Sharpless Asymmetric Dihydroxylation on α,β-Unsaturated Diazoketones: A New Entry for the Synthesis of Disubstituted Furanones

Published as part of the ISHC Conference Special Section

Abstract

The synthesis of enantiomerically pure 4,5-disubstituted 2-furanones is accomplished in three steps from aldehydes. The steps involve a highly enantioselective Sharpless asymmetric dihydroxylation of α,β-unsaturated diazoketones, followed by a photochemical Wolff rearrangement.

Key words

unsaturated diazoketones - Sharpless dihydroxylation - furanones - Wolff rearrangement - photochemistry - asymmetric synthesis

• References and Notes

• 1 Burtoloso AC. B. Dias RM. P. Bernardim B. Acc. Chem. Res. 2015; 48: 921
• 2 Pinho VD. Burtoloso AC. B. J. Org. Chem. 2011; 76: 289
• 3 Rosset IG. Burtoloso AC. B. J. Org. Chem. 2013; 78: 9464
• 4 Rulev AY. Russ. Chem. Rev. 2011; 80: 197
• 5a Wolff L. Justus Liebigs Ann. Chem. 1902; 325: 129
• 5b Kirmse W. Eur. J. Org. Chem. 2002; 2193
• 5c Gill GB. In Comprehensive Organic Synthesis . Fleming BM. T. Pergamon; Oxford: 1991: 887
• 6a Gillingham D. Fei N. Chem. Soc. Rev. 2013; 42: 4918
• 6b Ford A. Miel H. Ring A. Slattery CN. Maguire AR. Mckervey MA. Chem. Rev. 2015; 115: 9981
• 6c Ye T. Mckervey MA. Chem. Rev. 1994; 94: 1091
• 6d Doyle MP. Mackervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: from Cyclopropanes to Ylides. Wiley; New York: 1998
• 7 Vanrheenen V. Kelly RC. Cha DY. Tetrahedron Lett. 1976; 23: 1973
• 8a Smith DA. Reynolds DN. Woo LK. J. Am. Chem. Soc. 1993; 115: 2511
• 8b Demonceau A. Lemoine CA. Noels AF. Tetrahedron Lett. 1996; 37: 1025
• 9a Sharpless KB. Amberg W. Benani YL. Crispino GA. Hartung J. Jeong K-S. Kwong H.-L. Morikawa K. Wang Z.-M. Xu D. Zhang X.-L. J. Org. Chem. 1992; 57: 2768
• 9b Kolb H. VanNieuwenhze MS. Sharpless KB. Chem. Rev. 1994; 94: 2483
• 10 Minato M. Yamamoto K. Tsuji J. J. Org. Chem. 1990; 55: 766
• 11 Eames J. Mitchell HJ. Nelson A. O’brien P. Warren S. Wyatt P. J. Chem. Soc., Perkin Trans. 1 1999; 1095
• 12 Junttila MH. Hormi OO. E. J. Org. Chem. 2009; 74: 3038
• 13 Jacobsen EN. Markó I. Mungall WS. Schröder G. Sharpless KB. J. Am. Chem. Soc. 1988; 110: 1968
• 14 General Procedure for Asymmetric Dihydroxylation of α,β-Unsaturated Diazoketones: To a 3 mL glass vial containing a magnetic stirrer and fitted with a cap, was added 418 mg of an oxidizing mixture containing K₃Fe(CN)₆ (6 equiv, 286.8 mg, 0.87 mmol), K₂CO₃ (6 equiv, 120.4 mg, 0.87 mmol), (DHQ)₂PHAL (11.3 mg, 0.0145 mmol), and K₂OsO₂(OH)₄ (0.214 mg, 0.0581 mmol). Then, a t-BuOH/H₂O mixture (1:2, 1.5 mL) was added and the mixture was vigorously stirred. CH₃SO₂NH₂ (3 equiv, 41.4 mg, 0.435 mmol) and α,β-unsaturated diazoketone (1 equiv, 0.145 mmol) were added and the mixture was allowed to react for 10 hours. After this time, another portion of the oxidizing mixture (418 mg) and CH₃SO₂NH₂ (41.4 mg) were added and the mixture was stirred for an additional 10 h (progress of the reaction monitored by TLC). After this time, H₂O (30 mL) was added to the reaction mixture and the aqueous phase was extracted with a mixture of CH₂Cl₂ and 2-propanol (3:1, 2 × 10 mL), followed by another extraction with pure CH₂Cl₂ (3 × 10 mL) (conventional work-up with Na₂SO₃ and base led to degradation of the products). The organic phase was dried over Na₂SO₄, filtered and concentrated. The products were purified by flash chromatography (silica gel, 1:1 hexane/EtOAc) to afford the pure solid diols (Note: all racemic diols were synthesized by using DABCO as the ligand in similar yields; For larger scales, the conditions described in Table 1, entry 14, was preferred). (3R,4S)-1-Diazo-3,4-dihydroxy-4-phenylbutan-2-one [(+)-2]: Yield: 16 mg (53% yield; 57% based on recovery of starting material; diazoketone recovered: 1.5 mg); crystalline yellow solid; mp 97–99 °C; R_f = 0.15 (silica gel, 1:1 EtOAc/hexane); IR: 3332, 3268, 3118, 2918, 2115, 1599, 1363, 1300, 1140, 1047, 708 cm^–1; ¹H NMR (500 MHz, CD₃CN): δ = 7.40–7.32 (m, 4 H), 7.27 (tt, J = 7.2, 1.3, 1.3 Hz, 1 H), 5.88 (s, 1 H), 4.95 (dd, J = 5.5, 2.9 Hz, 1 H), 4.16 (d, J = 3.3 Hz, 1 H), 3.74 (d, J = 6.8 Hz, 1 H), 3.64 (d, J = 5.9 Hz, 1 H); ¹³C NMR (126 MHz, CD₃CN): δ = 196.6, 142.4, 128.9, 128.3, 127.4, 80.2, 74.8, 54.5; [α] _d ²⁵ +141.6 (c = 0.5, MeOH); HRMS (ESI-TOF): m/z [M⁺+Na] calcd for C₁₀H₁₀N₂NaO₃: 229.05836; found: 229.05801; HPLC conditions: Chiralpak AD-H, 1:1 (n-hexane/IPA); flow rate: 1.0 mL/min; λ = 254 nm; t _R = 4.60 (minor), 8.74 (major) min; e.r. = 99:1.
• 15 Carter NB. Nadany AE. Sweeney JB. J. Chem. Soc., Perkin Trans. 1 2002; 2324
• 16a Shah NC. Pringle SD. Donan PT. Struthers AD. J. Hypertens. 2007; 25: 2345
• 16b Raju R. Gromyko O. Fedorenko V. Herrmann J. Luzhetskyy A. Müller R. Tetrahedron Lett. 2013; 54: 900
• 16c Yabu Y. Yoshida A. Suzuki T. Nihei C. Kawai K. Minagawa N. Hosokawa T. Nagai K. Ohta N. Parasitol. Int. 2003; 52: 155
• 17 Ledroit V. Debitus C. Lavaud C. Massiot G. Tetrahedron Lett. 2003; 44: 225
• 18a Kuroda I. Musman M. Ohtani II. Ichiba T. Tanaka J. Gravalos DC. Higa T. J. Nat. Prod. 2002; 65: 1505
• 18b Martinková M. Gonda J. Carbohydr. Res. 2016; 423: 1
• 19 General Procedure for the Synthesis of 4,5-Disubstituted 2-Furanones: In a quartz cell of 1 cm light path, containing a magnetic stirrer and fitted with a rubber septum, was added the diol (0.1 mmol) and anhydrous acetonitrile (2.5 mL, 0.04 M) under argon atmosphere. The reaction mixture was irradiated with an Osram 150 xenon arc lamp for 10 h under magnetic stirring at room temperature. The solvent was then removed under reduced pressure in a rotatory evaporator and the crude product was purified by flash chromatography with a short pad of silica (CHCl₃ as the eluent). Lactones were obtained as solids. (4S,5S)-4-Hydroxy-5-phenyldihydrofuran-2(3H)-one [(+)-10]: Yield: 16 mg (90% yield); pale-yellow solid; mp 78–80 °C; R_f = 0.2 (silica gel, CHCl₃, twice eluted); IR: 3432, 2929, 1773, 1454, 1310, 1154, 1075, 1020, 742, 699 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ = 7.47–7.43 (m, 2 H), 7.42–7.37 (m, 3 H), 5.52 (d, J = 3.5 Hz, 1 H), 4.63 (m, 1 H), 2.90 (dd, J = 17.5, 5.1 Hz, 1 H), 2.74 (d, J = 17.5 Hz, 1 H), 1.48 (s, 1 H); ¹³C NMR (101 MHz, CDCl₃): δ = 175.3, 132.3, 129.1, 129.0, 126.3, 85.0, 70.2, 38.5; [α] _d ²⁵ +34.4 (c = 0.98, MeOH); HPLC conditions: Lux^® amilose-2 8:2 (n-hexane/IPA); flow rate: 1.1 mL/min; λ = 206 nm; t _R = 18.58 (major), 22.06 (minor) min; e.r. = 98:02.
• 20a Wang Z.-M. Zhang X.-L. Sharpless KB. Sinha SC. Sinha-Bagchi A. Keinan E. Tetrahedron Lett. 1992; 33: 6407
• 20b Reddy GV. Sreevani V. Iyengar DS. Tetrahedron Lett. 2001; 42: 531
• 20c Eissler S. Nahrwold M. Neumann B. Stammler H.-G. Sewald N. Org. Lett. 2007; 9: 817