Abstract
Both steric repulsion and electronic effect govern the stereoselectivity in asymmetric catalysis. Rationally electronic-tuned N -(2-hydroxylphenyl)-(S)-prolinamide derived catalysts were designed, synthesized, and evaluated in the asymmetric aldol reaction. The results indicate that the enantiomeric ratios of products correlate well with the Hammett constants, which confirms that the enantioselectivity was improved via rationally tuning catalyst electronic effects.
Highlights
Factors governing stereoselectivity in asymmetric catalysis are important issues in organic chemistry
A more acidic catalyst would be a better hydrogen-bond donor, and produce higher stereoselectivity via a tighter transition state. This idea was proved by Gong, suggesting that catalysts with electron-withdrawing groups show higher enantioselectivity than those with electron-donationg groups in the N-aryl and N-(2-hydroxylethyl)-(S)-prolinamide derivativescatalyzed aldol reaction of p-nitrobenzaldehyde and acetone.[22,23]
After investigating rational electronic tuning of catalysts to improve enantioselectivity in the asymmetric borane reduction of ketones,[21,24,28] we wished to study the correlation between the enantiomeric ratio of product and the Hammett constant of the catalyst substituent in the asymmetric aldol reaction system, to understand the electronic tuning by using the designed catalysts with very similar structural feature to completely exclude steric difference
Summary
Factors governing stereoselectivity in asymmetric catalysis are important issues in organic chemistry. N-(2-Hydroxylphenyl)-(S)-prolinamide was shown to catalyze the asymmetric aldol reaction with low enantioselectivity.[46] It possesses two hydrogen-bond donors (an amide H and a phenolic hydroxy H) and should catalyze the asymmetric aldol reaction via a favorable transition state (TS4, Scheme 1), similar to that in the N-(2-hydroxylethyl)-(S)-prolinamide derivatives-catalyzed reaction suggested by Gong, et al.[23] To study the enantioselective improvement via rationally tuning the electronic effect of catalysts we designed a series of catalysts 1a-d.
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