5
effects and steric hindrance of the substituent are important factors
determining the stereoselectivity for the product.
Acknowledgments
This work was supported by a Ministry of SMEs and Startups
[MSS-2019R10251604]. We thank Dr. Yeonsun Hong for
providing assistance.
2.3. Proposed reaction mechanism
The proposed reaction mechanism for the aldol reaction is
shown in Scheme 3.
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Scheme 3. Proposed reaction cycle.
As shown in Scheme 3, in our proposed reaction cycle,
cyclohexanone reacts with the primary amine to form an enamine,
which forms a transition structure (denoted A) to minimize steric
hindrance, and the aromatic aldehyde hydrogen bonds with the
ammonium salt and forms a new C-C bond via structure B while
minimizing the steric hindrance of the alkyl group. Finally, the
aldol products are formed by the hydrolysis of the iminium by the
H2O generated in the enamine formation and the H2O added in the
reaction. Water can help to form a product. However, the syn/anti
ratio and ee ratio were found to be good under the conditions of
DMF:H2O = 15:1.
3. Conclusion
Good reactivity and enantioselectivity were achieved in the
organic-catalyzed enantioselective reaction of cyclohexanone and
benzaldehyde using the mono-alkylated diamine derivative (R, R)-
(+)-1,2-diphenylethylenediamine (DPEN). Importantly, the used
catalysts could be recovered after the reaction. In addition, the
experimental results demonstrate that H2O is an essential
component of the catalytic cycle. By varying the substituents of
the aromatic aldehyde substrate, we found that the substituent has
a strong effect on the yield and stereoselectivity of the aldol
reaction. In addition, high stereoselectivity was obtained by
controlling the steric factors of the DPEN derivatives and the
hydrogen bonding between the ammonium salt and aromatic
aldehyde. It is expected that even better stereoselectivity could be
achieved by designing a new catalyst with larger substituents than
the phenyl group, as well as introducing other substituents to the
phenyl group.