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Direct catalytic asymmetric Michael reaction of hydroxyketones: asymmetric Zn catalysis with a Et2Zn/linked-BINOL complex.
J Am Chem Soc. 2003 Mar 05; 125(9):2582-90.JA

Abstract

Full details of our direct Michael addition of unmodified ketones using new asymmetric zinc catalysis are described. Et(2)Zn/(S,S)-linked-BINOL complexes were successfully applied to direct 1,4-addition reactions of hydroxyketones. The first generation Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was effective for 1,4-addition of 2-hydroxy-2'-methoxyacetophenone (3). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et(2)Zn, we found that a 1,4-addition reaction of beta-unsubstituted enone proceeded smoothly at 4 degrees C to afford products in high yield (up to 90%) and enantiomeric excess (up to 95%). In the case of beta-substituted enones, however, the first generation Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was not at all effective. The second generation Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 with MS 3A system was developed and was effective for various beta-substituted enones to afford products in good dr, yield (up to 99%), and high enantiomeric excess (up to 99% ee). With the Et(2)Zn/1 = 4/1 systems, catalyst loading for beta-unsubstituted enone was reduced to as little as 0.01 mol % (substrate/chiral ligand = 10 000). The new system was also effective for 1,4-addition reactions of 2-hydroxy-2'-methoxypropiophenone (9) to afford chiral tert-alcohol in high enantiomeric excess (up to 96% ee). Mechanistic investigations as well as transformations of the Michael adducts into synthetically versatile intermediates are also described.

Authors+Show Affiliations

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12603146

Citation

Harada, Shinji, et al. "Direct Catalytic Asymmetric Michael Reaction of Hydroxyketones: Asymmetric Zn Catalysis With a Et2Zn/linked-BINOL Complex." Journal of the American Chemical Society, vol. 125, no. 9, 2003, pp. 2582-90.
Harada S, Kumagai N, Kinoshita T, et al. Direct catalytic asymmetric Michael reaction of hydroxyketones: asymmetric Zn catalysis with a Et2Zn/linked-BINOL complex. J Am Chem Soc. 2003;125(9):2582-90.
Harada, S., Kumagai, N., Kinoshita, T., Matsunaga, S., & Shibasaki, M. (2003). Direct catalytic asymmetric Michael reaction of hydroxyketones: asymmetric Zn catalysis with a Et2Zn/linked-BINOL complex. Journal of the American Chemical Society, 125(9), 2582-90.
Harada S, et al. Direct Catalytic Asymmetric Michael Reaction of Hydroxyketones: Asymmetric Zn Catalysis With a Et2Zn/linked-BINOL Complex. J Am Chem Soc. 2003 Mar 5;125(9):2582-90. PubMed PMID: 12603146.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Direct catalytic asymmetric Michael reaction of hydroxyketones: asymmetric Zn catalysis with a Et2Zn/linked-BINOL complex. AU - Harada,Shinji, AU - Kumagai,Naoya, AU - Kinoshita,Tomofumi, AU - Matsunaga,Shigeki, AU - Shibasaki,Masakatsu, PY - 2003/2/27/pubmed PY - 2003/2/27/medline PY - 2003/2/27/entrez SP - 2582 EP - 90 JF - Journal of the American Chemical Society JO - J Am Chem Soc VL - 125 IS - 9 N2 - Full details of our direct Michael addition of unmodified ketones using new asymmetric zinc catalysis are described. Et(2)Zn/(S,S)-linked-BINOL complexes were successfully applied to direct 1,4-addition reactions of hydroxyketones. The first generation Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was effective for 1,4-addition of 2-hydroxy-2'-methoxyacetophenone (3). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et(2)Zn, we found that a 1,4-addition reaction of beta-unsubstituted enone proceeded smoothly at 4 degrees C to afford products in high yield (up to 90%) and enantiomeric excess (up to 95%). In the case of beta-substituted enones, however, the first generation Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was not at all effective. The second generation Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 with MS 3A system was developed and was effective for various beta-substituted enones to afford products in good dr, yield (up to 99%), and high enantiomeric excess (up to 99% ee). With the Et(2)Zn/1 = 4/1 systems, catalyst loading for beta-unsubstituted enone was reduced to as little as 0.01 mol % (substrate/chiral ligand = 10 000). The new system was also effective for 1,4-addition reactions of 2-hydroxy-2'-methoxypropiophenone (9) to afford chiral tert-alcohol in high enantiomeric excess (up to 96% ee). Mechanistic investigations as well as transformations of the Michael adducts into synthetically versatile intermediates are also described. SN - 0002-7863 UR - https://www.unboundmedicine.com/medline/citation/12603146/Direct_catalytic_asymmetric_Michael_reaction_of_hydroxyketones:_asymmetric_Zn_catalysis_with_a_Et2Zn/linked_BINOL_complex_ L2 - https://doi.org/10.1021/ja028928+ DB - PRIME DP - Unbound Medicine ER -
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