Synlett 2017; 28(11): 1278-1281
DOI: 10.1055/s-0036-1588852
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© Georg Thieme Verlag Stuttgart · New York

Kinetic Resolution of 5-Substituted Oxazinones with Bifunctional Chiral Base/Squaramide Organocatalysts

Serap Eröksüz
Cologne University, Department of Chemistry, Organic Chemistry, Greinstraße 4, 50939 Cologne, Germany   Email: berkessel@uni-koeln.de
,
Jörg M. Neudörfl
Cologne University, Department of Chemistry, Organic Chemistry, Greinstraße 4, 50939 Cologne, Germany   Email: berkessel@uni-koeln.de
,
Cologne University, Department of Chemistry, Organic Chemistry, Greinstraße 4, 50939 Cologne, Germany   Email: berkessel@uni-koeln.de
› Author Affiliations
Further Information

Publication History

Received: 01 March 2017

Accepted after revision: 09 May 2017

Publication Date:
31 May 2017 (online)


Abstract

5-Substituted oxazinones provide N-protected β2-amino acid esters upon alcoholytic ring opening. Thus far, this access to enantiopure β2-amino acids has been restricted to the use of enzymes (hydrolases) as catalysts for the kinetic resolution of racemic 5-substituted oxazinones, and branched alkyl or ortho-substituted aryl groups on the substrate oxazinone’s 5-position were typically not tolerated. We herein report that certain bifunctional chiral base/squaramide organocatalysts, in particular those derived from cis-1,2-diaminocyclohexane or 9-amino-9-epi-quinine, allow the first organocatalytic kinetic resolution of this ‘difficult’ class of oxazinone substrates, affording N-protected β2-amino acid esters with selectivity factors up to 43.

Supporting Information

 
  • References and Notes

    • 1a Berkessel A. Cleemann F. Mukherjee S. Müller TN. Lex J. Angew. Chem. 2005; 117: 817 ; Angew. Chem. Int. Ed. 2005, 44, 807
    • 1b Berkessel A. Mukherjee S. Cleemann F. Müller TN. Lex J. Chem. Commun. 2005; 1898
    • 1c Berkessel A. Mukherjee S. Müller TN. Cleemann F. Roland K. Brandenburg M. Neudörfl JM. Lex J. Org. Biomol. Chem. 2006; 4: 4319
    • 1d Berkessel A. Cleemann F. Mukherjee S. Angew. Chem. 2005; 117: 7632 ; Angew. Chem. Int. Ed. 2005, 44, 7466
    • 1e Renzi P. Kronig C. Carlone A. Eröksüz S. Berkessel A. Bella M. Chem. Eur. J. 2014; 20: 11768
    • 2a Okino T. Hoashi Y. Takemoto Y. J. Am. Chem. Soc. 2003; 125: 12672
    • 2b Okino T. Nakamura S. Furukawa T. Takemoto Y. Org. Lett. 2004; 6: 625
    • 2c Okino T. Hoashi Y. Furukawa T. Xu X. Takemoto Y. J. Am. Chem. Soc. 2005; 127: 119
    • 2d Berkessel A. Seelig B. Synthesis 2009; 2113
  • 3 Berkessel A. Jurkiewicz I. Mohan R. ChemCatChem 2011; 3: 319
  • 4 For an enzymatic (dynamic) kinetic resolution of β-lactams, affording enantiopure N-Cbz-protected β2-amino acid esters, see: Gianolio E. Mohan R. Berkessel A. Adv. Synth. Catal. 2016; 358: 30
  • 6 Berkessel A. Ong MC. Nachi M. Neudörfl JM. ChemCatChem 2010; 2: 1215
    • 7a Zhu Y. Malerich JP. Rawal VK. Angew. Chem. 2010; 122: 157 ; Angew. Chem. Int. Ed. 2010, 49, 153
    • 7b Konishi H. Lam TY. Malerich JP. Rawal VH. Org. Lett. 2010; 12: 2028
  • 8 Lee JW. Ryu TH. Oh JS. Bae HY. Jang HB. Song CE. Chem. Commun. 2009; 7224
  • 9 CCDC 874934 and CCDC 874935 contain the supplementary crystallographic data for compounds II·HCl and IV, respectively. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 10 The preparation of the catalysts and substrates used is described in the Supporting Information. Analytical data of cis-DACH derived squaramide catalyst II, 3-[3,5-bis(trifluoromethyl)anilino]-4-([(1R,2S)-2-(piperidin-1-yl)cyclohexyl]-amino)cyclobut-3-ene-1,2-dione: Pale yellow solid; mp 157–159 °C. 1H NMR (300 MHz, CD3OD): δ = 1.49–1.55 (m, 12 H), 1.62–1.99 (m, 3 H), 2.93 (br s, 5 H), 7.52 (s, 1 H), 8.14 (s, 2 H). 13C NMR (75 MHz, CD3OD): δ = 18.76, 22.88, 23.14, 24.64, 28.03, 31.80, 50.63, 50.92, 65.24, 115.05, 115.10, 123.22 (q, J = 270.3 Hz), 132.47 (q, J = 32.9 Hz), 141.17, 163.80, 169.63, 181.02, 184.10. FT-IR (ATR): 2937 (w), 1791 (w), 1685 (w), 1598 (m), 1544 (m), 14733 (m), 1436 (m), 1375 (s), 1330 (m), 1274 (s), 1244 (w), 1174 (s), 1124 (s), 933 (m), 877 (m), 731 (m) cm–1. MS (ESI): m/z [M + H]+ = 490.1. HRMS (ESI): m/z [M + H]+ calcd for C23H25F6N3O2: 490.1929; found: 490.193. [α]589 –7.9, [α]546 –6.7 (c = 0.5 in MeOH, at 20 °C).
  • 11 Kinetic resolutions: The reaction was carried out in abs. toluene at room temperature and under an inert atmosphere. The oxazinone (75.0 mmol, 1.0 equiv) and allyl alcohol (5.1 μL, 1.0 equiv) were dissolved in abs. toluene (1.0 mL), and 5.0 mol% of the catalyst were added. Conversions/yields and enantiomeric excesses (ee) were determined by HPLC on chiral stationary phase as described in the Supporting Information.