Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Feb 17;77(4):1722-37.
doi: 10.1021/jo202220x. Epub 2012 Feb 9.

Kinetic resolution of secondary alcohols using amidine-based catalysts

Ximin Li  1 , Hui Jiang, Eric W Uffman, Lei Guo, Yuhua Zhang, Xing Yang, Vladimir B Birman
Affiliations

Kinetic resolution of secondary alcohols using amidine-based catalysts

Ximin Li et al. J Org Chem. .

Abstract

Kinetic resolution of racemic alcohols has been traditionally achieved via enzymatic enantioselective esterification and ester hydrolysis. However, there has long been considerable interest in devising nonenzymatic alternative methods for this transformation. Amidine-based catalysts (ABCs), a new class of enantioselective acyl transfer catalysts developed in our group, have demonstrated, inter alia, high efficacy in the kinetic resolution of benzylic, allylic, and propargylic secondary alcohols and 2-substituted cycloalkanols, and thus provide a viable alternative to enzymes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Most successful amidine-based catalysts
Figure 2
Figure 2
Proposed transition state. Predictive model and geometry optimized by DFT calculations
Figure 3
Figure 3
Hydrogen bonding in 3-amino alcohols 29–31.
Figure 4
Figure 4
Rationale for the second-generation catalyst design
Figure 5
Figure 5
Transition state models of r the HBTM-catalyzed KR of alcohols 63 and 7.
Scheme 1
Scheme 1
Enzymatic Kinetic Resolution of Alcohols
Scheme 2
Scheme 2
Kinetic resolution of benzylic alcohols using CF3-PIP 1.
Scheme 3
Scheme 3
Deactivation of BTM 3 in the presence of moisture
Scheme 4
Scheme 4
Proposed mechanism of substrate inhibition of BTM.
See this image and copyright information in PMC

References

    1. For selected catalytic, enantioselective approaches to secondary alcohols, see: Hydride reduction of ketones: Cho BT. Chem Soc Rev. 2009;38:443.Cho BT. Tetrahedron. 2006;62:7621.Hydrogenation of ketones: Wang C, Wu X, Xiao J. Chem Asian J. 2008;3:1750.Sandoval CA, Ohkuma T, Muniz K, Noyori R. J Am Chem Soc. 2003;125:13490.Addition of carbon nucleophiles to aldehydes: Pu L, Yu HB. Chem Rev. 2001;101:757.Ring opening of epoxides: Jacobsen EN. Acc Chem Res. 2000;33:421.Pineschi M. Eur J Org Chem. 2006;22:4979.

    1. Kagan HB, Fiaud JC. Top Stereochem. 1988;18:249.
    1. Williams JMJ, Parker RJ, Neri C. Enzymatic kinetic resolution. In: Drauz K, Waldmann H, editors. Enzyme Catalysis in Organic Synthesis. 2. Vol. 1. New York, NY: Wiley-VCH; 2002. pp. 287–312.

    1. For reviews summarizing advances in this field, see: Vedejs E, Jure M. Angew Chem, Int Ed. 2005;44:3974.Denmark SE, Beutner GL. Angew Chem, Int Ed. 2008;47:1560.Spivey AC, Arseniyadis S. Top Curr Chem. 2010;291:233.Müller CE, Schreiner PR. Angew Chem, Int Ed. 2011;50:6012.Pellissier H. Adv Synth Catal. 2011;353:1613.

    1. For leading references to asymmetric catalyst designs that demonstrated competence in the KR of alcohols (s>10), see: 4-Aminopyridines: Fu GC. Acc Chem Res. 2004;37:542.Kawabata T, Yamamoto K, Momose Y, Yoshida H, Nagaoka Y, Fuji K. Chem Commun. 2001:2700.Spivey AC, Zhu F, Mitchell MB, Davey SG, Jarvest RL. J Org Chem. 2003;68:7379.Naraku G, Shimomoto N, Hanamoto T, Inanaga J. Enantiomer. 2000;5:135.Priem B, Pelotier B, Macdonald SJF, Anson MS, Campbell IB. J Org Chem. 2003;68:3844.Jeong KS, Kim SH, Park HJ, Chang KJ, Kim KS. Chem Lett. 2002:1114.Yamada S, Misono T, Iwai Y, Masumizu A, Akiyama Y. J Org Chem. 2006;71:6872.Ó Dálaigh C, Connon SJ. J Org Chem. 2007;72:7066.Crittall MR, Rzepa HS, Carbery DR. Org Lett. 2011;13:1250.Imidazoles: Miller SJ. Acc Chem Res. 2004;37:601.Ishihara K, Sakakura A, Hatano M. Synlett. 2007:686.Geng X-L, Wang J, Li G-X, Chen P, Tian S-F, Qu J. J Org Chem. 2008;73:8558.Hrdina R, Muller CE, Schreiner PR. Chem Commun. 2010;46:2689.Phosphines and phosphinites: Vedejs E, Daugulis O. J Am Chem Soc. 2003;125:4166.Mizuta S, Ohtsubo Y, Tsuzuki T, Fujimoto T, Yamamoto I. Tetrahedron Lett. 2006;47:8227.Vicinal diamines: Oriyama T, Taguchi H, Terakado D, Sano T. Chem Lett. 2002:26.N-Heterocyclic carbenes: Kano T, Sasaki K, Maruoka K. Org Lett. 2005;7:1347.Lewis acids: Mitsuda M, Tanaka T, Tanaka T, Demizu Y, Onomura O, Matsumura Y. Tetrahedron Lett. 2006;47:8073.Gissibl A, Finn MG, Reiser O. Org Lett. 2005;7:2325.Mazet C, Roseblade S, Köhler V, Pfaltz A. Org Lett. 2006;8:1879.

Publication types