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Synlett 2006(1): 0057-0060  
DOI: 10.1055/s-2005-922779
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Delphine Ménarda, Anne Vidala, Chantal Barthomeufb, Jacques Lebretonc, Pascal Gosselin*a
a Laboratoire de Synthèse Organique - UMR-CNRS 6011, Université du Maine, Avenue Olivier Messiaen, 72085 Le Mans Cedex 9, France
Fax: +33(2)43833902; e-Mail: pascal.gosselin@univ-lemans.fr;
b Laboratoire de Pharmacognosie et Biotechnologies, UMR-INSERM U-484, Faculté de Pharmacie, Université d’Auvergne, pl. H. Dunant, 63001 Clermont-Fd Cedex, France
c Laboratoire de Synthèse Organique - UMR-CNRS 6513, Département Chimie, Université de Nantes, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France
Further Information

Publication History

Received 5 October 2005
Publication Date:
16 December 2005 (online)

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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

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.