A Novel One-Pot Iridium-Catalyzed Alder-Ene-Murahashi Sequence

Abstract

Yne allyl alcohols could be transformed under very mild conditions by a novel iridium-catalyzed one-pot cycloisomerization-Murahashi sequence in 43-77% yield.

Key words

additions - alkynes - catalysis - condensations - ene reactions - iridium

References and Notes

• For reviews, see:
• 2a Wasilke J. Obrey SJ. Baker RT. Bazan GC. Chem. Rev.  2005,  105:  1001 
• 2b Ajamian A. Gleason JL. Angew. Chem. Int. Ed.  2004,  43:  3754 
• 2c Lee JM. Na Y. Han H. Chang S. Chem. Soc. Rev.  2004,  33:  302 
• 3 For a review on sequentially Pd-catalyzed reactions, see: Müller TJJ. Top. Organomet. Chem.  2006,  19:  149 
• 4a For a review on sequentially Ru-catalyzed reactions, see: Bruneau C. Dérien S. Dixneuf PH. Top. Organomet. Chem.  2006,  19:  296 
• 4b For a highlight on sequentially Rh-catalyzed reactions, see: Körber N. Müller TJJ. Chim. Oggi  2006,  24:  22 
• For representative transition-metal-catalyzed Alder-ene reactions, see for example Pd:
• 5a Trost BM. Acc. Chem. Res.  1990,  23:  34 
• 5b Trost BM. Janssen Chim. Acta  1991,  9:  3 
• 5c Trost BM. Krische MJ. Synlett  1998,  1 
• Ru:
• 5d Trost BM. Chem. Ber.  1996,  129:  1313 
• 5e Trost BM. Toste FD. Tetrahedron Lett.  1999,  40:  7739 
• Rh:
• 5f Cao P. Wang B. Zhang X. J. Am. Chem. Soc.  2000,  122:  6490 
• 5g Cao P. Zhang X. Angew. Chem. Int. Ed.  2000,  22:  4104 
• 5h Lei A. He M. Zhang X. J. Am. Chem. Soc.  2002,  124:  8198 
• 5i Hashmi ASK. Haufe P. Rivas Nass A. Bats JW. Adv. Synth. Catal.  2004,  346:  421 
• 5j Hashmi ASK. Haufe P. Rivas Nass A. Adv. Synth. Catal.  2003,  345:  1237 
• 5k Hashmi ASK. Karch R. Rivas Nass A. Chem. Today  2006,  24:  16 ; supplement
• Ir:
• 5l Chatani N. Inoue H. Morimoto T. Muto T. Murai S. J. Org. Chem.  2001,  66:  4433 
• 5m Kezuka S. Okado T. Niou E. Takeuchi R. Org. Lett.  2005,  7:  1711 
• Ti:
• 5n Sturla SJ. Kablaoui NM. Buchwald SL. J. Am. Chem. Soc.  1999,  121:  1976 
• 6a Bartels B. Helmchen G. Chem. Commun.  1999,  8:  741 
• 6b Schelwies M. Dübon P. Helmchen G. Angew. Chem. Int. Ed.  2006,  45:  2466 
• 7 Murahashi S.-I. Takaya H. Acc. Chem. Res.  2000,  33:  1855 
• 8a Kressierer CJ. Müller TJJ. Synlett  2004,  655 
• 8b Kressierer CJ. Müller TJJ. Tetrahedron Lett.  2004,  45:  2155 
• 8c Kressierer CJ. Müller TJJ. Org. Lett.  2005,  7:  2237 
• 8d Kressierer CJ. Müller TJJ. Synlett  2005,  1721 

1

New address: Lehrstuhl für Organische Chemie, Institut für Organische Chemie und Makromolekulare Chemie der Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany

9

All compounds have been fully characterized by spectroscopic methods and by correct elemental analysis or HRMS.

10

Typical Procedure of Compound 2c (Table 1, Entry 6).
To a solution of 30 mg (44 µmol) of [IR (COD)Cl]₂ in 5 mL of anhyd THF were added 252 mg (1.02 mmol) of 1c. The reaction mixture was stirred at 60 °C for 24 h before it was diluted with Et₂O. After quick chromatography on dry silica gel, 179 mg (71%) of 2c were obtained as a yellow solid; mp 61-66 °C. R _f = 0.40 (n-hexane-Et₂O = 10:90, SiO₂). ¹H NMR (300 MHz, CDCl₃): δ = 2.79 (dd, J = 8.4, 18.4 Hz, 1 H), 2.91 (dd, J = 5.1, 18.4 Hz, 1 H), 3.42 (m, 1 H), 3.61 (dd, J = 5.6, 8.8 Hz, 1 H), 4.16 (dd, J = 6.7, 8.8 Hz, 1 H), 4.66 (s, 2 H), 6.46 (s, 1 H), 7.26 (d, J = 8.7 Hz, 2 H), 8.20 (d, J = 8.8 Hz, 2 H), 9.88 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 39.8 (CH), 47.3 (CH₂), 69.9 (CH₂), 72.4 (CH₂), 119.8 (CH), 123.9 (CH), 128.4 (CH), 143.2 (C_quat), 146.1 (C_quat), 149.3 (C_quat), 199.9 (CH). MS (EI, 70 eV): m/z (%) = 247 (24) [M]⁺, 230 (38) [M - OH]⁺, 229 (33) [M - H₂O]⁺, 204 (31) [M - C₂H₃O]⁺, 203 (64) [M - C₂H₄O]⁺, 158 (22) [M - C₄H₁₀O]⁺. HRMS (EI): m/z calcd: 247.0845; found: 247.0822. Anal. Calcd for C₁₃H₁₃O₄N (247.3): C, 63.15; H, 5.30; N 5.66. Found: C, 62.99; H, 5.39; N, 5.52.

11

CCDC-630817 (2c) and CCDC-630818 (4e) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone]; or [e-mail]].

12

Typical Procedure for 4e (Table 2, Entry 8).
To a solution of 30 mg (44 µmol) of [IR (COD)Cl]₂ in 2.5 mL of anhyd THF were added 360 mg (1.01 mmol) of 1e. The reaction mixture was stirred at r.t. for 24 h. Then 150 mg (1.51 mmol) of cyanoacetate were added and the reaction mixture was stirred for another 24 h at r.t. After dilution with Et₂O the crude product was chromatographed on silica gel to give 319 mg (0.73 mmol, 72%) of 4e as a white crystalline solid; mp 166-166.5 °C. R _f = 0.37 (n-hexane-Et₂O = 10:90, SiO₂). ¹H NMR (300 MHz, CDCl₃): δ = 2.42 (s, 3 H), 2.72 (m, 1 H), 2.85 (ddd, J = 6.1, 7.7, 13.9 Hz, 1 H), 2.99-3.11 (m, 2 H), 3.41 (ddd, J = 2.2, 8.2, 8.3 Hz, 1 H), 3.87 (s, 3 H), 4.23-4.05 (m, 2 H), 6.31 (s, 1 H), 7.14 (d, J = 8.4 Hz, 2 H), 7.43-7.21 (m, 5 H), 7.63 (dd, J = 7.9 Hz, 1 H), 7.72 (d, J = 8.3 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 21.5 (CH₃), 35.1 (CH₂), 43.4 (CH), 50.3 (CH₂), 51.6 (CH₂), 53.3 (CH₃), 111.4 (C_quat), 113.3 (C_quat), 124.8 (CH), 127.6 (CH), 127.7 (CH), 128.2 (CH), 128.7 (CH), 129.9 (CH), 132.5 (C_quat), 135.7 (C_quat), 137.6 (C_quat), 144.0 (C_quat), 159.4 (CH), 161.2 (C_quat.). MS (EI, 70 eV): m/z (%) = 436 (18) [M]⁺, 312 (54) [M - C₆H₆NO₂]⁺, 282 (25) [M -C₇H₆O₂S]⁺, 281 (100) [M - C₇H₇O₂S]⁺, 157 (25), 149 (25), 156 (60) [C₁₁H₁₀N]⁺, 91 (35) [C₇H₇]⁺. Anal. Calcd for C₂₄H₂₄O₄N₂S (436.5): C, 66.04; H, 5.54; N, 6.42. Found: C, 65.95; H, 5.66; N, 6.35.