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Synlett 2003(14): 2123-2128  
DOI: 10.1055/s-2003-42108
LETTER
© Georg Thieme Verlag Stuttgart · New York

Diastereoselective Ruthenium-Catalyzed [2+2] Cycloadditions between Bicyclic Alkenes and a Chiral Propargylic Alcohol and its Derivatives

Karine Villeneuve, Robert W. Jordan, William Tam*
Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Department of Chemistry and Biochemistry, University of Guelph, Guelph, Ontario, N1G 2W1, Canada
Fax: +1(519)7661499; e-Mail: wtam@uoguelph.ca;
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Publication History

Received 25 September 2003
Publication Date:
29 October 2003 (online)

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Abstract

Diastereoselective ruthenium-catalyzed [2+2] cyclo­additions of symmetrical bicyclic alkenes and a chiral propargylic alcohol or its derivatives were investigated. The cycloadditions were found to be highly chemo- and stereoselective giving anti-exo-cycloadducts in moderate to good yields. Diastereoselectivities of 58:42 to 84:16 were observed with chiral propargylic alcohol 2f and its derivatives 2a-g.

Key words

ruthenium - [2+2] cycloaddition - diastereoselectivity - alkene - alkyne

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Representative Experimental: (i) Ru-catalyzed [2+2] cycloadditions between 5 and 2f (Table [2] , entry 10): A mixture of norbornadiene 5 (164 µL, 1.52 mmol), alkyne 2f (71.8 mg, 0.51 mmol), and THF (0.3 mL) in an oven-dried vial was added via a cannula to an oven-dried screw-cap vial containing Cp*RuCl(COD) (weighed out from a dry box, 11.6 mg, 0.0305 mmol) under nitrogen. The oven-dried vial was rinsed with THF (0.3 mL). The reaction mixture was stirred in the dark at 25 ºC for 72 h. The crude product was purified by column chromato-graphy (EtOAc:hexanes = 1:9) to give an inseparable mixture of diastereoisomers 6f and 7f (107.5 mg, 0.459 mmol, 90%, 6f:7f (dr) = 82:18 measured by 1H NMR and GC) as a colorless oil. Rf = 0.42 (EtOAc:hexanes = 1:4); GC (HP-1 column): retention time for major isomer = 17.23 min, retention time for minor isomer = 17.35 min. IR (CH2Cl2): 3428 (br s), 3067 (w), 2983 (m), 1722 (s), 1675 (m), 1370 (m), 267 (s) cm-1. 1H NMR (400 MHz, CDCl3):
δ = 6.17 (dd, 1 H, J = 5.1, 3.0 Hz), 6.11 (dd, 1 H, J = 5.5, 2.9 Hz), 5.16 (br s, 0.18 H), 5.09 (br s, 0.82 H), 4.58 (q, 1 H, J = 6.8 Hz), 4.22 (q, 2 H, J = 7.1 Hz), 2.63 (br s, 1 H), 2.59 (br s, 0.18 H), 2.51 (br s, 0.82 H), 2.44 (m, 1 H), 2.33 (m, 1 H), 1.29-1.40 (m, 8 H). 13C NMR (100 MHz, APT, CDCl3): major diastereomer δ = 170.2, 164.2, 136.3, 135.3, 131.4, 65.7, 60.8, 43.8, 42.3, 39.7, 38.6, 37.9, 21.3, 14.2; minor diastereomer δ = 170.2, 164.2, 136.4, 135.2, 131.4, 67.4, 60.8, 44.1, 42.4, 39.5, 38.7, 38.5, 21.6, 14.2. HRMS calcd for C14H18O3: m/z = 234.1256. Found: m/z = 234.1246.
(ii) Ru-catalyzed [2+2] cycloadditions between 1 and 2f (Table [1] , entry 9): A mixture of norbornene 1 (159 mg, 1.69 mmol), alkyne 2f (80 mg, 0.56 mmol), and THF (0.3 mL) in an oven-dried vial was added via a cannula to an oven-dried screw-cap vial containing Cp*RuCl(COD) (weighed out from a dry box, 13.3 mg, 0.035 mmol) under nitrogen. The oven-dried vial was rinsed with THF (0.3 mL). The reaction mixture was stirred in the dark at r.t. for 72 h. The crude product was purified by column chromatography (EtOAc:hexanes = 1:19) to give an inseparable mixture of cycloadducts 3f and 4f (111 mg, 0.474 mmol, 84%, dr = 5.2:1 measured by 1H NMR and GC) as a yellow oil.
Rf = 0.40 (EtOAc:hexanes = 1:4); GC (HP-1 column): retention time for major isomer = 17.23 min, retention time for minor isomer = 17.35 min. IR (CH2Cl2): 3391 (br m), 2958 (s), 2871 (m), 1740 (m), 1721 (s)1679 (s), 1037 (s)
cm-1. 1H NMR (400 MHz, CDCl3): δ = 5.15 (q, 0.2 H, J = 5.4 Hz), 5.09 (q, 0.8 H, J = 4.2 Hz), 4.44-4.50 (m, 1 H), 2.55 (br s, 1 H), 2.43 (m, 1 H), 2.16 (br s, 1 H), 2.12 (br s, 0.2 H), 2.02 (br s, 0.8 H), 1.57 (m, 2 H), 1.28-1.35 (m, 7 H), 1.01-1.09 (m, 3 H). 13C NMR (100 MHz, APT, CDCl3): major diastereomer δ = 168.0, 164.2, 129.0, 65.4, 60.7, 47.0, 45.5, 34.0, 33.4, 30.5, 28.0, 27.8, 21.3, 14.2; minor diastereomer
δ = 167.9, 164.2, 129.0, 67.1, 60.7, 47.6, 45.6, 34.1, 33.8, 30.4, 28.0, 21.7, 14.2. HRMS calcd for C14H20O3: m/z = 236.1412. Found: m/z = 236.1383.
(iii) Oxidation of the diastereomeric cycloadducts 3f/4f to the enantiomerically enriched product 11 (Scheme [2] ): To a solution of the diastereomeric cycloadducts 3f/4f (58.0 mg, 0.2455 mmol) in CH2Cl2 (1.5 mL) was added pyridinium dichromate (0.1402 g, 0.3727 mmol). The reaction was stirred at r.t. for 48 h. The amount of 2 mL of Et2O was then added, and the mixture was passed through a plug of silica gel. The solvent was evaporated and the product was purified by column chromatography (EtOAc:hexanes = 3:7) to give 11 (27.0 mg, 0.1154 mmol, 47%) as a colorless oil. Rf = 0.54 (EtOAc:hexanes = 3:7). [α]D 23 -17.8 (c 0.925, CHCl3, 62 ee% determined by HPLC). IR (CH2Cl2): 2960 (s), 2873 (s), 1716 (s), 1669 (s), 1615 (m), 1366 (m), 1260 (m) cm-1. HPLC (OJ-H column, 0.75 mL/min, 1% i-PrOH/Hexane, 254 nm): major enantiomer = 7.52 min; minor enantiomer = 8.01 min. 1H NMR (400 MHz, CDCl3): δ = 4.24 (q, 2 H, J = 7.1 Hz), 2.62 (s, 2 H), 2.48 (s, 3 H), 2.23 (br s, 2 H), 1.60 (m, 2 H), 1.32 (t, 3 H, J = 7.1 Hz), 1.23 (dm, 1 H, J = 10.7 Hz), 1.12 (m, 2 H), 1.04 (dm, 1 H, J = 10.7 Hz). 13C NMR (100 MHz, APT, CDCl3): δ = 195.4, 161.4, 149.9, 139.5, 60.8, 46.42, 46.36, 33.9, 33.8, 30.4, 29.5, 28.0, 27.9, 14.1. Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.98; H, 7.55.