Copper(I) Iodide Catalyzed
Domino Knoevenagel Hetero-Diels-Alder Reaction
of Terminal Acetylenes: Synthesis of Pyrano[2,3-c]pyrazoles

Malihe Javan Khoshkholgh; Saeed Balalaie; Hamid Reza Bijanzadeh; Jürgen H. Gross

doi:10.1055/s-0028-1087380

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Synlett 2009(1): 55-58
DOI: 10.1055/s-0028-1087380

LETTER

Copper(I) Iodide Catalyzed Domino Knoevenagel Hetero-Diels-Alder Reaction of Terminal Acetylenes: Synthesis of Pyrano[2,3-c]pyrazoles

Malihe Javan Khoshkholgh^a, Saeed Balalaie*^a, Hamid Reza Bijanzadeh^b, Jürgen H. Gross^c
^a Department of Chemistry, K. N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran
Fax: +98(21)22853650; e-Mail: balalaie@kntu.ac.ir; e-Mail: balalaie@yahoo.com;
^b Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran 18716, Iran
^c Organisch-Chemisches Institut, Universitaet Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany

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Publication History

Received 25 September 2008
Publication Date:
12 December 2008 (online)

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Abstract

A new and efficient CuI-catalyzed domino Knoevenagel hetero-Diels-Alder reaction of 1-oxa-1,3-butadienes with terminal unactivated acetylenes as building blocks to afford pyrano[2,3-c]pyrazoles has been developed. The products were obtained in good to high yields in most cases. Synthesis of polycyclic compounds in one-pot, with easy workup, and mild reaction conditions are advantages of our reported method.

Key words

domino Reaction - hetero-Diels-Alder reaction - Knoe-venagel condensation - cuprous iodide - alkynes - pyran

References and Notes

1a Liu Y. Song F. Song Z. Liu M. Yan B. Org. Lett. 2005, 7: 5409

Search in Google Scholar
1b Bruneau C. Angew. Chem. Int. Ed. 2005, 44: 2328

Search in Google Scholar
1c Asao N. Sato K. Yamamoto Y. J. Org. Chem. 2005, 70: 3682

Search in Google Scholar
1d Asao N. Takashi K. Lee S. Kasahara T. Yamamoto Y. J. Am. Chem. Soc. 2002, 124: 12650

Search in Google Scholar
1e Shibata T. Ueno Y. Kanda K. Synlett 2006, 411
1f Asao N. Yudha S. Nogami T. Yamamoto Y. Angew. Chem. Int. Ed. 2005, 44: 5526

Search in Google Scholar
2a Yi CS. Yun SY. J. Am. Chem. Soc. 2005, 127: 1700

Search in Google Scholar
2b Ermolat’ev DS. Mehta VP. Eycken EV. Synlett 2007, 3117
2c Godet T. Vaxelaie C. Michel C. Milet A. Belmont P. Chem. Eur. J. 2007, 13: 5632

Search in Google Scholar
2d Xiao Y. Zhang J. Angew. Chem. Int. Ed. 2008, 47: 1903

Search in Google Scholar
2e Leogane O. Lebel H. Angew. Chem. Int. Ed. 2008, 47: 350

Search in Google Scholar
3a Asao N. Kasahara T. Yamamoto Y. Angew. Chem. Int. Ed. 2003, 42: 3504

Search in Google Scholar
3b Patil NT. Wu H. Yamamoto Y. J. Org. Chem. 2005, 70: 4531

Search in Google Scholar
3c Bertrand P. Gesson JP. J. Org. Chem. 2007, 72: 3596

Search in Google Scholar
4a Patil NT. Yamamoto Y. J. Org. Chem. 2004, 69: 5139

Search in Google Scholar
4b Chen C. Dormer PG. J. Org. Chem. 2005, 70: 6964

Search in Google Scholar
4c Zhu W. Ma D. Chem. Commun. 2004, 888
4d Evindar G. Batey R. J. Org. Chem. 2006, 71: 1802

Search in Google Scholar
4e Sreedhar B. Reddy PS. Kumar NS. Tetrahedron Lett. 2006, 47: 3055

Search in Google Scholar
4f Jin T. Kamijo S. Yamamoto Y. Eur. J. Org. Chem. 2004, 3789
5a Tietze LF. Brasch G. Gericke KM. Domino Reactions in Organic Synthesis Wiley-VCH; Weinheim: 2006.
5b Tietze LF. Rackelmann N. Pure Appl. Chem. 2004, 76: 1967

Search in Google Scholar
6 Khoshkholgh MJ. Balalaie S. Gleiter R. Rominger F. Tetrahedron 2008, 64: 10924

Crossref Search in Google Scholar
7a Elguero J. In Comprehensive Heterocyclic Chemistry Vol. 5: Katritzky AP. Pergamon Press; Oxford: 1984. p.277-282

Search in Google Scholar
7b Singh SK. Reddy PG. Rao KS. Lohray BB. Misra P. Rajjak SA. Rao YK. Venkatewarlu A. Bioorg. Med. Chem. Lett. 2004, 14: 499

Search in Google Scholar
7c Chimenti F. Bolasco A. Manna F. Secci D. Chimenti P. Befani O. Turini P. Giovannini V. Mondovi B. Cirilli R. Torre FL. J. Med. Chem. 2004, 47: 2017

Search in Google Scholar
9a Himo F. Lovell T. Hilgraf R. Rostovtsev VV. Noodleman L. Sharpless KB. Fokin VV. J. Am. Chem. Soc. 2005, 127: 210

Search in Google Scholar
9b Yoo EJ. Ahlquist M. Bae I. Sharpless KB. Fokin VV. Chang S. J. Org. Chem. 2008, 73: 5520

Search in Google Scholar
10 Fürstner A. Stimson CC. Angew. Chem. Int. Ed. 2007, 46: 8845

Crossref PubMed Search in Google Scholar

8

General Procedures for the Intramolecular Domino Knoevenagel-Hetero-Diels-Alder Reaction
A solution of compounds 1a-g (1 mmol), 2a,b (1.2 mmol), CuI (0.2 equiv, 38 mg), and Et₃N (1 mmol, 0.06 mL) in MeOH (25 mL) was refluxed for 8 h. The progress of reaction was monitored by TLC. The precipitated solid was filtered, washed with cold EtOH, and recrystallized in CH₂Cl₂.
Selected Spectroscopic Data
3-(3-Chlorophenyl)-1-methyl-3,11b-dihydro-6 H -chromeno[4′,3′:4,5]pyrano[2,3- c ]pyrazole (3a) White solid; mp 167-168 ˚C. IR (KBr): 1686, 1596 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 2.49 (s, 3 H, Me), 4.70 (d, J = 12.0 Hz, 1 H, OCH), 4.71 (s, 1 H, CH), 4.86 (d, J = 12.0 Hz, 1 H, OCH), 6.69 (s, 1 H, =CH), 6.85 (d, J = 8.0 Hz, 1 H, H_Ar), 6.91 (t, J = 7.3 Hz, 1 H, H_Ar), 7.07 (d, J = 7.6 Hz, 1 H, H_Ar), 7.17 (t, J = 7.6 Hz, 1 H, H_Ar), 7.22 (d, J = 7.9 Hz, 1 H, H_Ar), 7.33 (t, J = 8.0 Hz, 1 H, H_Ar), 7.64 (d, J = 8.1, 1 H, H_Ar), 7.78 (s, 1 H, H_Ar) ppm. ^¹³C NMR (125 MHz, CDCl₃): δ = 8.4, 15.2, 62.7, 63.0, 83.9, 117.6, 118.9, 121.1, 121.7, 126.6, 129.3, 130.1, 130.7, 134.9, 153.2 ppm. HRMS (EI, 70 eV): m/z calcd for C₂₀H₁₅N₂O₅ ^³5Cl [M]⁺ : 350.0822; found: 350.0822; m/z calcd for C₂₀H₁₅N₂O₅ ^³7Cl [M + 2]⁺ : 352.0792; found: 352.0783.
10-Bromo-1-methyl-3-phenyl-3,11b-dihydro-6 H -chromeno[4′,3′:4,5]pyrano[2,3- c ]pyrazole (3b)
Light brown solid; mp 195-196 ˚C. IR (KBr): 1683, 1600 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 2.49 (s, 3 H, Me), 4.70 (d, J = 12.0 Hz, 1 H, OCH), 4.71 (s, 1 H, CH), 4.83 (d, J = 12.0 Hz, 1 H, OCH), 6.69 (s, 1 H, =CH), 6.72 (d, J = 8.6 Hz, 1 H, H_Ar), 7.18 (d, J = 2.2 Hz, 1 H, H_Ar), 7.24 (dd, J = 8.6, 2.2 Hz, 1 H, H_Ar), 7.28 (t, J = 7.5 Hz, 1 H, H_Ar), 7.44 (t, J = 7.9 Hz, 1 H, H_Ar), 7.70 (d, J = 7.9 Hz, 2 H, H_Ar) ppm. ^¹³C NMR (125 MHz, CDCl₃): δ = 13.5, 31.1, 67.2, 94.8, 109.7, 112.3, 118.4, 120.5, 125.9, 128.2, 128.5, 129.2, 134.9, 137.3, 145.7, 146.0, 152.3 ppm. HRMS (EI, 70 eV): m/z calcd for C₂₀H₁₅N₂O₅ ⁷⁹Br [M]⁺ : 394.0317; found: 394.0357; m/z calcd for C₂₀H₁₅N₂O₅ ^8¹Br [M + 2]⁺ : 396.0297; found: 396.0314.
10-Bromo-3-(3-chlorophenyl)-1-methyl-3,11b-dihydro-6 H -chromeno[4′,3′:4,5]pyrano[2,3- c ]pyrazole (3c) White solid. IR (KBr): 1474 cm^-¹. ^¹H NMR (500 MHz, DMSO-d ₆): δ = 2.39 (s, 3 H, Me), 4.80 (s, 2 H, OCH₂), 4.88 (s, 1 H, CH), 6.77 (d, J = 8.5 Hz, 1 H, H_Ar), 7.00 (s, 1 H, =CH), 7.14 (s, 1 H, H_Ar), 7.29 (d, J = 8.5 Hz, 1 H, H_Ar), 7.36 (d, J = 7.9 Hz, 1 H, H_Ar), 7.49 (t, J = 7.9 Hz, 1 H, H_Ar), 7.67 (d, J = 7.9 Hz, 1 H, H_Ar), 7.73 (s, 1 H, H_Ar) ppm. ^¹³C NMR (125 MHz, DMSO-d ₆): δ = 13.4, 30.1, 66.4, 95.4, 109.2, 110.9, 118.2, 118.7, 119.4, 125.6, 127.5, 129.3, 130.2, 130.6, 133.1, 135.7, 138.2, 145.5, 146.3, 152.3 ppm. HRMS (EI, 70 eV): m/z calcd for C₂₀H₁₄N₂O₂ ^³5Cl⁷⁹Br [M]⁺ : 427.9937; found: 427.9948; m/z calcd for C₂₀H₁₄N₂O₂ ^³5Cl^8¹Br [M + 2]⁺ : 429.9907; found: 429.9931; m/z calcd for C₂₀H₁₄N₂O₂ ^³7Cl^8¹Br [M + 4]⁺ : 431.9877; found: 431.9912.
10-Nitro-1-methyl-3-phenyl-3,11b-dihydro-6 H -chromeno[4′,3′:4,5]pyrano[2,3- c ]pyrazole (3d) Light brown solid; mp 208-209 ˚C. IR (KBr): 1678, 1601, 1514 cm^-¹; ^¹H NMR (500 MHz, CDCl₃): δ = 2.59 (s, 3 H, Me), 4.80 (s, 1 H, CH), 4.83 (d, J = 12.1 Hz, 1 H, OCH), 4.93 (d, J = 12.1 Hz, 1 H, OCH), 6.78 (s, 1 H, =CH), 6.90 (d, J = 8.9 Hz, 1 H, H_Ar), 7.29 (t, J = 7.7 Hz, 1 H, H_Ar), 7.44 (t, J = 7.7 Hz, 2 H, H_Ar), 7.70 (d, J = 7.7 Hz, 2 H, H_Ar), 8.06 (dd, J = 2.0, 8.9 Hz, 1 H, H_Ar), 8.09 (d, J = 2.0 Hz, 1 H, H_Ar) ppm. ^¹³C NMR (125 MHz, CDCl₃): δ = 14.3, 31.8, 68.5, 108.6, 117.7, 121.1, 122.9, 124.3, 126.6, 127.7, 129.1, 136.5, 137.8, 159.2 ppm. HRMS (EI, 70 eV): m/z calcd for C₂₀H₁₅N₃O₄ [M]⁺ : 361.1063; found: 361.1066.
10-Nitro-3-(3-chlorophenyl)-1-methyl-3,11b-dihydro-6 H -chromeno[4′,3′:4,5]pyrano[2,3- c ]pyrazole (3e) Light brown solid; mp 215-216 ˚C. IR (KBr): 1686, 1599, 1580, 1510 cm^-¹. ^¹H NMR (500 MHz, DMSO-d ₆): δ = 2.48 (s, 3 H, Me), 4.97 (s, 2 H, OCH and CH), 5.01 (s, 1 H, OCH), 7.00 (d, J = 9.0 Hz, 1 H, H_Ar), 7.24 (s, 1 H, =CH), 7.37 (dd, J = 6.5, 1.0 Hz, 1 H, H_Ar), 7.51 (t, J = 8.0 Hz, 1 H, H_Ar), 7.67 (dd, J = 8.0, 1.0 Hz, 1 H, H_Ar), 7.74 (t, J = 2.0 Hz, 1 H, H_Ar), 7.87 (d, J = 1.8 Hz, 1 H, H_Ar), 8.05 (dd, J = 9.0, 2.8 Hz, 1 H, H_Ar) ppm. ^¹³C NMR (125 MHz, DMSO-d ₆): δ = 13.9, 30.6, 66.3, 67.6, 95.5, 108.3, 117.8, 118.7, 119.9, 121.9, 124.1, 126.2, 127.7, 131.0, 133.6, 136.9, 138.5, 140.3, 145.9, 146.6, 159.2 ppm. HRMS (EI, 70 eV): m/z calcd for C₂₀H₁₄N₃O₄ ^³5Cl [M]⁺ : 395.0673; found: 395.0663; m/z calcd for C₂₀H₁₄N₃O₄ ^³7Cl [M + 2]⁺ : 397.0643; found: 397.0622.
3-(3-Chlorophenyl)-1,10-dimethyl-3,11b-dihydro-6 H -chromeno[4′,3′:4,5]pyrano[2,3- c ]pyrazole (3f) White solid; mp 194-195 ˚C. IR (KBr): 1683, 1597, 1512 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 2.26 (s, 3 H, Me), 2.50 (s, 3 H, Me), 4.68 (d, J = 11.9 Hz, 1 H, OCH), 4.69 (s, 1 H, CH), 4.83 (d, J = 11.9 Hz, 1 H, OCH), 6.67 (s, 1 H, =CH), 6.76 (d, J = 8.2 Hz, 1 H, H_Ar), 6.86 (s, 1 H, H_Ar), 6.97 (dd, J = 8.2, 1.7 Hz, 1 H, H_Ar), 7.23 (m, 1 H, H_Ar), 7.35 (t, J = 8.0 Hz, 1 H, H_Ar), 7.65 (dd, J = 8.0, 1.7 Hz, 1 H, H_Ar), 7.79 (t, J = 2.0 Hz, 1 H, H_Ar) ppm. ^¹³C NMR (125 MHz, CDCl₃): δ = 14.2, 20.7, 31.5, 67.3, 96.4, 111.7, 117.0, 118.4, 120.6, 126.0, 126.1, 127.5, 128.7, 130.1, 130.2, 134.7, 134.8, 139.1, 146.5, 1147.4, 151.4 ppm. HRMS (EI, 70 eV): m/z calcd for C21H17N2O235Cl [M]+: 364.0970; found 364.0959; m/z calcd for C21H17N2O237Cl [M + 2]+: 366.0949; found 366.0964.

8-Bromo-10-chloro-3-(3-chlorophenyl)-1-methyl-3,11b-dihydro-6 H -chromeno[4′,3′:4,5]pyrano[2,3- c ]pyrazole (3g) Light brown solid; mp 208.5-209.5 ˚C. IR (KBr): 1682, 1596 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): d = 2.46 (s, 3 H, Me), 4.69 (s, 1 H, CH), 4.85 (d, J = 12.0 Hz, 1 H, OCH), 4.95 (d, J = 12.0 Hz, 1 H, OCH), 6.74 (s, 1 H, =CH), 6.96 (s, 1 H, H_Ar), 7.23-7.42 (m, 3 H, H_Ar), 7.64 (d, J = 2.0 Hz, 1 H, H_Ar), 7.78 (d, J = 2.0 Hz, 1 H, H_Ar) ppm. ^¹³C NMR (125 MHz, CDCl₃): d = 14.0, 31.7, 68.5, 95.2, 109.7, 111.5, 118.5, 120.7, 125.0, 125.8, 126.3, 130.1, 130.2, 131.2, 134.8, 135.6, 138.9, 146.3, 146.9, 149.1 ppm. HRMS (EI, 70 eV): m/z calcd for C₂₀H₁₄N₂O₂ ^³5Cl₂ ⁷⁹Br [M]⁺ : 461.9538; found: 461.9547; m/z calcd for C₂₀H₁₄N₂O₂ ^³5Cl₂ ^8¹Br [M + 2]⁺ : 463.9517; found: 463.9500; m/z calcd for C₂₀H₁₄N₂O₂ ^³5Cl^³7Cl^8¹Br [M + 4]⁺ : 465.9487; found: 465.9485.
8-Bromo-10-chloro-1-methyl-3-phenyl-3,11b-dihydro-6 H -chromeno[4′,3′:4,5]pyrano[2,3- c ]pyrazole (3h) White solid; mp 197.5-199 ˚C. IR (KBr): 1683, 1597, 1518 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): d = 2.47 (s, 3 H, Me), 4.68 (s, 1 H, CH), 4.84 (d, J = 12.0 Hz, 1 H, OCH), 4.95 (d, J = 12.0 Hz, 1 H, OCH), 6.70 (s, 1 H, =CH), 6.99 (d, J = 2.1 Hz, 1 H, H_Ar), 7.28 (t, J = 7.7 Hz, 1 H, H_Ar),7.41 (d, J = 2.1 Hz, 1 H, H_Ar), 7.43 (t, J = 7.7 Hz, 2 H, H_Ar), 7.70 (d, J = 7.7 Hz, 2 H, H_Ar) ppm. ^¹³C NMR (125 MHz, CDCl₃): d = 14.1, 31.8, 68.6, 94.9, 109.4, 111.5, 120.9, 125.1, 125.8, 126.5, 129.1, 130.3, 131.1, 135.8, 137.8, 146.1, 146.3, 149.1 ppm. HRMS (EI, 70 eV): m/z calcd for C₂₀H₁₄N₂O₂ ^³5Cl⁷⁹Br [M]⁺ : 427.9928; found: 427.9980; m/z calcd for C₂₀H₁₄N₂O₂ ^³5Cl^8¹Br [M + 2]⁺ : 429.9907; found: 429.9946.
8,10-Dichloro-1-methyl-3-phenyl-3,11b-dihydro-6 H -chromeno[4′,3′:4,5]pyrano[2,3- c ]pyrazole (3i) White solid; mp 208-209 ˚C. IR (KBr): 1676, 1598, 1519 cm^-¹. ^¹H NMR (500 MHz, DMSO-d ₆): d = 2.39 (s, 3 H, Me), 4.91 (s, 1 H, CH), 4.92 (d, J = 12.0 Hz, 1 H, OCH), 4.96 (d, J = 12.0 Hz, 1 H, OCH), 6.85 (d, J = 2.0 Hz, 1 H, H_Ar), 7.16 (s, 1 H, =CH), 7.31 (t, J = 7.5 Hz, 1 H, H_Ar),7.44 (d, J = 2.0 Hz, 1 H, H_Ar), 7.48 (t, J = 7.5 Hz, 2 H, H_Ar), 7.67 (d, J = 7.5 Hz, 2 H, H_Ar) ppm. ^¹³C NMR (125 MHz, CDCl₃): d = 13.7, 30.8, 67.8, 94.9, 108.6, 120.4, 121.6, 123.7, 124.0, 126.4, 127.6, 129.2, 130.7, 136.6, 137.3, 145.6, 145.8, 148.0 ppm. HRMS (EI, 70 eV): m/z calcd for C₂₀H₁₄N₂O₂ ^³5Cl₂ [M]⁺ : 384.0432; found: 384.0398; m/z calcd for C₂₀H₁₄N₂O₂ ^³5Cl^³7Cl [M + 2]⁺ : found: 386.0365; 386.0384; m/z calcd for C₂₀H₁₄N₂O₂ ^³7Cl₂ [M + 4]⁺ : 388.0373; found: 388.0368.
8-Methoxy-1-methyl-3-phenyl-3,11b-dihydro-6 H -chromeno[4′,3′:4,5]pyrano[2,3- c ]pyrazole (3j)
Light brown solid; mp 214-215 ˚C. IR (KBr): 1686, 1597 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): d = 2.49 (s, 3 H, Me), 3.88 (s, 3 H, OMe), 4.75 (s, 1 H, CH), 4.83 (d, J = 12.0 Hz, 1 H, OCH₂), 4.91 (d, J = 12.0 Hz, 1 H, OCH₂), 6.68 (s, 1 H, =CH), 6.74 (d, J = 7.7 Hz, 1 H, H_Ar), 6.80 (d, J = 7.7 Hz,
1 H, H_Ar), 6.87 (t, J = 7.9 Hz, 1 H, H_Ar), 7.26 (t, J = 7.3 Hz, 1 H, H_Ar), 7.42 (t, J = 7.8 Hz, 2 H, H_Ar), 7.70 (d, J = 7.9, 2 H, H_Ar) ppm. ^¹³C NMR (125 MHz, CDCl₃): d = 12.0, 56.1, 63.4, 83.7, 115.1, 119.5, 121.1, 121.3, 121.5, 123.1, 126.6, 126.8, 127.7, 128.9, 129, 135.8, 141, 145.7, 147.4, 148.4 ppm. HRMS (EI, 70 eV): m/z calcd for C₂₁H₁₈N₂O₃ [M]⁺ : 346.1318; found: 346.1331.