Pauson–Khand reaction

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Pauson–Khand reaction
Named after Peter Ludwig Pauson
Ihsan Ullah Khand
Reaction type Ring forming reaction
Identifiers
Organic Chemistry Portal pauson-khand-reaction
RSC ontology ID RXNO:0000464

The Pauson–Khand reaction (or PKR or PK-type reaction) is a chemical reaction described as a [2+2+1] cycloaddition between an alkyne, an alkene and carbon monoxide to form a α,β-cyclopentenone.[1][2] The reaction was discovered by Ihsan Ullah Khand (1935-1980), who was working as a postdoctoral associate with Peter Ludwig Pauson (1925-2013)[3] at the University of Strathclyde in Glasgow. This reaction was originally mediated by stoichiometric amounts of dicobalt octacarbonyl, but newer versions are both more efficient and catalytic.[4][5] An example of a newer version is the use of [RhCl(CO)2)]2 in the synthesis of (+)-Phorbol by Baran et al. In addition to using a rhodium catalyst this synthesis features an intramolecular cyclization that results in the normal 5-membered α,β-cyclopentenone as well as 7-membered ring.[6]

PK reaction

With unsymmetrical alkenes or alkynes, regioselectivity can be problematic, but less so with intramolecular reactions.[7]

PK reaction example

The reaction works with both terminal and internal alkynes although internal alkynes tend to give lower yields. The order of reactivity for the alkene is strained cyclic alkene > terminal alkene > disubstituted alkene > trisubstituted alkene. Unsuitable alkenes are tetrasubstituted alkenes and alkenes with strongly electron withdrawing groups.[8]

Variations[edit]

Wilkinson's catalyst, based on the transition metal rhodium, also effectively catalyses PK reactions but requires silver triflate as a co-catalyst.[9]

PK reaction with Wilkinson's catalyst

Molybdenum hexacarbonyl is a carbon monoxide donor in PK-type reactions between allenes and alkynes with dimethyl sulfoxide in toluene.[10]

PK reaction with molybdenum hexacarbonyl

Cyclobutadiene also lends itself to a [2+2+1] cycloaddition although this reactant is generated in situ from decomplexation of stable cyclobutadiene iron tricarbonyl with ceric ammonium nitrate (CAN).[11]

Pauson Khand reaction Seigal 2005

See also[edit]

References[edit]

  1. ^ P. L. Pauson and I. U. Khand. Ann. N. Y. Acad. Sci. 1977, 295, 2.
  2. ^ Blanco-Urgoiti, J.; Añorbe, L.; Pérez-Serrano, L.; Domínguez, G.; Pérez-Castells, J. Chem. Soc. Rev. 2004, 33, 32. doi:10.1039/b300976a
  3. ^ H. Werner. Angew. Chem. Int. Ed. 2014, 53, 3309. doi:10.1002/anie.201400432
  4. ^ Schore, N. E. "The Pauson–Khand Cycloaddition Reaction for Synthesis of Cyclopentenones" Org. React., 1991, 40, 1. doi:10.1002/0471264180.or040.01
  5. ^ S. E. Gibson and A. Stevenazzi "The Pauson–Khand Reaction: the Catalytic Age Is Here!" Angew. Chem. Int. Ed., 2003, 42, 1800-1810. doi:10.1002/anie.200200547
  6. ^ Kawamura, Shuhei; Chu, Hang; Felding, Jakob; Baran, Phil S. (2016-03-23). "Nineteen-step total synthesis of (+)-phorbol". Nature. 532 (7597): 90–93. Bibcode:2016Natur.532...90K. doi:10.1038/nature17153. ISSN 1476-4687. PMC 4833603Freely accessible. 
  7. ^ Jeong, Nakcheol; Hwang, Sung Hee; Lee, Youngshin; Chung, Young Keun (1994). "Catalytic version of the Intramolecular Pauson-Khand Reaction". Journal of the American Chemical Society. 116 (7): 3159. doi:10.1021/ja00086a070. 
  8. ^ Strategic applications of named reactions in organic synthesis: background and details mechanisms 2007 László Kürti,Barbara Czakó
  9. ^ Nakcheol Jeong, Byung Ki Sung, Jin Sung Kim, Soon Bong Park,Sung Deok Seo, Jin Young Shin, Kyu Yeol In, Yoon Kyung Choi Pauson–Khand-type reaction mediated by Rh(I) catalysts Pure Appl. Chem., Vol. 74, No. 1, pp. 85–91, 2002. (Online article)
  10. ^ Kent, J (1995). "A new allenic Pauson-Khand cycloaddition for the preparation of α-methylene cyclopentenones". Tetrahedron Letters. 36 (14): 2407. doi:10.1016/0040-4039(95)00315-4. 
  11. ^ Intramolecular [2+2+1] Cycloadditions with (Cyclobutadiene)tricarbonyliron Benjamin A. Seigal, Mi Hyun An, Marc L. Snapper Angewandte Chemie International Edition Volume 44, Issue 31 , Pages 4929 - 4932 2005. doi:10.1002/anie.200501100