Helical Amide Derivatives: Synthesis by Insertion of Aliphatic ­Primary Amines into Benzo-Fused 2,2′-Diphenoquinones and Dia­stereomeric Resolution

Abstract

We have developed a method for synthesizing novel helical amide derivatives. Nucleophilic primary amines were inserted into benzo-fused 2,2′-biphenoquinones to form helical amides containing seven-membered rings. When optically pure primary amines were used in this reaction, a mixture of two amide diastereoisomers was obtained and separated into diastereomerically pure products by high-performance liquid chromatography. In contrast, the reaction of enantiomerically pure benzo-fused 2,2′-biphenoquinones with achiral aliphatic primary amines afforded enantiomerically pure helical amides with stereospecificity and retention of configuration.

Key words

helical amides - caprolactam - insertion reaction - seven-membered rings - diastereomeric resolution - asymmetric synthesis

Publication History

Received: 19 February 2022

Accepted after revision: 11 April 2022

Accepted Manuscript online:
11 April 2022

Article published online:
17 May 2022

• References and Notes

• 1a Amabilino DB. Chem. Soc. Rev. 2009; 38: 669
• 1b Chirality at the Nanoscale: Nanoparticles, Surfaces, Materials and More. Amabilino DB. Wiley-VCH; Weinheim: 2009
• 2a Grimme S, Harren J, Sobanski A, Vögtle F. Eur. J. Org. Chem. 1998; 1491
• 2b Urbano A. Angew. Chem. Int. Ed. 2003; 42: 3986
• 2c Collins SK, Vachon MP. Org. Biomol. Chem. 2006; 4: 2518
• 2d Rajca A, Miyasaki M. In Functional Organic Materials: Syntheses, Strategies and Applications . Müller T. J. J., Bunz U. H. F., Wiley-VCH; Weinheim: 2007: 547
• 2e Dumitrascu F, Dumitrescu DG, Aron I. ARKIVOC . 2010;
• 2f : 1
• 2g Shen Y, Chen C.-F. Chem. Rev. 2012; 112: 1463
• 2h Gingras M. Chem. Soc. Rev. 2013; 42: 968
• 2i Gingras M, Félix G, Peresutti R. Chem. Soc. Rev. 2013; 42: 1007
• 2j Gingras M. Chem. Soc. Rev. 2013; 42: 1051
• 3a Caronna T, Sinisi R, Catellani M, Malpezzi L, Meille SV, Mele A. Chem. Commun. 2000; 1139
• 3b Bunz UH. F. Angew. Chem. Int. Ed. 2010; 49: 5037
• 3c Tsuji H, Mitsui C, Ilies L, Sato Y, Nakamura E. J. Am. Chem. Soc. 2007; 129: 11902
• 3d Mitsui C, Soeda J, Miwa K, Tsuji H, Takeya J, Nakamura E. J. Am. Chem. Soc. 2012; 134: 5448
• 3e Nakano M, Niimi K, Miyazaki E, Osaka I, Takimiya K. J. Org. Chem. 2012; 77: 8099
• 4 Hossain MS, Akter M, Shahabuddin M, Salim MK.-i. Iimura, Karikomi M. Synlett 2022; 33: 277
• 5 Salim M, Akutsu A, Kimura T, Minabe M, Karikomi M. Tetrahedron Lett. 2011; 52: 4518
• 6 Salim M, Ubukata H, Kimura T, Karikomi M. Tetrahedron Lett. 2011; 52: 6591
• 7 Salim M, Kimura T, Karikomi M. Heterocycles 2013; 87: 547
• 8 Shahabuddin M, Salim M, Tomura M, Kimura T, Karikomi M. Tetrahedron Lett. 2016; 57: 5902
• 9 Shahabuddin M, Akutsu A, Kimura T, Karikomi M. Synthesis 2017; 49: 1547
• 10 Shahabuddin M, Ohgoshi K, Hossain MS, Kimura T, Karikomi M. Tetrahedron Lett. 2017; 58: 3704
• 11 Shahabuddin M, Hossain MS, Kimura T, Karikomi M. Tetrahedron Lett. 2017; 58: 4491
• 12 2a(a,d–f); General ProcedureA round-bottomed flask was charged with quinone 1a (48.7 mg, 0.10 mmol), anhyd CHCl₃ (1.5 mL), and the appropriate primary amine (3.2 equiv), and the mixture was stirred at rt. The color of the solution changed from red to brown, and the reaction was complete in 24 h. The mixture was concentrated and passed through a normal-phase column chromatography [silica gel, hexane–EtOAc (4:6)] to give the helical amide [2a(a,d–f)] as a brown solid major product (yield: 18–64%) and a white solid HEBPOL (3a–d) as a byproduct (yield: 6–81%).(P)-2a and (M)-2aBrown solid; yield: 64%; mp 245–250 °C. ¹H NMR (500 MHz, CDCl₃): δ = 0.75 (t, J = 7.5 Hz, 3 H), 1.22–1.39 (m, 1 H), 1.63–1.79 (m, 1 H), 3.20–3.32 (m, 1 H), 4.42–4.53 (m, 1 H), 6.48 (d, J = 9.5 Hz, 1 H), 6.58 (d, J = 8.5 Hz, 3 H), 6.72 (dd, J = 8.0 Hz, 2 H), 6.79 (d, J = 8.0 Hz, 1 H), 7.07–7.15 (m, 3 H), 7.31 (d, J = 9.5 Hz, 1 H), 7.33–7.37 (m, 2 H), 7.39–7.43 (m, 2 H), 7.45–7.50 (dd, J = 9.0 Hz, 2 H), 7.63 (d, J = 6.5 Hz, 1 H), 8.17 (d, J = 8.5 Hz, 1 H), 8.62 (d, J = 8.5 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 194.92, 166.09, 145.58, 143.17, 140.68, 139.97, 133.62, 132.82, 132.63, 132.39, 131.78, 131.47, 131.30, 130.84, 129.71, 129.31, 128.82, 128.15, 128.02, 127.99, 127.97, 127.83, 127.27, 127.19, 127.17, 126.89, 126.69, 126.57, 126.47, 126.35, 125.55, 125.46, 125.28, 125.25, 124.73, 124.32, 55.33, 33.47, 11.14. HRMS (EI): m/z [M]⁺ calcd for C₃₉H₂₇NO₂: 541.2042; found: 541.2093. Chiral HPLC {Chiral PAK IG [CHCl₃–hexane (2:3), 5 μL, 0.8 mL/min; λ = 310 nm]}: t _R = 12.32 min [(P)-2aa], 8.16 min [(M)-2aa].