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Synlett 2008(5): 759-764  
DOI: 10.1055/s-2008-1032111
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© Georg Thieme Verlag Stuttgart · New York

A Rh(I)-Catalyzed Cycloisomerization Reaction Affording Cyclic Trienones

Kay M. Brummond*, Daitao Chen, Thomas O. Painter, Shuli Mao, Darla D. Seifried
Department of Chemistry and University of Pittsburgh Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA 15260, USA
Fax: +1(412)6248611; e-Mail: kbrummon@pitt.edu;
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Publikationsverlauf

Received 4 December 2007
Publikationsdatum:
10. März 2008 (online)

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Abstract

A Rh(I)-catalyzed carbocyclization reaction of allene-ynones affords functionalized 2-alkylidene-3-vinylcyclohexenones and 2-alkylidene-3-vinylcyclopentenones. The scope, limitations, and utility of this triene-forming protocol have been examined and the results reported within.

Key words

allenes - alkynes - Rh(I) - cycloisomerization - triene

    References and Notes

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  • General Procedure for the Preparation of Allene-ynones 3
  • 7a

    In a manner entirely analogous to that reported by Trost:7b A solution of the alkyne (1.08 mmol) in THF (2.4 mL) was cooled to -78 °C and a solution of n-BuLi (0.6 mL of a 1.6 M solution in hexanes, 0.96 mmol) was added rapidly via syringe. After 5 min BF3·OEt2 (128 µL, 1.02 mmol) was added. The resultant solution/mixture was stirred for 15 min then a solution of the allenyl amide 1 (100 mg, 0.60 mmol) in THF (3 mL) was added via cannula. After 1.5 h, more BF3·OEt2 (128 µL, 1.02 mmol) and AcOH (58 µL, 1.02 mmol) were added. The reaction was allowed to warm to -20 °C and quenched with sat. aq NH4Cl (2.1 mL). After warming to r.t., the reaction mixture was diluted with Et2O and H2O. The layers were separated and the aqueous layer was extracted with Et2O (3×). The combined organic layers were washed with H2O (2×) and dried over MgSO4. This mixture was filtered through a pad of silica gel and concentrated under vacuum. The crude residue was purified by column chromatography on silica gel to give the product as a faint yellow to clear oil.
    Data for 3e: 1H NMR (300 MHz, CDCl3): δ = 5.06-4.98 (m, 1 H), 2.62 (dd, J = 6.7, 7.5 Hz, 2 H), 2.28-2.21 (m, 2 H), 1.66 (d, J = 2.7 Hz, 3 H), 1.57 (d, J = 7.0 Hz, 3 H), 0.21 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 201.6, 187.1, 101.9, 97.5, 97.1, 87.0, 43.0, 27.8, 19.3, 14.6, -0.9. IR (thin film): ν = 2962, 2900, 2151, 1967, 1679, 1252, 847 cm-1. MS: m/z
    (%) = 220 (16) [M+], 219 (6), 205 (8), 178 (12), 163 (29), 73 (100), 61 (100). HRMS (EI): m/z calcd for C13H20OSi [M+]: 220.1283; found: 220.1289.
    Data for 3h: 1H NMR (300 MHz, CDCl3): δ = 7.54 (d, J = 8.9 Hz, 2 H), 6.90 (d, J = 8.9 Hz, 2 H), 5.11-5.04 (m, 1 H), 3.85 (s, 3 H) 2.76 (dd, J = 6.8, 8.1 Hz, 2 H), 2.39-2.31 (m, 2 H), 1.73 (d, J = 2.8 Hz, 3 H), 1.62 (d, J = 6.9 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 201.7, 187.2, 161.5, 134.9, 114.2, 111.8, 97.6, 91.4, 87.6, 86.8, 55.2, 43.2, 28.1, 19.3, 14.6. IR (thin film): ν = 2979, 2899, 2849, 2553, 2197, 1965, 1665, 1254, 1092 cm-1. MS: m/z (%) = 254 (27) [M+], 253 (16), 239 (40), 237 (53), 211 (54), 197 (54), 165 (47), 159 (100), 144 (44), 116 (47), 77 (47). HRMS (EI): m/z calcd for C17H18O2 [M+]: 254.1307; found: 254.1282.
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  • 17 With the exception of 12b, which had to be stored in benzene at -20 °C, the only literature report on the formation of five-membered cross-conjugated triene stressed product instability. For details, see: Yamazaki T. Urabe H. Sato F. Tetrahedron Lett.  1998,  39:  7333 
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8

We have seen similarly facile reactions when the cycloisomerization substrate possesses an aminoester tether. See ref. 2c.

11

General Procedure for the Preparation of Trienone 4 A 2-dram vial, equipped with a stir bar was charged with allene-ynone 3 (0.1 mmol) and toluene (0.33 mL), sealed with a septum, and degassed (degassing was accomplished by bubbling argon through the stirred solution for 20 min). Rhodium biscarbonyl chloride dimer {[Rh(CO)2Cl]2, 3 mol%} was then added and the reaction progress was monitored by TLC. Upon completion of the reaction, the mixture was diluted with a 10% EtOAc-hexanes solution and filtered through a pad of silica gel, further eluting with 10% EtOAc-hexanes solution. The resultant yellow solution was concentrated under vacuum to yield the products as yellow oils without further purification.
Data for 4e: 1H NMR (300 MHz, CDCl3): δ = 6.27 (dd, J = 11.3, 17.7 Hz, 1 H), 6.01 (s, 1 H), 5.45 (dd, J = 2.1, 11.3 Hz, 1 H), 5.15 (dd, J = 2.1, 17.7 Hz, 1 H), 2.61-2.51 (m, 4 H), 1.95 (s, 3 H), 0.13 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 200.6, 145.6, 139.1, 135.3, 134.0, 133.7, 119.8, 37.8, 30.8, 21.8, -0.2. IR (thin film): ν = 2945, 1701, 1542, 1245, 856 cm-1. MS: m/z (%) = 220 (1) [M+], 205 (40), 75 (13). HRMS (EI): m/z calcd for C13H20OSi [M+]: 220.1283; found: 220.1281.
Data for 4h: 1H NMR (300 MHz, CDCl3): δ = 7.44 (d, J = 8.7 Hz, 2 H), 6.83 (d, J = 8.8 Hz, 2 H), 6.61(s, 1 H), 6.34 (dd, J = 11.2, 17.7, 1 H), 5.49 (dd, J = 2.1, 11.2 Hz, 1 H), 5.27 (dd, J = 2.1, 17.8 Hz, 1 H), 3.81 (s, 3 H), 2.71-2.59 (m, 4 H), 1.94 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 202.6, 159.5, 133.7, 133.6, 132.7, 132.5, 131.3, 128.4, 119.7, 113.3, 55.1, 39.6, 32.3, 21.1. IR (thin film): ν = 3081, 2908, 2836, 1698, 1603, 1509, 1254, 1032, 829 cm-1. MS: m/z (%) = 277 (32) [M + 23Na+], 255 (17). ES-HRMS: m/z calcd for C17H18O2 [M + 23Na+]: 277.1204; found: 277.1215.

12

Preparation of 6,7,8,10a-Tetrahydro-2-methyl-1-vinyl-5 H -xanthene (7)
Following the general procedure for the preparation of trienone 4: toluene (2.8 mL), allene-ynone 3f (32 mg, 0.140 mmol), [Rh(CO2)Cl]2 (1.6 mg, 0.004 mmol, 5 mol%), purification by silica gel column chromatography eluting with 2% EtOAc-hexanes (column pretreated with a 1% solution of Et3N in hexanes) to afford 7 as a green solid (9 mg, 29%). 1H NMR (300 MHz, CDCl3): δ = 6.85 (d, J = 8.1 Hz, 1 H), 6.63 (dd, J = 11.4, 17.8 Hz, 1 H), 6.56 (d, J = 8.1 Hz, 1 H), 6.39 (s, 1 H), 5.58 (dd, J = 2.0, 11.4 Hz, 1 H), 5.23 (dd, J = 2.0, 17.8 Hz, 1 H), 4.86 (dd, J = 5.7, 10.9 Hz, 1 H), 2.60-1.19 (m, 8 H), 2.18 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 151.3, 137.5, 134.4, 133.7, 128.8, 127.8, 120.4, 119.1, 114.9, 113.5, 76.1, 34.7, 33.2, 26.5, 24.2, 19.8. IR (thin film): ν = 3078, 3058, 2932, 2857, 1582, 1468, 1235, 1041, 811 cm-1. MS: m/z (%) = 226 (100) [M+], 225 (90), 223 (82), 198 (61), 197 (60), 145 (43), 128 (44), 115 (60). HRMS (EI): m/z calcd for C16H18O [M+]: 226.1358; found: 226.1353.

13

Preparation of Allenyl Alkynone 9e
A flame-dried 100 mL round-bottomed flask was charged with 2,2-diethylhexa-3,4-dienal (8b, 1.52 g, 10.0 mmol) and THF (40 mL). After cooling to 0 °C, 1-propynylmagnesium bromide (24 mL, 0.5 M in THF, 12 mmol) was slowly added via syringe and the mixture was stirred at 0 °C for 2 h. The reaction mixture was quenched with sat. NH4Cl (20 mL). The mixture was partitioned between Et2O (30 mL) and H2O (30 mL). The layers were separated and the aqueous phase was extracted with Et2O (2 × 30 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure to afford a light yellow oil (1.65 g). A portion of the oil (452 mg) was transferred into a 50 mL round-bottomed flask fitted with a Teflon-coated stirring bar and dissolved in acetone (20 mL). After cooling to 0 °C, freshly prepared Jones reagent was added dropwise via a pipette until an orange color persisted. The reaction mixture was then poured into Et2O (20 mL) and H2O (10 mL). The layers were separated and the aqueous phase was extracted with Et2O (2 × 20 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure. Purification of the yellow oil by flash chromatography (10% EtOAc-hexanes) afforded the title compound 9e (425 mg, 79%) as a light yellow oil. 1H NMR (300 MHz, CDCl3): δ = 5.28-5.19 (m, 2 H), 2.04 (s, 3 H), 1.78-1.70 (m, 4 H),1.68 (dd, J = 6.6, 3.6 Hz, 3 H), 0.83 (t, J = 7.4 Hz, 3 H), 0.82 (t, J = 7.4 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 205.1, 191.4, 92.4, 90.6, 88.2, 78.8, 56.5, 27.5, 14.1, 8.5, 4.1. IR (thin film): ν = 2968, 2938, 2218, 1963, 1666 cm-1. MS: m/z (%) = 190 (15) [M+], 175 (28), 161 (95), 147 (65), 81 (100). HRMS: m/z calcd for C13H18O [M+]: 190.1357; found: 190.1358.

16

Preparation of Allenyl Alkynone 11b A flame-dried 25 mL round-bottomed flask was charged with N-[2-(N-methoxy-N-methylcarbamoyl)hexa-3,4-dien-2-yl]benzamide (268 mg, 0.93 mmol) and THF (15 mL). After cooling to 0 °C, 1-propynylmagnesium bromide (4.4 mL, 0.5 M in THF, 2.2 mmol) was slowly added via syringe and the mixture was stirred at 0 °C for 3 h. The reaction mixture was quenched with sat. NH4Cl (10 mL). The mixture was partitioned between Et2O (15 mL) and H2O (15 mL). The layers were separated and the aqueous phase was extracted with Et2O (2 × 15 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure to afford a white solid. The solid was purified via silica gel column chromatography (50% EtOAc-hexanes) to give the title compound 11b (242 mg, 97%) as a white solid. 1H NMR (300 MHz, CDCl3): δ = 7.81-7.78 (m, 2 H), 7.54-7.41 (m, 3 H), 7.21 (br s, 0.3 H),* 7.11 (br s, 0.7 H), 5.24 (p, J = 7.1 Hz, 1 H), 5.40-5.32 (m, 1 H), 2.02 (s, 1 H),* 1.99 (s, 2 H), 1.81 (s, 1 H),* 1.78 (s, 2 H), 1.74 (dd, J = 7.0, 3.2 Hz, 2 H), 1.72 (dd, J = 7.0, 3.2 Hz, 1 H)*. 13C NMR (75 MHz, CDCl3): δ = 204.4, 204.2,* 185.9, 166.6, 165.3,* 134.7, 134.6,* 131.8, 131.7,* 128.8, 127.1, 93.8,* 93.6, 93.5,* 93.0, 91.9, 91.7,* 77.4,* 77.3, 63.7,* 63.5, 21.9, 14.1,* 14.0, 4.50,* 4.42. IR (thin film): ν = 3280, 2211, 1966, 1688, 1627 cm-1. MS: m/z (%) = 267 (10) [M+], 253 (28), 105 (100), 77 (65). HRMS: m/z calcd for C17H17NO2 [M+]: 267.1259; found: 267.1263. *Denotes the minor diastereomer.

18

General Procedure for the Preparation of Trienones 12 A flame-dried test tube equipped with a Teflon-coated stir bar was charged with allene-ynone 9 or 11 (1.0 mmol, 1 equiv) and toluene (10 mL) under an atmosphere of N2. After adding [Rh(CO)2Cl]2 (0.05 mmol, 0.05 equiv), the reaction mixture was stirred at r.t. until complete consumption of starting material (as observed by TLC). The solution was concentrated under reduced pressure and the residue was purified via silica gel column chromatography (10% EtOAc-hexanes) to afford trienone 12.
Data for 12a: 1H NMR (300 MHz, CDCl3): δ = 6.44 (dd, J = 17.6, 11.1 Hz, 1 H), 6.16 (t, J = 7.4 Hz, 1 H), 6.12 (s, 1 H), 5.62 (dd, J = 17.6, 1.6 Hz, 1 H), 5.28 (dd, J = 11.1 1.6 Hz, 1 H), 2.78 (q, J = 7.5 Hz, 2 H), 1.45-1.36 (m, 4 H), 1.12 (s, 6 H), 0.92 (t, J = 6.9 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 210.8, 139.5, 137.5, 136.2, 134.9, 129.8, 116.8, 48.3, 31.7, 27.2, 23.6, 22.5, 13.9. IR (thin film): ν = 2959, 2932, 2871, 1708 cm-1. MS: m/z (%) = 204 (43) [M+], 189 (15), 175 (25), 119 (88), 91 (100). HRMS: m/z calcd for C14H20O [M+]: 204.1514; found: 204.1514.
Data for 12c: 1H NMR (300 MHz, CDCl3): δ = 7.94 (dd, J = 7.8, 2.1 Hz, 2 H), 7.43-7.32 (m, 3 H), 6.85 (s, 1 H), 6.56 (ddd, J = 17.4, 11.1, 1.2 Hz, 1 H), 6.29 (s, 1 H), 5.74 (dd, J = 17.4, 1.5 Hz, 1 H), 5.38 (dd, J = 11.1, 1.5 Hz, 1 H), 1.20 (s, 6 H). 13C NMR (75 MHz, CDCl3): δ = 208.6, 141.7, 137.8, 135.2, 134.8, 133.0, 131.1, 130.5, 130.0, 129.6, 128.2, 117.9, 48.6, 24.0. IR (thin film): ν = 2942, 1708 cm-1. MS: m/z (%) = 224 (40) [M+], 196 (50), 181 (65), 129 (100). HRMS (EI): m/z calcd for C16H16O [M+]: 224.1201; found: 224.1198.
Data for 12e: 1H NMR (300 MHz, CDCl3): δ = 6.44 (ddd, J = 17.6, 11.2, 0.9 Hz, 1 H), 6.19 (dq, J = 7.6, 0.7 Hz, 1 H), 6.04 (s, 1 H), 5.63 (dd, J = 17.6, 1.6 Hz, 1 H), 5.27 (dd, J = 11.2, 1.6 Hz, 1 H), 2.25 (dd, J = 7.6, 0.7 Hz, 3 H), 1.66 (dq, J = 13.6, 7.5 Hz, 2 H), 1.50 (dq, J = 13.6, 7.5 Hz, 2 H), 0.74 (t, J = 7.5 Hz, 6 H). 13C NMR (75 MHz, CDCl3): δ = 212.1, 142.4, 137.9, 133.2, 130.5, 129.9, 116.7, 57.3, 29.6, 14.1, 9.3. IR (thin film): ν = 2963, 2929, 1720 cm-1. MS: m/z (%) = 190 (54) [M+], 161 (80), 133 (86), 84 (100). HRMS (EI): m/z calcd for C13H18O [M+]: 190.1357; found: 190.1355.

19

The stereochemistry has been assigned based upon X-ray crystal data of a similar compound. This information will be published in the near future.

20

Preparation of N -{(1 Z ,3a S ,8 S ,8a R ,8b R )-6-Ethylidene-1,2,3,3a,4,6,7,8,8a,8b-decahydro-8-methyl-1,3,7-trioxo-2-phenylcyclopenta[ e ]isoindol-8-yl}benzamide (13)
A flame-dried test tube equipped with a Teflon-coated stirring bar was charged with N-[(13Z)-4-ethylidene-1-methyl-5-oxo-3-vinylcyclopent-2-enyl]benzamide (12h, 100 mg, 0.37 mmol) and 1-phenyl-1H-pyrrole-2,5-dione (68 mg, 0.39 mmol). After adding toluene (4 mL), the test tube was placed into a preheated 80 °C oil bath until complete consumption of starting materials (as observed by TLC). The solution was directly purified via silica gel column chromatography (50% EtOAc-hexanes) to afford the title compound 13 (87.4 mg, 54%). 1H NMR (300 MHz, CDCl3): δ = 7.89-7.85 (m, 2 H), 7.54-7.30 (m, 7 H), 7.06-7.03 (m, 2 H), 6.70 (q, J = 7.6 Hz, 1 H), 6.19-6.11 (m, 1 H), 3.58 (dd, J = 8.3, 4.3 Hz, 1 H), 3.40 (t, J = 8.3 Hz, 1 H), 3.26-3.22 (m, 1 H), 2.92 (dd, J = 7.5 and 1.0 Hz, 1 H), 2.57-2.47 (m, 1 H), 2.30 (d, J = 7.6 Hz, 3 H), 1.74 (s, 3 H). 13C NMR (75 MHz, CD2Cl2): δ = 204.1, 178.7, 177.5, 167.3, 140.5, 137.1, 135.1, 132.3, 131.9, 131.1, 129.3, 128.9, 128.6, 127.4, 126.9, 116.8, 63.3, 46.4, 43.6, 41.7, 27.0, 25.9, 15.1. IR (thin film): ν = 3425, 2975, 1773, 1708, 1654, 1522 cm-1. MS: m/z
(%) = 441 (100) [M+ + 1], 308 (38). HRMS (EI): m/z calcd for C27H25N2O4 [M+]: 441.1814; found: 441.1812.

22

Preparation of Adduct 15
To a refluxing solution of (5Z)-2,2-diethyl-5-ethylidene-4-vinylcyclopent-3-enone (12e, 28 mg, 0.15 mmol) and Rh(OAc)2 (3.3 mg, 0.0075 mmol) in CH2Cl2 (1.5 mL) was added a CH2Cl2 (1 mL) solution of diethyl 4-diazo-2-pentenedioate (48 mg, 0.23 mmol) over 10 min under argon. After 30 min, TLC showed complete consumption of 12e. The solvent was removed and the crude mixture was purified via silica gel flash chromatography (10% EtOAc-hexanes) to give 14 (26 mg, 47%) together with the trans-divinylcyclopropane (cis/trans = 7:1). A test tube was charged with 14 (19 mg, 0.051 mmol) and maleic anhydride (7.5 mg, 0.077 mmol) and purged with N2 for 5 min. Toluene (0.8 mL) was added and the test tube was placed into a preheated oil bath (80 °C). After 3 h, the reaction mixture was cooled to r.t. and directly applied to silica gel flash chromatography (35% EtOAc-hexanes) to give 15 (14 mg, 60%) as a single diastereomer. 1H NMR (300 MHz, CDCl3): δ = 7.04 (dd, J = 7.2, 2.1 Hz, 1 H), 4.30-4.22 (m, 2 H), 4.12-4.00 (m, 2 H), 3.81 (dd, J = 7.1, 2.8 Hz, 1 H), 3.60-3.57 (m, 1 H), 3.51 (q, J = 7.3 Hz, 1 H), 3.29-3.25 (m, 2 H), 3.12 (t, J = 2.7 Hz, 1 H), 2.94-2.88 (m, 1 H), 1.69-1.62 (m, 2 H), 1.54-1.52 (m, 1 H), 1.48 (q, J = 7.4 Hz, 4 H), 1.39-1.27 (m, 2 H), 1.34 (t, J = 7.1 Hz, 3 H), 1.01 (t, J = 7.4 Hz, 3 H), 0.91-0.84 (m, 2 H), 0.73 (t, J = 7.4 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 208.1, 171.0, 170.8, 170.6, 170.2, 167.4, 137.5, 136.6, 134.9, 61.9, 53.3, 49.8, 46.9, 46.3, 45.2, 36.7, 31.8, 29.6, 27.7, 27.4, 22.9, 21.8, 14.7, 14.5, 14.1, 8.8, 8.6. IR (thin film): ν = 2969, 2937, 1781, 1699, 1461 cm-1. MS: m/z (%) = 472 (100) [M+], 426 (71), 398 (84). HRMS (EI): m/z calcd for C26H32O8 [M+]: 472.2097; found: 472.2101.