Application of One-Pot Three-Component Condensation Reaction for the Synthesis of New Organophosphorus–Sulfur Macrocycles

Abstract

An efficient approach has been developed for the synthesis of new phosphorus–sulfur heterocycles by a one-pot three-component condensation reaction of a four-membered-ring thionation reagent [Lawesson’s reagent or its ferrocene analogue (2,4-diferrocenyl-1,3,2,4-diathiadiphosphetane 2,4-disulfide)], an alkane- or arenedithiol, and a dihaloalkane at room temperature in the presence of triethylamine. The simple synthesis method with mild conditions (room temperature and normal reactant concentrations) enhances further the application of the multicomponent reaction in the preparation of novel phosphorus–sulfur heterocycles. Six representative X-ray structures confirmed the formation of these macrocycles.

Key words

multicomponent reactions - macrocycles - phosphorus–sulfur heterocycles - Lawesson’s reagent - dithiols - dihaloalkanes

• References and Notes

• 1a Raymo FM. Stoddart JF. Chem. Rev. 1999; 99: 1643
• 1b Shu Y.-Z. J. Nat. Prod. 1998; 61: 1053
• 2a Driggers EM. Hale SP. Lee J. Terrett NK. Nat. Rev. Drug Discov. 2008; 7: 608
• 2b Marsault E. Peterson ML. J. Med. Chem. 2011; 54: 1961
• 2c Giordanetto F. Kihlberg J. J. Med. Chem. 2014; 57: 278
• 2d Yudin AK. Chem. Sci. 2015; 6: 30
• 2e Down S. Dewal MB. Sobransingh D. Paderes M. Wibowo AC. Smaith MD. Krause JA. Pellechia PJ. Shimizu LS. J. Am. Chem. Soc. 2011; 133: 7025
• 2f Montenegro J. Ghadiri MR. Granja JR. Acc. Chem. Res. 2013; 46: 2955
• 2g Griffiths KE. Stoddart JF. Pure Appl. Chem. 2008; 80: 485
• 2h Evans NH. Beer PD. Chem. Soc. Rev. 2014; 43: 4658
• 2i Xue M. Yang Y. Chi X. Yan X. Huang F. Chem. Rev. 2015; 115: 7398
• 3 Comprehensive Supramolecular Chemistry . Lehn JM. Atwood JL. Davies JE. D. MacNicol DD. Vogtle F. Pergamon; Oxford: 1996
• 4 Cetinkaya B. Hitchcock PB. Lappert MF. Torne AJ. Goldwhite H. J. Chem. Soc., Chem. Commun. 1982; 691
• 5 Yoshifuji M. Higeta N. An D.-L. Toyota K. Chem. Lett. 1998; 27: 17
• 6 Hanessian S. Maianti JP. Chem. Commun. 2010; 46: 2013
• 7 Collins JC. Farley KA. Limberakis C. Liras S. Price D. James K. J. Org. Chem. 2012; 77: 11079
• 8 Pedersen DS. Abell A. Eur. J. Org. Chem. 2011; 2399
• 9 Bogdan AR. Jerome SV. Houk KN. James K. J. Am. Chem. Soc. 2012; 134: 2127
• 10 Pascu M. Ruggi A. Scopelliti R. Severin K. Chem. Commun. 2013; 49: 45
• 11a Sommen GL. In Comprehensive Heterocyclic Chemistry III . Vol. 14, Chap. 16. Katritzky AR. Ramsden C. Scriven EF. V. Taylor R. Elsevier; Oxford: 2008: 863
• 11b Shestopalov AM. Shestopalov AA. In Comprehensive Heterocyclic Chemistry III . Vol 14, Chap. 17. Katritzky AR. Ramsden C. Scriven EF. V. Taylor R. Elsevier; Oxford: 2008: 900
• 12 Tomoda S. Iwaoka M. J. Chem. Soc., Chem. Commun. 1990; 231
• 13 Li JL. Meng JB. Wang YM. Wang JT. Matsuura T. J. Chem. Soc., Perkin Trans.1 2001; 1140
• 14 Ishii A. Furusawa K. Omata T. Nakyama J. Heteroat. Chem. 2002; 13: 351
• 15 Sankar AU. R. Reddy SS. Reddy GC. S. Reddy MV. N. Raju CN. Med. Chem. Res. 2011; 20: 962
• 16 Cordova-Reyes I. VandenHoven E. Mohammed A. Pinto BM. Can. J. Chem. 1995; 73: 113
• 17 Zeng X. Han X. Chen L. Li Q. Xu F. He X. Zhang Z.-Z. ­Tetrahedron Lett. 2002; 43: 131
• 18 Hua G. Du J. Slawin AM. Z. Woollins JD. Chem. Eur. J. 2016; 22: 7782
• 19 Hua G. Du J. Cordes DB. Slawin AM. Z. Woollins JD. J. Org. Chem. 2016; 81: 4210
• 20 Hua G. Slawin AM. Z. Randall RA. M. Corde DB. Crawford L. Bühl M. Woollins JD. Chem. Commun. 2013; 49: 2619
• 21 Macrocycles 1–12 and 14; General Procedure A suspension of the appropriate dithiol (1.0 mmol), dihaloalkane (1.0 mmol), Et₃N (2.0 mmol), and LR (0.44 g, 1.0 mmol) or FcLR (0.56 g, 1.0 mmol) in anhyd THF (60 mL) was stirred under N₂ at r.t. for 24 h to give a reddish yellow or pale-yellow suspension. Insoluble solids were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was dissolved in CH₂Cl₂ (~2 mL) and purified by column chromatography (silica gel, CH₂Cl₂). The unexpected nine-membered-ring product 4 was obtained as a byproduct in 25% and 30% yield in the syntheses of 5 and 9, respectively. Two diastereomers were separated completely in the cases of 10 and 12. Compound 1 (Table [1]) White foam; yield: 525 mg (80%; two diastereoisomers were found in ~1:1 intensity ratio). ¹H NMR (400.1 MHz, CD₂Cl₂): δ = 8.03–7.71 (m, 8 H), 8.03–7.71 (m, 8 H), 7.29–6.88 (m, 8 H), 4.09–3.96 (m, 8 H), 3.78 (s, 6 H), 3.76 (s, 6 H). ¹³C NMR (100.6 MHz, CD₂Cl₂): δ = 165.4, 164.2, 134.9, 133.7, 133.6, 133.4, 131.8, 131.7, 129.1, 128.8, 115.0, 114.9, 114.8, 114.7, 56.1, 56.0, 35.9, 35.7. ³¹P NMR (162.0 MHz, CD₂Cl₂): δ = 95.1 and 95.0. MS (EI⁺): m/z = 656 [M]⁺. HRMS (EI⁺): m/z [M]⁺ calcd for C₂₄H₂₂N₂O₂P₂S₇: 655.9201; found: 655.9196. Compound 8 Dark-yellow solid; yield: 332 mg (40%); (two diastereomers were found in ~1:1 intensity ratio). ¹H NMR (400.1 MHz, ­CD₂Cl₂): δ = 7.34–7.10 (m, 16 H), 4.62–4.60 (m, 16 H), 4.32 (s, 10 H), 4.31 (s, 10 H), 4.11–3.89 (m, 8 H), 3.66–3.55 (m, 8 H). ¹³C NMR (100.6 MHz, CD₂Cl₂): δ = 137.8, 137.7, 130.8, 130.2, 129.4, 128.9, 128.6, 128.3, 78.4 [d, J(P,C) = 101 Hz], 78.2 [d, J(P,C) = 102 Hz], 72.4, 72.3, 71.9, 71.7, 71.2, 70.9, 38.0, 35.6. ³¹P NMR (162.0 MHz, CD₂Cl₂): δ = 82.0 and 81.4. MS (EI⁺): m/z = 833 [M + H]⁺. HRMS (CI⁺): m/z [M + H]⁺ calcd for C₃₆H₃₅Fe₂P₂S₆: 832.9237; found: 832.9233.
• 22 Cava MP. Levinson MI. Tetrahedron 1985; 41: 5061
• 23 Lecher HZ. Greenwood RA. Whitehouse KC. Chao T. H. J. Am. Chem. Soc. 1956; 78: 5018
• 24 Chavdarian CG. Phosphorus, Sulfur Silicon Relat. Elem. 1987; 31: 77
• 25 Shabana R. Phosphorus, Sulfur Silicon Relat. Elem. 1987; 29: 293
• 26 CCDC 1815050–1815055 contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
• 27 Hua G. Randall RA. M. Slawin AM. Z. Woollins JD. Tetrahedron 2013; 69: 5299