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.

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

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

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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.

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15

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

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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.

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