by performing the fluorination at 0°C side reactions, such as homo aldol reaction, were suppressed. As expected the
ketones were less reactive, thus longer reaction times of up to 6 days
were necessary to give satisfying yields.
The enantiomeric excess of the (S)-proline-catalyzed α-fluorination
was generally found to be rather low. For example, the enantiomeric
excess of 70 was determined to be 29%. Because of the importance
of enantiopure organofluorine compounds we studied the efficiency of
several organocatalysts with respect of the asymmetric α-fluorination
of cyclohexanone as the model substrate and Selectfluor as the fluorinating agent (Scheme 16). Unfortunately, neither (S)-proline nor its
derivatives were able to catalyze the α-fluorination with high stereoselectivity. The highest enantiomeric excess was observed with trans-4hydroxy-(S)-proline (36% ee).
Although the highly enantioselective organocatalytic α-fluorination
of aldehydes was reported in 2005 independently by three different research groups (Marigo et al. 2005a; Steiner et al. 2005; Beeson and
MacMillan 2005) using NFSi as fluorinating agent and diarylprolinol
silylethers or imidazolidinone derivatives, respectively, the efficient
asymmetric amine-catalyzed α-fluorination of ketones still remains unsolved.
2.4
Asymmetric Organocatalytic Multicomponent
Domino Reactions
Efficient and elegant syntheses of complex organic molecules with multiple stereogenic centers continue to be important in both academic and
industrial laboratories (Nicolaou et al. 2003, 2006). In particular, catalytic asymmetric multicomponent domino reactions, used in the course
total syntheses of natural products and synthetic building blocks, are
highly desirable (Nicolaou et al. 2003, 2006; Tietze and Beifuss 1993;
Tietze 1996; Tietze and Haunert 2000; Wasilke et al. 2005; Ramón and
Yus 2005; Guo and Ma 2006; Pellissier 2006; Pellisier 2006; Tietze