Tandem Catalysis: A Ring-Closing Metathesis Followed by Dehydrogenative Oxidation to Afford Substituted Indenones

Abstract

Grubbs second generation catalyst converts substituted 1-(2-propenylphenyl)prop-2-en-1-ols into substituted indenols or indenones depending on the reaction conditions employed. The formation of indenones represents the first example of a tandem ruthenium-mediated ring-closing metathesis-dehydrogenative oxidation reaction.

metathesis - ruthenium - dehydrogenations - tandem ­reactions - indenols - indenones

References

1a Deiters A. Martin SF. Chem. Rev.  2004,  104:  2199 

1b McReynolds MD. Dougherty JM. Hanson PR. Chem. Rev.  2004,  104:  2239 , and reviews cited therein

2 Alcaide B. Almendros P. Chem.-Eur. J.  2003,  9:  1259 

3 Schmidt B. Eur. J. Org. Chem.  2004,  1865 

4a Fürstner A. Thiel OR. Ackermann L. Schanz H.-J. Nolan SP. J. Org. Chem.  2000,  65:  2204 

4b Kinderman SS. Doodeman R. van Beijma JW. Russcher JC. Tjen KCMF. Kooistra TM. Mohaselzadeh H. van Maarseveen JH. Hiemstra H. Schoemaker HE. Rutjes FPJT. Adv. Synth. Catal.  2002,  344:  736 

4c Sutton AE. Seigal BA. Finnegan DF. Snapper ML. J. Am. Chem. Soc.  2002,  124:  13390 

4d De Clercq B. Verpoort F. J. Organomet. Chem.  2003,  672:  11 

4e Louie J. Bielawski CW. Grubbs RH. J. Am. Chem. Soc.  2001,  123:  11312 

4f Schmidt B. Pohler M. Org. Biomol. Chem.  2003,  1:  2512 

4g van Otterlo WAL. Ngidi EL. Coyanis EM. de Koning CB. Tetrahedron Lett.  2003,  44:  311 

4h Fogg DE. Amoroso D. Drouin SD. Snelgrove J. Conrad J. Zamanian F. J. Mol. Catal. A: Chem.  2002,  190:  177 

4i Moreno-Mañas M. Pleixats R. Santamaria A. Synlett  2001,  1784 

4j Schmidt B. Chem. Commun.  2004,  742 

4k Rosillo M. Casarrubios L. Domínguez G. Pérez-Castells J. Org. Biomol. Chem.  2003,  1:  1450 

5a van Otterlo WAL. Ngidi EL. de Koning CB. Tetrahedron Lett.  2003,  44:  6483 

5b van Otterlo WAL. Pathak R. de Koning CB. Synlett  2003,  1859 

5c van Otterlo WAL. Ngidi EL. de Koning CB. Fernandes MA. Tetrahedron Lett.  2004,  45:  659 

6a Coombs MM. Benzocyclopropene, Benzocyclobutene and Indene, and their Derivatives, In Rodd’s Chemistry of Carbon Compounds   2nd ed., 2nd Suppl., Vol. IIIF(partial)/IIIG/IIIH:  Sainsbury M. Elsevier; Amsterdam: 1995. 

6b Ivchenko NB. Ivchenko PV. Nifant’ev IE. Russ. J. Org. Chem.  2000,  36:  609 

7 Ishiguru Y. Okamoto K. Ojima F. Sonoda Y. Chem. Lett.  1993,  1139 

8 Sengupta P. Sen M. Niyogi SK. Pakrashi SC. Ali E. Phytochemistry  1976,  15:  995 

9 Harrowven DC. Newman NA. Knight CA. Tetrahedron Lett.  1998,  39:  6757 

10a Chang K.-J. Rayabarapu DK. Cheng C.-H. J. Org. Chem.  2004,  69:  4781 

10b Quan LG. Gevorgyan V. Yamamoto Y. J. Am. Chem. Soc.  1999,  121:  3545 

10c Gevorgyan V. Quan LG. Yamamoto Y. Tetrahedron Lett.  1999,  40:  4089 

10d Vicente J. Abad J.-A. Gil-Rubio J. Organometallics  1996,  15:  3509 

11a Pletnev AA. Tian Q. Larock RC. J. Org. Chem.  2002,  67:  9276 

11b Padwa A. Molecules  2001,  6:  1 

11c Fukuyama T. Chatani N. Kakiuchi F. Murai S. J. Org. Chem.  1997,  62:  5647 

12 For a recently reported route to an indenol using a RCM approach see: Clive DLJ. Yu M. Sannigrahi M. J. Org. Chem.  2004,  69:  4116 

13

Work taken from the post-doctoral research project of Dr. E. M. Coyanis and the ongoing MSc project of Ms J.-L. Panayides.

14 de Koning CB. Michael JP. Rousseau AL. J. Chem. Soc., Perkin Trans. 1  2000,  787 

15 Krompiec S. KuŸnik N. Penczek R. Rzepa J. Mrowiec-Bialoñ J. J. Mol. Catal. A: Chem.  2004,  219:  29 ; and citations therein

16a Huang K.-S. Wang E.-C. Tetrahedron Lett.  2001,  42:  6155 

16b de Koning CB. Giles RGF. Green IR. Jahed NM. Tetrahedron  2003,  59:  3175 

17

Typical Experimental Procedure for Forming Indenols:
Grubbs catalyst 1 (5 mol%) was added to a degassed solution (N₂) of 5a (262 mg, 0.62 mmol) in CH₂Cl₂ (25 mL). The solution was then stirred under N₂ at r.t. for 3 h. After evaporation of the solvent and column chromatographic purification of the residue (5-10% EtOAc-hexane), 4-isopropoxy-5-methoxy-1H-inden-1-ol (6a) was obtained as a pale yellow oil (191 mg, 87%). ¹H NMR (200 MHz, CDCl₃, assignments with the same superscript may be interchanged): δ = 7.12 (d, 1 H, J = 7.9 Hz, 7-H), 6.73 (d, 1 H, J = 5.6 Hz, 3-H), 6.66 (d, 1 H, J = 7.9 Hz, 2-H), 6.27 (dd, 1 H, J = 5.6 and 2.0 Hz, 6-H), 5.04 (br s, 1 H, 1-H), 4.33 [br sept, 1 H, J = 6.2 Hz, CH(CH₃)₂], 3.80 (s, 3 H, OCH₃), 2.08 (br s, 1 H, OH), 1.28 [d, 3 H, J = 6.4 Hz, CH(CH ₃)CH₃], 1.25 [d, 3 H, J = 6.5 Hz, CH(CH₃)CH ₃]. ¹³C NMR (50 MHz, CDCl₃): δ = 153.3 (C), 140.1 (C), 138.4 (C), 137.8 (CH), 136.7 (C), 129.2 (CH), 118.9 (CH), 109.4 (CH), 77.1 (OCH), 75.6 (C-O), 55.9 (OCH₃), 22.5 (CH₃), 22.4 (CH₃).
IR: 3400(br), 1674, 1617, 1596, 1556 cm^-1. HRMS (CI): m/z calcd for C₁₃H₁₆O₃: 220.10995; found: 220.10990. MS: m/z (%) = 220 (69) [M ⁺ ], 179 (18), 178 (100), 177 (28), 176 (16), 163 (41), 161 (12), 149 (16), 147 (18), 146 (18), 135 (10), 118 (10), 77 (10), 69 (11), 57 (14), 55 (12), 43 (28), 41 (19).

18

All new compounds were identified using routine spectroscopy and gave satisfactory data.

19

In an attempt to improve the yields of indenols 6d and 6e we protected the alcohol functionalities of 5d and 5e with acetyl groups. However, much to our surprise, the RCM reactions of these substrates, at r.t. or at 110 °C, did not proceed to afford the acetyl-protected cyclic products and only starting material was recovered.

20

Typical Experimental Procedure for Forming Indenones:
Grubbs catalyst 1 (8 mol%) was added to a degassed solution (N₂) of 5a (141 mg, 0.54 mmol) in toluene (10 mL). The solution was then heated at 80 °C under N₂ for 2 h. Evaporation of the solvent and column chromatographic purification of the residue (20% EtOAc-hexane) then afforded 4-isopropoxy-5-methoxyinden-1-one (7a) as a yellow semi-solid (72 mg, 62%). ¹H NMR (200 MHz, CDCl₃): δ = 7.64 (d, 1 H, J = 5.8 Hz, H-3), 7.38 (d, 1 H, J = 7.8 Hz, H-7), 6.60 (d, 1 H, J = 7.8 Hz, H-6), 5.86 (d, 1 H, J = 5.8 Hz, H-2), 4.40 [sept, 1 H, J = 6.1 Hz, CH(CH₃)₂], 3.87 (s, 3 H, OCH₃), 1.31 [d, 6 H, J = 6.1 Hz, CH(CH ₃)₂]. ¹³C NMR (50 MHz, CDCl₃): δ = 197.2 (C=O), 158.8 (C), 145.5 (CH), 142.0 (C), 137.5 (C), 127.9 (CH), 123.9 (C), 119.7 (CH), 109.8 (CH), 75.9 (OCH), 56.1 (OCH₃), 22.4 (CH₃). IR: 1708, 1604 cm^-1. HRMS (CI): m/z calcd for C₁₃H₁₄O₃: 218.09430; found: 218.09433. MS: m/z (%) = 218 (29) [M ⁺ ], 193 (21), 178 (20), 177 (40), 176 (100), 175 (25), 163 (17), 161 (23), 149 (37), 147 (20), 105 (21), 91 (17), 77 (26), 73 (23), 69 (22), 57 (33), 55 (26), 43 (49), 41 (46).

21

X-ray crystal structure of 4-isopropoxy-5-methoxy-2-methyl-3-phenylinden-1-one (7f): crystallized from CHCl₃, formula: C₂₀H₂₀O₃, M = 308.36, color of crystal: yellow, prism, crystal size 0.31 × 0.20 × 0.02 mm, a = 6.3298 (11) Å, b = 18.133 (3) Å, c = 7.7645 (13) Å, β = 110.094 (3)°, V = 836.9 (2) ų, ρ_calc = 1.224 Mg/m³, µ = 0.081 mm^-1, F(000) = 328, Z = 2, monoclinic, space group P2₁, T = 293 K, 5132 reflections collected, 2444 independent reflections, θ_max = 26.50°, 212 refined parameters, maximum residual electron density 0.129 and -0.161 e·Å^-3. R1 = 0.0421, wR2 = 0.0813. Crystallographic data for the structure have been deposited with the Cambridge Crystallographic Data Centre as deposition No. CCDC-250072.

22 Storage of the indenols (as oils) without the exclusion of air resulted in a slow conversion into indenones (ca. 5% over six months)

A literature search also revealed that mild oxidants such a MnO₂,^23a chromium(III)(salen) with PhI(OAc)₂ ^23b or PhIO^23c have been successfully used to accomplish the indenol to indenone transformation. See

23a Wu Y. Ahlberg P. Acta Chem. Scand.  1995,  49:  364 

23b Adam W. Hajra S. Herderich M. Saha-Möller CR. Org. Lett.  2000,  2:  2773 

23c Adam W. Gadissa Gelalcha F. Saha-Möller CR. Stegmann VR. J. Org. Chem.  2000,  65:  1915 

24a Cho JH. Kim BM. Org. Lett.  2003,  5:  531 

24b Mi Ahn Y. Yang K. Georg GI. Org. Lett.  2001,  3:  1411 

25a Westhus M. Gonthier E. Brohm D. Breinbauer R. Tetrahedron Lett.  2004,  45:  3141 

25b Gonthier E. Breinbauer R. Synlett  2003,  1049 

When a NMR spectroscopically monitored experiment (d ₈-toluene) was conducted on 5a (with catalyst 1) at 105 °C, evidence suggested that a ruthenium-promoted redox isomerization was occurring to form the corresponding indanone 8. See the following references describing this type of transformation mediated by ruthenium metathesis catalysts:

26a Greenwood ES. Parsons PJ. Young MJ. Synth. Commun.  2003,  33:  223 

26b Gurjar MK. Yakambram P. Tetrahedron Lett.  2001,  42:  3633 

26c Trost BM. Kulawiec RJ. J. Am. Chem. Soc.  1993,  115:  2027 . Repeating the experiment in a conventional manner on substrate 5a [toluene, catalyst 1 (5%), r.t., 24 h, then ca. 100 °C, 18 h] gave the indanone 8 in an unoptimized yield of 51%; its structure was confirmed by various spectroscopic techniques. To the best of our knowledge this constitutes the first report of a tandem RCM-redox isomerization reaction and we will be investigating reactions of this type in more detail. 4-Isopropoxy-5-methoxyindan-1-one (8): ¹H NMR (200 MHz, CDCl₃): δ = 7.48 (d, 1 H, J = 8.3 Hz, 7-H), 6.95 (d, 1 H, J = 8.3 Hz, 6-H), 4.51 [sept, 1 H, J = 6.1 Hz, CH(CH₃)₂], 3.90 (s, 3 H, OCH₃), 3.08-3.02 (m, 2 H, 2-H), 2.66-2.60 (m, 2 H, 3-H), 1.29 [d, 6 H, J = 6.1 Hz, CH(CH ₃)₂]. ¹³C NMR (50 MHz, CDCl₃): δ = 205.6 (C=O), 157.6 (C), 149.0 (C), 143.4 (C), 131.0 (C), 119.7 (CH), 112.1 (CH), 74.6 (OCH), 56.1 (OCH₃), 36.4 (C-2), 22.9 (C-3), 22.7 (CH₃). IR: 1708, 1598 cm^-1. HRMS (CI): m/z calcd for C₁₃H₁₆O₃: 220.10995; found: 220.10989. MS: m/z (%) = 220 (33) [M ⁺ ], 178 (100), 163 (8), 150 (6), 149 (6), 135 (15), 107 (10)

27a Meijer RH. Ligthart GBWL. Meuldijk J. Vekemans JAJM. Hulshof LA. Mills AM. Kooijman H. Spek AL. Tetrahedron  2004,  60:  1065 

27b Ligthart GBWL. Meijer RH. Donners MPJ. Meuldijk J. Vekemans JAJM. Hulshof LA. Tetrahedron Lett.  2003,  44:  1507 

27c Choi JH. Kim N. Shin YJ. Park JH. Park J. Tetrahedron Lett.  2004,  45:  4607