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Synlett 2020; 31(20): 2018-2022
DOI: 10.1055/s-0040-1707303
letter

Kinetic Resolution of α-Nitrolactones by Catalytic Asymmetric Hydrolysis or Ester–Amide Exchange Reaction

Ryota Nakao
a   Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan   Email: sakakura@okayama-u.ac.jp
,
Yudai Fujii
a   Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan   Email: sakakura@okayama-u.ac.jp
,
Ichiro Hayakawa
b   Graduate School of Integrated Basic Sciences, Nihon University, 3-25-40 Sakurajosui, Setagaya-ku, Tokyo 156-8550, Japan
,
Haruki Mizoguchi 
a   Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan   Email: sakakura@okayama-u.ac.jp
,
Akira Sakakura  ∗
a   Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan   Email: sakakura@okayama-u.ac.jp
› Author AffiliationsThis work was supported in part by a Grant-in-Aid for Scientific Research (C) (No. 15K05123) from MEXT, the Naito Foundation, and the Okayama Foundation for Science and Technology.
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Abstract

C 1-Symmetric chiral ammonium salt catalysts induced a kinetic resolution of racemic α-nitrolactones through an asymmetric ester–amide exchange reaction. The corresponding amides were obtained with high enantioselectivities and high S (= k fast/k slow) values. This reaction system is a useful approach for obtaining carbocyclic quaternary α-nitroamides as chiral building blocks.

Key words

nitrolactones - kinetic resolution - hydrolysis - ester–amide exchange - quaternary amino acids - Brønsted acid catalysis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707303.
  • Supporting Information


Publication History

Received: 06 August 2020

Accepted after revision: 02 September 2020

Article published online:
08 October 2020

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  • References and Notes

  • 1 Fuji Y, Nakao R, Sugihara S, Fujita K, Araki Y, Kudoh T, Hayakawa I, Mizoguchi H, Sakakura A. Synlett DOI: in press; 10.1055/s-0040-1707302. 2020;
    Article in Thieme Connect
  • 2 For a review, see: Cativiela C, Ordóñez M. Tetrahedron: Asymmetry 2009; 20: 1
    CrossrefPubMed
    • 3a Okino T, Hoashi Y, Furukawa T, Xu X, Takemoto Y. J. Am. Chem. Soc. 2005; 127: 119
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    • 3b Okino T, Hoashi Y, Takemoto Y. J. Am. Chem. Soc. 2003; 125: 12672
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  • 4 See the Supporting Information for details.

      • For reviews, see:
    • 5a Kagan HB, Fiaud JC. Top. Stereochem. 1988; 18: 249
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    • 5b Keith JM, Larrow JF, Jacobsen EN. Adv. Synth. Catal. 2001; 343: 5
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    • 5c Robinson DE. J. E, Bull SD. Tetrahedron: Asymmetry 2003; 14: 1407
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    • 5d Vedejs E, Jure M. Angew. Chem. Int. Ed. 2005; 44: 3974
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  • 6 Because the absolute configuration of the recovered (+)-5a was 6aS, the absolute configuration of (–)-6a was assigned as 3R.
    CrossrefPubMed
  • 7 Because the reaction in Scheme 2 was conducted by using a mixture of 4b (25 mol%) and TFA (20 mol%), 5 mol% of 4b probably acted as a catalyst to promote the asymmetric hydrolysis of (±)-5a.
    CrossrefPubMed
  • 8 Qian Y, Ma G, Lv A, Zhu H.-L, Zhao J, Rawal VH. Chem. Commun. 2010; 46: 3004
    CrossrefPubMed
  • 9 Li W, Wu W, Yu F, Huang H, Liang X, Ye J. Org. Biomol. Chem. 2011; 9: 2505
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  • 10 Ogura Y, Akakura M, Sakakura A, Ishihara K. Angew. Chem. Int. Ed. 2013; 52: 8299
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  • 11 Ammonium salts of 4 were used as catalysts because the free amines 4 preferentially promoted the hydrolysis of 5a.
  • 12 Asymmetric Ester–Amide Exchange Reaction of (±)-5a (Table [2], Entry 12); Typical Procedure TfOH (0.5 μL, 5.6 μmol) and N 1-benzylglycinamide (7c; 7.7 mg, 0.051 mmol) were added to a solution of catalyst 4c (2.1 mg, 5.1 μmol) in toluene (1.2 mL) at rt, and the mixture was stirred for 5 min. The suspension was then cooled to –78 °C, (±)-5a (13.2 mg, 0.051 mmol) was added, and the resulting mixture was stirred at –78 °C for 24 h. The reaction was quenched by the addition of TFA (7.7 μL, 0.10 mmol), and the resulting mixture was purified by column chromatography [silica gel, hexane–acetone (3:1)] to give (–)-8ac (yield: 6.6 mg, 31%) and (+)-5a (yield: 8.5 mg, 64%). (1S,2R,3S,4R)-N-[2-(Benzylamino)-2-oxoethyl]-3-(2-hydroxyphenyl)-2-nitrobicyclo[2.2.1]hept-5-ene-2-carboxamide [(–)-8ac] White solid; mp 86.0–88.0 °C; [α]D 22 –142.1 (c 0.19, CHCl3) (95% ee). IR (film): 3324, 1655, 1539, 1456 cm–1. 1H NMR (600 MHz, CDCl3): δ = 7.50 (br s, 1 H), 7.4–7.2 (m, 3 H), 7.2–7.1 (m, 3 H), 7.1–7.0 (m, 2 H), 6.81 (t, J = 5.2 Hz, 1 H), 6.71 (dd, J = 0.8, 5.6 Hz, 1 H), 6.66 (dd, J = 2.0, 3.2 Hz, 1 H), 6.3–6.1 (m, 1 H), 6.08 (dd, J = 1.6, 3.6 Hz, 1 H), 4.31 (dd, J = 6.2, 15.0 Hz, 1 H), 4.2–4.1 (m, 2 H), 3.81 (br s, 1 H), 3.49 (dd, J = 5.1, 16.6 Hz, 1 H), 3.41 (dd, J = 5.2, 16.6 Hz, 1 H), 3.18 (br s, 1 H), 2.48 (d, J = 6.4 Hz, 1 H), 1.98 (d, J = 6.4 Hz, 1 H).13C NMR (100 MHz, CDCl3): δ = 168.2, 166.3, 154.7, 143.2, 137.2, 134.8, 128.7, 128.7, 127.6, 127.4, 127.4, 125.0, 121.0, 116.1, 104.5, 52.6, 49.0, 46.8, 46.2, 43.6, 43.6. HRMS (FAB): m/z [M + H]+ calcd for C23H24N3O5: 422.1710; found: 422.1698.
  • 13 The dimethylammonium group of the catalyst is more acidic than the thiourea group. In the Diels–Alder reaction,1 we proposed the formation of a hydrogen bond between the dimethylammonium group and the lactone group of 3-nitrocoumarin. In contrast, in the current reaction, the dimethylammonium group is proposed to interact preferentially with the amino group of 7c, because 7c is more basic than substrate 5.