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Ir/Cu Dual Catalysis: Enantio- and Diastereodivergent Access to α,α-Disubstituted α-Amino Acids Bearing Vicinal Stereocenters.
J Am Chem Soc. 2018 02 14; 140(6):2080-2084.JA

Abstract

We describe a fully stereodivergent synthesis of a range of α,α-disubstituted α-amino acids via an Ir/Cu-catalyzed α-allylation of readily available imine esters. The introduction of a Cu-Phox complex-activated imine ester into the chiral iridium-catalyzed allylic allylation process is crucial for its high reactivity and excellent enantio- and diastereoselectivity (up to >99% ee and >20:1 dr). Importantly, the two chiral catalysts allow for full control over the configuration of the stereocenters, affording all stereoisomers of the desired products. The utility of this methodology was demonstrated by synthesizing dipeptides and analogues of bioactive molecules in a stereodivergent manner.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Huo X
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering and ‡School of Pharmacy, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, P. R. China.
Zhang J
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering and ‡School of Pharmacy, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, P. R. China.
Fu J
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering and ‡School of Pharmacy, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, P. R. China.
He R
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering and ‡School of Pharmacy, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, P. R. China.
Zhang W
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering and ‡School of Pharmacy, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, P. R. China.

MeSH

Allyl CompoundsAmino AcidsCatalysisCopperDipeptidesEstersIminesIridiumStereoisomerism

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29381351

Citation

Huo, Xiaohong, et al. "Ir/Cu Dual Catalysis: Enantio- and Diastereodivergent Access to α,α-Disubstituted α-Amino Acids Bearing Vicinal Stereocenters." Journal of the American Chemical Society, vol. 140, no. 6, 2018, pp. 2080-2084.
Huo X, Zhang J, Fu J, et al. Ir/Cu Dual Catalysis: Enantio- and Diastereodivergent Access to α,α-Disubstituted α-Amino Acids Bearing Vicinal Stereocenters. J Am Chem Soc. 2018;140(6):2080-2084.
Huo, X., Zhang, J., Fu, J., He, R., & Zhang, W. (2018). Ir/Cu Dual Catalysis: Enantio- and Diastereodivergent Access to α,α-Disubstituted α-Amino Acids Bearing Vicinal Stereocenters. Journal of the American Chemical Society, 140(6), 2080-2084. https://doi.org/10.1021/jacs.8b00187
Huo X, et al. Ir/Cu Dual Catalysis: Enantio- and Diastereodivergent Access to α,α-Disubstituted α-Amino Acids Bearing Vicinal Stereocenters. J Am Chem Soc. 2018 02 14;140(6):2080-2084. PubMed PMID: 29381351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ir/Cu Dual Catalysis: Enantio- and Diastereodivergent Access to α,α-Disubstituted α-Amino Acids Bearing Vicinal Stereocenters. AU - Huo,Xiaohong, AU - Zhang,Jiacheng, AU - Fu,Jingke, AU - He,Rui, AU - Zhang,Wanbin, Y1 - 2018/02/02/ PY - 2018/1/31/pubmed PY - 2018/7/18/medline PY - 2018/1/31/entrez SP - 2080 EP - 2084 JF - Journal of the American Chemical Society JO - J Am Chem Soc VL - 140 IS - 6 N2 - We describe a fully stereodivergent synthesis of a range of α,α-disubstituted α-amino acids via an Ir/Cu-catalyzed α-allylation of readily available imine esters. The introduction of a Cu-Phox complex-activated imine ester into the chiral iridium-catalyzed allylic allylation process is crucial for its high reactivity and excellent enantio- and diastereoselectivity (up to >99% ee and >20:1 dr). Importantly, the two chiral catalysts allow for full control over the configuration of the stereocenters, affording all stereoisomers of the desired products. The utility of this methodology was demonstrated by synthesizing dipeptides and analogues of bioactive molecules in a stereodivergent manner. SN - 1520-5126 UR - https://www.unboundmedicine.com/medline/citation/29381351/Ir/Cu_Dual_Catalysis:_Enantio__and_Diastereodivergent_Access_to_αα_Disubstituted_α_Amino_Acids_Bearing_Vicinal_Stereocenters_ DB - PRIME DP - Unbound Medicine ER -