Mercuric Triflate·(TMU)₂ Catalyzed Cyclization of a Propargylic Ketone into a Monosubstituted Furan

Abstract

Formation of a furan derivative was observed in the course of a synthetic approach towards a new carotenoid metabolite, starting from a propargylic ketone, in the presence of mercuric triflate-tetramethylurea complex.

Key words

alkynes - ketones - furans - catalysis - addition reactions

References and Notes

• 1 Roussakis C, Bergé JP, Baud JP, Chevolot L, and Durand P. inventors; WO 0044718 A1,  20000803.  ; Chem. Abstr. 2000, 133, 134246
• 2 Bergé JP. Bourgougnon N. Carbonnelle D. Le Bert V. Tomasoni C. Durand P. Roussakis C. Anticancer Res.  1997,  17:  2115 
• 4a Nagpal A. Unny R. Joshi YC. Heterocycl. Commun.  2001,  32:  589 
• 4b Simoni D. Invidiata FP. Rondanin R. Grimaudo S. Cannizzo G. Barbusca E. Porretto F. D’Alessandro N. Tolomeo M. J. Med. Chem.  1999,  42:  4961 
• 4c Alekseev VV. Zelinin KN. Yakimovich SI. Russ. J. Org. Chem.  1995,  31:  705 
• 4d Ellis GP. The Chemistry of Heterocyclic Compounds, In Chromanones and Chromones   Vol. 33:  Ellis GP. J. Wiley and Sons; USA: 1977.  p.495 
• 4e Raston CL. Salem G. J. Chem. Soc., Chem. Commun.  1984,  1702 
• 4f Buchanan JG. Sable HZ. In Selective Organic Transformations   Vol. 2:  Thyagarajan BS. Wiley-Interscience; New York: 1972.  p.1 
• 5 Garnovskii AD. Kharixov BI. Blanco LM. Garnovskii DA. Burlov AS. Vasilchenko IS. Bondarenko GI. J. Coord. Chem.  1999,  46:  365 
• 6a Beck AK. Hoekstra MS. Seebach D. Tetrahedron Lett.  1977,  18:  1187 
• 6b Tang Q. Sen SE. Tetrahedron Lett.  1998,  39:  2249 
• 6c Katritzky AR. Pastor A. J. Org. Chem.  2000,  65:  3679 
• 6d Le Roux C. Mandrou S. Dubac J. J. Org. Chem.  1996,  61:  3885 ; and references cited therein
• For recent references, see:
• 6e Wiles C. Watts P. Haswell SJ. Pombo-Villar E. Tetrahedron Lett.  2002,  43:  2945 
• 6f Kel’in AV. Curr. Org. Chem.  2003,  7:  1 
• 7 Ballini R. Bartoli G. Synthesis  1993,  965 
• 8 Fargeas V. Baalouch M. Metay E. Baffreau J. Ménard D. Gosselin P. Bergé J.-P. Barthomeuf C. Lebreton J. Tetrahedron  2004,  60:  10359 
• 9 Sondheimer F. Amiel Y. Gaoni Y. J. Am. Chem. Soc.  1961,  84:  270 
• 10 Stacy GW. Mikulec RA. Org. Synth., Coll. Vol. IV  1963,  13 
• 11 Nishizawa M. Skwarczynski M. Imagawa H. Sugihara T. Chem. Lett.  2002,  12 
• 14 Larock RC. Harrison LW. J. Am. Chem. Soc.  1984,  106:  4218 
• 16 Sniady A. Wheeler KA. Dembinski R. Org. Lett.  2005,  7:  1769 
• 17 Hashmi ASK. Bats JW. Choi J.-H. Schwarz L. Tetrahedron Lett.  1998,  39:  7491 
• 20 Zeni G. Larock RC. Chem. Rev.  2004,  104:  2285 ; and references therein
• 21a Marshall JA. Bartley GS. J. Org. Chem.  1994,  59:  7169 
• 21b Aucagne V. Amblard F. Agrofoglio LA. Synlett  2004,  2406 
• 22a Hashmi ASK. Schwarz L. Choi J.-H. Frost TM. Angew. Chem. Int. Ed.  2000,  39:  2285 
• 22b Yao T. Zhang X. Larock RC. J. Am. Chem. Soc.  2004,  126:  11164 
• 23 Kel’in AV. Gevorgyan V. J. Org. Chem.  2002,  67:  95 
• 24 Barluenga J. Vazquez-Villa H. Ballesteros A. Gonzalez JM. J. Am. Chem. Soc.  2003,  125:  9028 
• 25a Brown CD. Chong JM. Shen L. Tetrahedron  1999,  55:  14233 
• 25b Obrecht D. Helv. Chim. Acta  1989,  72:  447 
• 26a Arcadi A. Marinelli F. Pini E. Rossi E. Tetrahedron Lett.  1996,  37:  3387 
• 26b Vieser R. Eberbach W. Tetrahedron Lett.  1995,  36:  4405 
• 27 Imagawa H. Kurisaki T. Nishizawa M. Org. Lett.  2004,  6:  3679 
• 28a Hashmi ASK. Schwarz L. Bats JW. J. Prakt. Chem.  2000,  342:  40 
• 28b Hashmi ASK. Schwarz L. Bolte M. Tetrahedron Lett.  1998,  39:  8969 

3

The preparation of aldehyde 2 from cyclohexane-1,4-diol will be reported in a forthcoming full paper.

12

The red form of mercuric oxide was used although Nishizawa et al. (see ref. 11) described the reaction with the yellow form.

13

Typical Experimental Procedure for the Synthesis of Aldehydes 4 and 5 and Furan 11.
Tf₂O (8 µL, 0.046 mmol, 0.11 equiv) and TMU (11 µL, 0.092 mmol, 0.22 equiv) were added in succession at r.t. to a stirred suspension of mercuric oxide (red, 10 mg, 0.046 mmol, 0.11 equiv) in dry MeCN (1 mL). After 10 min, a solution of homopropargylic alcohol 3 (132 mg, 0.41 mmol, 1 equiv) in dry CH₂Cl₂ (0.5 mL) was added, immediately followed by H₂O (22 µL, 1.22 mmol, 3 equiv) and the mixture was stirred 24 h at r.t. After addition of a 1:1 mixture of sat. aq NaHCO₃ and brine (2 mL), the mixture was extracted with EtOAc (4 × 10 mL). The combined organic phases were washed with a 10% HCl solution (10 mL), dried over anhyd Na₂SO₄ and the solvent was evaporated. Purification by flash chromatography (elution with cyclohexane-EtOAc, 9:1 to 6:4) afforded OTBS-protected aldehydes (13 mg, 10%, partly separated) and unprotected aldehydes 4 and 5 (28 mg, 33%, partly separated), as colorless oils.
Analytical data for aldehyde 4 (ca. 1:2 Z:E mixture): R _f = 0.40 (eluent: cyclohexane-EtOAc, 6:4). IR (film): 3407, 2953, 2922, 2858, 1667,1458, 1364, 1190, 1117, 1048, 909, 877, 834 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.00 and 1.03 [2 s, 6 H, (Me)₂-C, 1:3], 1.02 and 1.05 [2 s, 6 H, (Me)₂-C, 2:3], 1.26 (br s, 1 H, OH), 1.35 (m, 1 H), 1.78 (m, 2 H), 1.91 (br s, 3 H, Me-C=, 1:3), 2.11 (br s, 3 H, Me-C=, 2:3), 2.19 (m, 1 H), 2.82 (br s, 2 H, CH ₂ CH=, 2:3), 3.21 (br s, 2 H, CH ₂ CH=, 1:3), 3.98 (m, 1 H, CHOH), 5.26 (br s, 1 H, CH₂CH=), 5.88 (d, J = 8.1 Hz, 1 H, CH-CHO, 2:3), 5.99 (d, J = 8.1 Hz, 1 H, CHCHO, 1:3), 9.95 (d, J = 8.1 Hz, 1 H, CHO, 1:3), 9.99 (d, J = 8.1 Hz, 1 H, CHO, 2:3). ¹³C NMR (100 MHz, CDCl₃): δ = 17.2 (q), 24.8 (q), 29.5 (q), 29.6 (q), 29.8 (q), 31.27 (q), 31.31 (q), 34.4 (s), 34.5 (s), 37.7 (t), 37.9 (t), 40.2 (t), 46.0 (t), 48.6 (t), 65.99 (d), 66.03 (d), 128.2 (s), 128.6 (d), 128.7 (s), 129.8 (d), 135.2 (d), 136.1 (d), 161.5, 161.8 (s), 190.9 (d), 191.4 (d). GCMS (EI, 70 eV, minor diastereomer): m/z (%) = 208 (5), 190 (38), 175 (79), 157 (64), 137 (84), 119 (56), 105 (80), 91 (85), 77 (55), 43 (50), 41 (90), 39 (100). GCMS (EI, 70 eV, major diastereomer): m/z (%) = 208 (2), 175 (36), 157 (37), 147 (69), 119 (45), 107(100), 105(68), 91 (46), 79 (33), 55 (49), 41 (64), 39 (68). GCMS (CI+, i-C₄H₁₀, both diastereomers): m/z = 209 [MH⁺], 191, 173, 163, 147, 109, 95, 69. HRMS (EI): m/z calcd for C₁₃H₂₀O₂: 208.1463; found: 208.1454. Analytical data for OTBS-protected aldehyde 5: R _f = 0.52 (eluent: PE-Et₂O, 9:1). IR (film): 2955, 2928, 2857, 1727, 1643, 1471, 1381, 1360, 1256, 1080, 836, 775, 666 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.06 [s, 6 H (Me)₂-Si], 0.88 (s, 9 H, t-Bu-Si), 0.97 and 0.99 [2 s, 2 × 3H, (Me)₂-C], 1.34 and 1.62 [2 m, 2 H, CH ₂ -C(Me)₂], 1.79 and 2.04 (2 m, 2 H, CH ₂ C=CH₂), 2.68 (br s, 2 H, CH ₂ CH=C), 3.01 (br s, 2 H, CH ₂ CH=O), 3.90 (dddd, J = 11.3, 9.1, 5.5, 3.6 Hz, 1 H, CHOSi), 4.95 (br s, 1 H, CH ₂=C), 5.06 (br s, 1 H, =CHCH₂), 5.15 (br s, 1 H, CH ₂=C), 9.59 (t, J = 2.5 Hz, 1 H, CHO). ¹³C NMR (100 MHz, CDCl₃): δ = -4.6 (q), 18.2 (s), 26.0 (q), 29.5 (q), 31.2 (q), 34.2 (s), 38.0 (t), 45.5 (t), 46.4 (t), 49.9 (t), 66.8 (d), 116.6 (t), 129.4 (s), 134.9 (d), 138.7 (s), 199.9 (d). HRMS (ESI): m/z calcd for C₁₉H₃₄O₂NaSi: 345.2226. Found: 345.2221.

15

Depending on reaction time, small amounts of TBS-protected alcohols 4 and 5 were also isolated.

18

The result is the same when the crude propargylic ketone 9 or the purified allene 10 is used for the hydration reaction.

19

Analytical data for 11 (ca. 3:2 mixture of cis:trans diastereoisomers): R _f = 0.34 (eluent: PE-Et₂O, 6:4). IR (film): 3352, 2954, 2926, 2866, 1715, 1647, 1588, 1501, 1461, 1364, 1258, 1149, 1044, 1015, 899, 799, 730, 597 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.80, 0.86, 0.98, 0.99 (4 × s, 3 H, Me), 1.42 [br t, J = 12.5 Hz, 1 H, CH ₂C(Me)₂, 2:5], 1.61 [ddt, J = 12.7, 4.7, 1.3 Hz, 1 H, CH ₂C(Me)₂, 3:5], 1.75 (br s, 1 H, OH), 1.80 [br t, J = 12.7 Hz, 1 H, CH ₂C(Me)₂, 3:5], 1.87 [ddd, J = 12.5, 4.4, 2.1 Hz, 1 H, CH ₂C(Me)₂, 2:5], 2.07 (br t, J = 12.0 Hz, 1 H, CH ₂C=CH₂, 2:5), 2.46 (br t, J = 12.7 Hz, 1 H, CH ₂C=CH₂, 3:5), 2.57 (dd, J = 12.7, 4.5 Hz, 1 H, CH ₂C=CH₂, 3:5), 2.75 (ddd, J = 12.0, 4.9, 2.2 Hz, 1 H, CH ₂C=CH₂, 2:5), 3.14 [s, 1 H, CHC(Me₂), 3:5], 3.23 [s, 1 H, CHC(Me₂), 2:5], 3.91 (m, 1 H, CHOH), 4.58 and 4.90 (2 × br s, 2 H, CH ₂ =C, 2:5), 4.83 and 4.86 (2 × br s, 2 H, CH ₂ =C, 3:5), 6.06 (d, J = 3.1 Hz, 1 H, CH=CO, 3:5), 6.08 (d, J = 3.1 Hz, 1 H, CH=CO, 2:5), 6.26 (dd, J = 3.1, 1.8 Hz, 1 H, CH=CHO, 3:5), 6.32 (dd, J = 3.1, 1.8 Hz, 1 H, CH=CHO, 2:5), 7.29 (d, J = 1.8 Hz, 1 H, =CHO, 3:5), 7.34 (d, J = 1.8 Hz, 1 H, =CHO, 2:5). ¹³C NMR (100 MHz, CDCl₃): δ = 22.5, 28.1, 28.7, 30.3 (4 q, Me), 35.5 [s, C(Me)₂, major], 36.1 [s, C(Me)₂, minor], 41.8 (t, CH₂C=, major), 44.4 [t, CH₂C(Me)₂, major], 45.5 (t, CH₂C=, minor), 50.7 [t, CH₂C(Me)₂, minor], 53.6 [2 d, CHC(Me)₂], 67.6 (d, CHO, minor), 67.9 (d, CHO, major), 106.4 (d, CH=CO, major), 108.2 (d, CH=CO, minor), 109.9 (2 d, CH=CHO), 111.9 (t, CH₂=C, minor), 113.0 (t, CH₂=C, major), 140.7 (d, =CHO, major), 140.9 (d, =CHO, minor), 144.4 and 145.0 (2 s, C=CH₂), 154.0 (s, =CO, minor), 156.3 (s, =CO, major). GCMS (EI, 70 eV, cis-diastereomer, major): m/z (%) = 206 (18), 188 (66), 173 (36), 145 (26), 122 (35), 121 (100), 107 (22), 93 (34), 91 (34), 77 (28), 41 (36), 39 (39). GCMS (EI, 70 eV, trans-diastereomer, minor): m/z (%) = 206 (57), 188 (38), 173 (67), 145 (33), 122 (33), 121 (100), 107 (23), 93 (37), 91 (39), 77 (33), 41 (42), 39 (47). GCMS (CI+, MeCN): m/z = 207 [MH⁺], 189, 161, 139, 121, 95, 65. HRMS (EI): m/z calcd for C₁₃H₁₈O₂: 206.1307. Found: 206.1313.