Generic placeholder image

Current Organic Synthesis


ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Research Article

Cationic Ruthenium-Catalyzed Bis-Homo-Diels-Alder Cycloaddition

Author(s): Dina Petko, Matthew Stratton, Samuel Koh and William Tam*

Volume 16, Issue 5, 2019

Page: [787 - 792] Pages: 6

DOI: 10.2174/1570179416666190401204448

Price: $65


Objective: The ruthenium-catalyzed Bis-Homo-Diels-Alder cycloaddition between 1,5- cyclooctadiene and alkynes was explored, and the use of commercially available cationic catalysts was investigated. It was noted that [CpRu(CH3CN)3]PF6 was effective at catalyzing this cycloaddition and yields of the desired tricyclo[,5]dec-7-ene adduct ranging from 13 to 83% were achieved using this cationic catalyst. Several cycloadducts that were previously unobtainable with the use of the neutral (Cp*RuCl(COD) catalysts were also successfully made using [CpRu(CH3CN)3]PF6 albeit in low yields.

Methods: Commercially available, and previously synthesized alkynes were combined with 1,5-cyclooctadiene and treated with a ruthenium catalyst within a glovebox. The reaction mixture was stirred for 72h at temperatures ranging from 25 to 70oC. The desired cycloadduct was then isolated using flash column chromatography and analyzed and characterized using NMR, IR and MS.

Results: Several previously unattainable adducts were synthesized using the cationic [CpRu(CH3CN)3]PF6. When this catalyst was compared to the neutral Cp*RuCl(COD) greater yields were observed.

Conclusion: The present study describes an improved method for the formation of the tricyclo[,5]dec-7- ene framework using a commercially available cationic ruthenium catalyst. It was noted that the use of [CpRu(CH3CN)3]PF6 led to improved yields when compared to Cp*RuCl(COD).

Keywords: Alkynes, Bis-Homo-Diels-Alder, cationic, cycloaddition, ruthenium, 1, 5-cyclooctadiene.

Graphical Abstract
Trost, B.M.; Fleming, I.; Paquette, L.A. Comprehensive Organic Synthesis, Vol. 5, Chapters 1-9; Pergamon: Oxford. 1991.
Curran, D.P. Advances in Cycloaddition, Vols. 1-3, JAI Press: Greenwich. 1991.
Lautens, M.; Klute, W.; Tam, W. Transition metal-mediated cycloaddition reactions. Chem. Rev., 1996, 96, 49-92.
Hegedus, L.S. Transition metals in organic synthesis. Highlights for the year 1995. Coord. Chem. Rev., 1997, 161, 129-255.
Wender, P.A.; Love, J.A. Advances in Cycloaddition; JAI Press: Greenwich, 1999, Vol. 5, pp. 1-45.
Wender, P.A.; Ihle, N.C. Nickel-catalyzed intramolecular [4+4]-cycloadditions: A new method for the synthesis of polycycles containing eight-membered rings. J. Am. Chem. Soc., 1986, 108, 4678-4679.
Wender, P.A.; Jenkins, T.E. Nickel-catalyzed intramolecular [4+2] dienyne cycloadditions: an efficient new method for the synthesis of polycycles containing cyclohexa-1,4-dienes. J. Am. Chem. Soc., 1989, 111, 6432-6434.
Wender, P.A.; Smith, T.E. Transition metal-catalyzed intramolecular [4+2] cycloadditions: Initial studies on stereochemistry and on steroid and vitamin D analog syntheses. J. Org. Chem., 1995, 60, 2962-2963.
Wender, P.A.; Smith, T.E. Transition metal-catalyzed intramolecular [4+2] cycloadditions: A novel method for the assembly of nitrogen heterocycles and its application to yohimban alkaloid synthesis. J. Org. Chem., 1996, 61, 824-825.
Wender, P.A.; Smith, T.E. Transition metal-catalyzed intramolecular [4+2] cycloadditions: Mechanistic and synthetic investigations. Tetrahedron, 1998, 54, 1255-1275.
Jolly, R.S.; Luedtke, G.; Sheehan, D.; Livinghouse, T. Novel cyclization reactions on transition metal templates. The catalysis of intramolecular [4+2] cycloadditions by low-valent rhodium complexes. J. Am. Chem. Soc., 1990, 112, 4965-4966.
Wender, P. Jenkins, T.E.; Suzuki, S. Transition metal-catalyzed intramolecular [4+2] diene-allene cycloadditions: A convenient synthesis of angularly substituted ring systems with provision for catalyst-controlled chemo- and stereocomplementarity. J. Am. Chem. Soc., 1995, 117, 1843-1844.
O’Mahony, D.J.R.; Belanger, D.B.; Livinghouse, T. On the counterion dependence of the rhodium(i)-catalysed [4+2] cycloaddition – a remarkable accelerating effect of the hexafluoroantimonate anion. Synlett, 1998, 443-445.
Gilbertson, S.R.; Hoge, G.S. Rhodium catalyzed intramolecular [4+2] cycloisomerization reactions. Tetrahedron Lett., 1998, 39, 2075-2078.
Gilbertson, S.R.; Hoge, G.S.; Genov, D.G. Rhodium-catalyzed asymmetric [4+2] cycloisomerization reactions. J. Org. Chem., 1998, 63, 10077-10080.
Murakami, M.; Ubukata, M.; Itami, K.; Ito, Y. Rhodium-catalyzed intermolecular [4+2] cycloaddition of unactivated substrates. Angew. Chem. Int. Ed., 1998, 37, 2248-2250.
Paik, S.; Son, S.U.; Chung, Y.K. Highly efficient intra- and intermolecular [4+2] cycloaddition reaction catalyzed by rhodium complex. Org. Lett., 1999, 1, 2045-2047.
Wang, B.; Cao, P.; Zhang, X. An efficient Rh-catalyst system for the intramolecular [4+2] and [5+2] cycloaddition reactions. Tetrahedron Lett., 2000, 41, 8041-8844.
Heath, H.; Wolfe, B.; Livinghouse, T.; Bae, S.K. New methods for the synthesis of P-chirogenic diphosphines: An application to the development of an improved asymmetric variation of the Rh(I)-catalyzed [4+2] cycloaddition. Synthesis, 2001, 2341-2347.
O’Mahony, D.J.R.; Belanger, D.B.; Livinghouse, T. Substrate control of stereoselection in rhodium(I) catalyzed intramolecular [4+2] cycloaddition reaction. Org. Biomol. Chem., 2003, 1, 2038.
Witulski, B.; Lumtscher, J.; Bergsträber, U. First thermal and transition metal catalysed intramolecular [4+2] cycloaddition reactions with N-tethered ynamides. Synlett, 2003, 2003, 708-710.
Motoda, D.; Kinoshita, H.; Shinokubo, H.; Oshima, K. Phosphane-free rhodium catalyst in an anionic micellar system for [4+2] annulation of dienynes. Angew. Chem. Int. Ed., 2004, 43, 1860-1862.
Hilt, G.; Korn, T.J. An efficient cobalt catalyst for the neutral Diels–Alder reaction of acyclic 1,3-dienes with internal alkynes. Tetrahedron Lett., 2001, 42, 2783-2785.
Hilt, G.; Korn, T.J. An efficient cobalt catalyst for the neutral Diels-Alder reaction of acyclic 1,3-dienes with internal alkynes. Tetrahedron Lett., 2001, 42, 2783-2785.
Hilt, G.; Smolko, K.I.; Lotsch, B.V. Cobalt(I)-catalyzed neutral Diels-Alder reactions of oxygen-functionalized acyclic 1,3-dienes with alkynes. Synlett,2002, 2002, 1081-1085. (d) Hilt, G.; Lüers, S. Cobalt(I)-catalyzed 1,4-hydrovinylation reactions of 1,3-dienes with functionalized terminal alkenes under mild conditions. Synthesis, 2002, 2002, 609-618.
Hilt, G.; Smolko, K.I. Cobalt(I)-catalyzed neutral Diels-Alder reactions of 1,3-diynes with acyclic 1,3-dienes. Synthesis,2002, 2002, 686-692. (f) Hilt, G.; Smolko, K.I. Alkynylboronic esters as efficient dienophiles in cobalt-catalyzed Diels-Alder reactions. Angew. Chem. Int. Ed., 2003, 42, 2795-2797.
Hilt, G.; Lüers, S. Alkynyl sulfides as dienophilesin cobalt-catalyzed Diels-Alder reactions. Synthesis, 2003, 2003, 1784-1786.
Hilt, G.; Lüers, S.; Harms, K. The first broad application of alkynyl sulfides as dienophiles in cobalt(I)-catalyzed Diels-Alder reactions. J. Org. Chem., 2004, 69, 624-630.
Hilt, G.; Lüers, S.; Smolko, K.I. A two-step reaction sequence for the syntheses of tetrahydronaphthalenes. Org. Lett., 2005, 7, 251-253.
Shibata, T.; Takasaku, K.; Takesue, Y.; Hirata, N.; Takagi, K. Iridium complex-catalyzed enantioselective intramolecular [4+2] cycloaddition of dieneynes. Synlett, 2002, 2002, 1681-1682.
Murakami, M.; Itami, K.; Ito, Y. Directed intermolecular [4+2] cycloaddition of unactivated 1,3-diene substrates with high regio- and stereoselectivities. J. Am. Chem. Soc., 1997, 119, 7163-7164.
Murakami, M.; Minamida, R.; Itami, K.; Sawamura, M.; Ito, Y. Palladium-catalysed asymmetric [4+2] cycloaddition of vinylallene with 1,3-diene. Chem. Commun., 2000, 2000, 2293-2294.
Lautens, M.; Tam, W. Transition-metal-catalyzed cycloaddition reactions of bicyclo[2.2.1]hepta-2,5-dienes (norbornadienes). In: Advances in Metal- Organic Chemistry, Liebeskind, L.S, Ed., JAI Press: Greenwich CT, , 1998. Vol. 6, pp. 49-101
Lyons, J.E.; Myers, H.K.; Schneider, A. Selective homo-Diels-Alder addition of acetylenic hydrocarbons to norbornadiene catalyzed by a cobalt complex. Chem. Commun., 1978, 1978, 636-638.
Lautens, M.; Crudden, C.M. Scope of the cobalt-catalyzed [2+2+2] homo-Diels-Alder reaction. Organometallics, 1989, 8, 2733-2735.
Lautens, M.; Lautens, J.C.; Smith, A.C. Catalytic asymmetric induction in the homo Diels-Alder reaction. J. Am. Chem. Soc., 1990, 112, 5627-5628.
Lautens, M.; Tam, W.; Edwards, L.G. Cobalt-catalyzed intramolecular homo Diels-Alder reactions. J. Org. Chem., 1992, 57, 8-9.
Lautens, M.; Tam, W.; Sood, C. Enantioselective cobalt-catalyzed [4.pi.+2.pi.+2.pi.] cycloadditions. J. Org. Chem., 1993, 58, 4513-4515.
Lautens, M.; Tam, W.; Lautens, J.C.; Edwards, L.G.; Crudden, C.M.; Smith, A.C. Cobalt-catalyzed [2.pi.+2.pi.+2.pi.] (Homo-Diels-Alder) and [2.pi.+2.pi.+4.pi.] cycloadditions of bicyclo[2.2.1]hepta-2,5-dienes. J. Am. Chem. Soc., 1995, 117, 6863.
Duan, I-F.; Cheng, C-H.; Shaw, J-S.; Cheng, S-S.; Liou, K-F. Homo-Diels-Alder cycloadditions catalyzed by cobalt-triphenylphosphine-zinc systems. Chem. Commun., 1991, 1991, 1347-1348.
Binger, P.; Albus, S. Deltacyclene formation catalysed by cationic Co(II) complexes. J. Organomet. Chem., 1995, 493, C6-C8.
Chen, Y.; Snyder, J.K. Metal-catalyzed [4+2+2] Cycloadditions: cycloadducts of substituted norbornadienes and their opening with Zeise’s dimer. J. Org. Chem., 1998, 63, 2060-2061.
Hilt, G.; du Mesnil, F-X. An improved cobalt catalyst for homo Diels-Alder reactions of acyclic 1,3-dienes with alkynes. Tetrahedron Lett., 2000, 41, 6757-6761.
Pardigon, O.; Tenaglia, A.; Buono, G. Enantioselective syntheses of monofunctionalized deltacyclenes using a [CoI2/Zn] catalytic system. J. Org. Chem., 1995, 60, 1868-1871.
Tenaglia, A.; Giordano, L. Ruthenium(II)-catalyzed homo-Diels-Alder reactions of disubstituted alkynes and norbornadiene. Tetrahedron Lett., 2004, 45, 171.
Tenaglia, A.; Gaillard, S. Ruthenium-catalyzed intramolecular Homo-Diels-Alder reaction of alkyne-tethered norbornadienes. An entry to fused angular triquinanes. Org. Lett., 2007, 9, 3607-3610.
Kettles, T.J.; Cockburn, N.; Tam, W. Ruthenium-catalyzed Homo Diels-Alder [2+2+2] cycloadditions of alkynyl phosphonates with bicyclo[2.2.1]hepta-2,5-diene. J. Org. Chem., 2011, 76, 6951-6957.
Trost, B.M.; Imi, K.; Indolese, A.F. 1,5-cyclooctadiene as a bis-homodiene partner in a metal-catalyzed [4+2] cycloaddition. J. Am. Chem. Soc., 1993, 115, 8831-8832.
Alvarez, P.; Gimeno, J.; Lastra, E.; García-Granda, S.; Van der Maelen, J.F.; Bassetti, M. Synthesis and reactivity of indenyl ruthenium(II) complexes containing the labile ligand 1,5-cyclooctadiene (COD): Catalytic activity of [Ru(η5-C9H7)Cl(COD)]. Organometallics, 2001, 20, 3762-3771.
Huang, X.; Lin, Z. Density functional theory studies of ruthenium-catalyzed Bis-Diels-Alder cycloaddition of 1,5-cyclooctadiene with alkynes. Organometallics, 2003, 22, 5478-5484.
Petko, D.; Stratton, M.; Tam, W. Ruthenium-catalyzed Bis-Homo-Diels-Alder reaction: searching for commercially available catalysts and expanding the scope of reaction. Can. J. Chem., 2018, 96, 1115-1121.
Hasinoff, B.B.; Creighton, A.M.; Kozlowska, H.; Thampatty, P.; Allan, W.P.; Yalowich, J.C. Mitindomide is a catalytic inhibitor of DNA topoisomerase II that acts at the bisdioxopiperazine binding site. Mol. Pharmacol., 1997, 52, 839-845.
Leverrier, A.; Awang, K.; Guéritte, F.; Litaudon, M. Pentacyclic polyketides from Endiandra kingiana as inhibitors of the Bcl-xL/Bak interaction. Phytochemistry, 2011, 72, 1443-1452.
Naota, T.; Takaya, H.; Murahashi, S-I. Ruthenium-catalyzed reactions for organic synthesis. Chem. Rev., 1998, 98, 2599-2660.
Grubbs, R.H.; Chang, S. Recent advances in olefin metathesis and its application in organic synthesis. Tetrahedron, 1998, 54, 4413-4450.
Fürstner, A. Topics in Organometallic Chemistry; Fürstner, A., Ed.; Springer: Berlin, Heidelberg, 1998, Vol. 1, pp. 37-72.
Trost, B.M.; Toste, F.D.; Pinkerton, A.B. Non-metathesis ruthenium-catalyzed C-C bond formation. Chem. Rev., 2001, 101, 2067-2096.
Bruneau, C.; Dixneuf, P.H. Topics in Organometallic Chemistry, Vol. 11, Springer-Verlag GmbH: Berlin, New York, 2004
Murahashi, S.-I. Ruthenium in Organic Synthesis, Wiley-VCH: Weinhein. 2004.
Machin, B.P.; Howell, J.; Mandel, J.; Blanchard, N.; Tam, W. Ruthenium-catalyzed nucleophilic ring-opening reactions of a 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols. Org. Lett., 2009, 11, 2077-2080.
Rüba, E.; Schmid, R.; Kirchner, K.; Calhorda, M.J. Ruthenium-mediated cyclotrimerization of alkynes utilizing the cationic complex [RuCp(CH3CN)3]PF6. J. Organomet. Chem., 2003, 682, 204-211.

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy