:Pauson–Khand reaction

While the mechanism has not yet been fully elucidated, Magnus' 1985 explanation{{Cite journal |last1=Magnus |first1=Philip |last2=Principe |first2=Lawrence M. |date=January 1985 |title=Origins of 1,2- and 1,3-stereoselectivity in dicobaltoctacarbonyl alkene-alkyne cyclizations for the synthesis of substituted bicyclo[3.3.0]octenones. |url=http://dx.doi.org/10.1016/s0040-4039(00)94968-2 |journal=Tetrahedron Letters |volume=26 |issue=40 |pages=4851–4854 |doi=10.1016/s0040-4039(00)94968-2 |issn=0040-4039|url-access=subscription }}, later expanded to {{Cite journal |last1=Magnus |first1=Philip |last2=Exon |first2=Christopher |last3=Albaugh-Robertson |first3=Pamela |date=1985-01-01 |title=Dicobaltoctacarbonyl-alkyne complexes as intermediates in the synthesis of bicyclo[3.3.0]octenones for the synthesis of coriolin and hirsutic acid |url=https://www.sciencedirect.com/science/article/abs/pii/S0040402001914255 |journal=Tetrahedron |language=en |volume=41 |issue=24 |pages=5861–5869 |doi=10.1016/S0040-4020(01)91425-5 |issn=0040-4020|url-access=subscription }} is widely accepted for both mono- and dinuclear catalysts, and was corroborated by computational studies published by Nakamura and Yamanaka in 2001.{{Cite journal |last1=Yamanaka |first1=Masahiro |last2=Nakamura |first2=Eiichi |date=2001-02-01 |title=Density Functional Studies on the Pauson−Khand Reaction |url=https://doi.org/10.1021/ja005565+ |journal=Journal of the American Chemical Society |volume=123 |issue=8 |pages=1703–1708 |doi=10.1021/ja005565+ |issn=0002-7863 |pmid=11456770|url-access=subscription }} The reaction starts with dicobalt hexacarbonyl acetylene complex. Binding of an alkene gives a metallacyclopentene complex. CO then migratorily inserts into an M-C bond. Reductive elimination delivers the cyclopentenone. Typically, the dissociation of carbon monoxide from the organometallic complex is rate limiting.{{sfn|Hartwig|2010}}

[[File:Mech_PKR.png|center|thumb|473x473px|

1:

Alkyne coordination, insertion and ligand dissociation to form an 18-electron complex;

2:

Ligand dissociation to form a 16-electron complex;

3:

Alkene coordination to form an 18-electron complex;

4:

Alkene insertion and ligand association (synperiplanar, still 18 electrons);

5:

CO migratory insertion;

6, 7:

Reductive elimination of metal (loss of [Co₂(CO)₆]);

8:

CO association, to regenerate the active organometallic complex.{{Cite book|author1=Kürti László|author2=Czakó Barbara|title=Strategic Applications of Named Reactions in Organic Synthesis: background and detailed mechanisms|date=2005|publisher=Elsevier Academic Press|isbn=978-0-12-429785-2|location=Amsterdam|oclc=60792519}}

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) > (terminal) > (disubstituted) > (trisubstituted).

With unsymmetrical alkenes or alkynes, the reaction is rarely regioselective, although some patterns can be observed.

File:Intermol_pkr.png and 1-octene produce at least 4 isomeric products. ("tol" = toluene)]]

For mono-substituted alkenes, alkyne substituents typically direct: larger groups prefer the C² position, and electron-withdrawing groups prefer the C³ position.

File:EWG_PKR.png)]]

But the alkene itself struggles to discriminate between the C⁴ and C⁵ position, unless the C² position is sterically congested or the alkene has a chelating heteroatom.

The reaction's poor selectivity is ameliorated in intramolecular reactions. For this reason, the intramolecular Pauson-Khand is common in total synthesis, particularly the formation of 5,5- and 6,5-membered fused bicycles.

File:General_pkr.png

Generally, the reaction is highly syn-selective about the bridgehead hydrogen and substituents on the cyclopentane.

File:Stereosel._pkr.png

Appropriate chiral ligands or auxiliaries can make the reaction enantioselective (see {{Slink||Amine N-oxides}}). BINAP is commonly employed.

File:Cat_pkr.png

Typical Pauson-Khand conditions are elevated temperatures and pressures in aromatic hydrocarbon (benzene, toluene) or ethereal (tetrahydrofuran, 1,2-dichloroethane) solvents. These harsh conditions may be attenuated with the addition of various additives.

File:Comparison_drystate-thermal.png

Adsorbing the metallic complex onto silica or alumina can enhance the rate of decarbonylative ligand exchange as exhibited in the image below.{{Cite journal |last1=Billington |first1=David C. |last2=Willison |first2=Debra |date=1984 |title=A simple organocobalt mediated synthesis of substituted 3-oxabicyclo[3.3.0]oct-6-en-7-ones |url=http://dx.doi.org/10.1016/0040-4039(84)80061-1 |journal=Tetrahedron Letters |volume=25 |issue=36 |pages=4041–4044 |doi=10.1016/0040-4039(84)80061-1 |issn=0040-4039|url-access=subscription }}{{Cite journal |last1=Morimoto |first1=Takashi |last2=Hirano |first2=Masao |last3=Echigoya |first3=Kohki |last4=Sato |first4=Takafumi |date=1986 |title=Oxidation by cobalt(III) acetate. Part 10. Effects of ring substituents on the product distributions in the oxidation of β-methylstyrenes by cobalt(III) acetate in acetic acid |url=http://dx.doi.org/10.1039/p29860001205 |journal=J. Chem. Soc., Perkin Trans. 2 |issue=8 |pages=1205–1209 |doi=10.1039/p29860001205 |issn=0300-9580|url-access=subscription }} This is because the donor posits itself on a solid surface (i.e. silica).{{Clarify|reason=Which molecule is the donor (and what does it donate)? What does it mean to "posit itself" in this context (*position* itself, maybe)?|date=July 2023}} Additionally using a solid support restricts conformational movement (rotamer effect).{{Cite journal |last1=Brown |first1=Scott W. |last2=Pauson |first2=Peter L. |date=1990 |title=The synthesis of nitrogen heterocycles via the intramolecular Khand reaction: formation of tetra- and hexa-hydrocyclopenta[c]pyrrol-5(1H)-ones and hexahydro-6H-2-pyrindin-6-ones |url=http://xlink.rsc.org/?DOI=p19900001205 |journal=Journal of the Chemical Society, Perkin Transactions 1 |language=en |issue=4 |pages=1205–1209 |doi=10.1039/p19900001205 |issn=0300-922X|url-access=subscription }}{{Cite journal |last1=Shilov |first1=Aleksandr E |last2=Shul'pin |first2=Georgiy B |date=1987-05-31 |title=Activation and Catalytic Reactions of Alkanes in Solutions of Metal Complexes |url=https://doi.org/10.1070/RC1987v056n05ABEH003282 |journal=Russian Chemical Reviews |volume=56 |issue=5 |pages=442–464 |bibcode=1987RuCRv..56..442S |doi=10.1070/rc1987v056n05abeh003282 |issn=0036-021X |s2cid=250841849|url-access=subscription }}{{Cite journal |last1=Smit |first1=W.A |last2=Kireev |first2=S.L |last3=Nefedov |first3=O.M |last4=Tarasov |first4=V.A |date=1989-01-01 |title=Methylenecyclopropane as an alkene component in the Khand-Pauson reaction |url=https://www.sciencedirect.com/science/article/abs/pii/S0040403900993134 |journal=Tetrahedron Letters |language=en |volume=30 |issue=30 |pages=4021–4024 |doi=10.1016/S0040-4039(00)99313-4 |issn=0040-4039|url-access=subscription }}

Traditional catalytic aids such as phosphine ligands make the cobalt complex too stable, but bulky phosphite ligands are operable.

File:Sulfur_Additive.png

Lewis basic additives, such as n-BuSMe, are also believed to accelerate the decarbonylative ligand exchange process. However, an alternative view holds that the additives make olefin insertion irreversible instead.{{Cite journal |last1=Valle |first1=Carlos Perez del |last2=Milet |first2=Anne |last3=Gimbert |first3=Yves |last4=Greene |first4=Andrew E. |date=2005 |title=Lewis Base Promoters in the Pauson–Khand Reaction: A Different Scenario |url=https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.200500955 |journal=Angewandte Chemie International Edition |volume=44 |issue=35 |pages=5717–5719 |doi=10.1002/anie.200500955 |issn=1521-3773 |pmid=16078280|url-access=subscription }} Sulfur compounds are typically hard to handle and smelly, but n-dodecyl methyl sulfide{{Cite journal |last1=Cochrane |first1=Alison R. |last2=Kerr |first2=William J. |last3=Paterson |first3=Laura C. |last4=Pearson |first4=Colin M. |last5=Shaw |first5=Paul |date=2021-01-08 |title=Advances in the cobalt-catalysed Pauson-Khand reaction: Development of a sulfide-promoted, microwave-assisted protocol |url=https://www.sciencedirect.com/science/article/abs/pii/S0040402020310486 |journal=Tetrahedron |language=en |volume=78 |pages=131805 |doi=10.1016/j.tet.2020.131805 |issn=0040-4020 |s2cid=229387356|url-access=subscription }} and tetramethylthiourea{{Cite journal |last1=Reuter |first1=Carin |last2=Vögtle |first2=Fritz |date=March 2000 |title=Rotaxanes via Michael Addition† |url=http://dx.doi.org/10.1021/ol990350u |journal=Organic Letters |volume=2 |issue=5 |pages=593–595 |doi=10.1021/ol990350u |issn=1523-7060 |pmid=10814386|url-access=subscription }} do not suffer from those problems and can improve reaction performance.

The two most common amine N-oxides are N-methylmorpholine N-oxide (NMO) and trimethylamine N-oxide (TMANO). It is believed that these additives remove carbon monoxide ligands via nucleophilic attack of the N-oxide onto the CO carbonyl, oxidizing the CO into CO₂, and generating an unsaturated organometallic complex.{{Cite journal |last1=Shambayani |first1=Soroosh |last2=Crowe |first2=William E. |last3=Schreiber |first3=Stuart L. |date=1990-01-01 |title=N-oxide promoted pauson-khand cyclizations at room temperature |url=https://www.sciencedirect.com/science/article/abs/pii/S0040403900980523 |journal=Tetrahedron Letters |language=en |volume=31 |issue=37 |pages=5289–5292 |doi=10.1016/S0040-4039(00)98052-3 |issn=0040-4039|url-access=subscription }}{{Cite journal |last1=Alper |first1=Howard |last2=Edward |first2=J. T. |date=2011-02-03 |title=Reactions of iron pentacarbonyl with compounds containing the N—O linkage |journal=Canadian Journal of Chemistry |language=en |volume=48 |issue=10 |pages=1543–1549 |doi=10.1139/v70-251|doi-access=free }} This renders the first step of the mechanism irreversible, and allows for more mild conditions. Hydrates of the aforementioned amine N-oxides have similar effect.{{Cite journal |last1=Crawford |first1=James J. |last2=Kerr |first2=William J. |last3=McLaughlin |first3=Mark |last4=Morrison |first4=Angus J. |last5=Pauson |first5=Peter L. |last6=Thurston |first6=Graeme J. |date=2006-12-04 |title=Use of a highly effective intramolecular Pauson–Khand cyclisation for the formal total synthesis of (±)-α- and β-cedrene by preparation of cedrone |url=https://www.sciencedirect.com/science/article/abs/pii/S0040402006008192 |journal=Tetrahedron |language=en |volume=62 |issue=49 |pages=11360–11370 |doi=10.1016/j.tet.2006.05.044 |issn=0040-4020|url-access=subscription }}{{Cite journal |last1=Krafft |first1=Marie E. |last2=Romero |first2=Romulo H. |last3=Scott |first3=Ian L. |date=1992-09-01 |title=Pauson-Khand reaction with electron-deficient alkynes |url=https://doi.org/10.1021/jo00046a001 |journal=The Journal of Organic Chemistry |volume=57 |issue=20 |pages=5277–5278 |doi=10.1021/jo00046a001 |issn=0022-3263|url-access=subscription }}{{Cite journal |last1=Bernardes |first1=Vania |last2=Kann |first2=Nina |last3=Riera |first3=Antoni |last4=Moyano |first4=Albert |last5=Pericas |first5=Miquel A. |last6=Greene |first6=Andrew E. |date=1995-10-01 |title=Asymmetric Pauson-Khand Cyclization: A Formal Total Synthesis of Natural Brefeldin A |url=https://doi.org/10.1021/jo00126a010 |journal=The Journal of Organic Chemistry |volume=60 |issue=21 |pages=6670–6671 |doi=10.1021/jo00126a010 |issn=0022-3263|url-access=subscription }}

File:Additives.png, DCM = dichloromethane]]

N-oxide additives can also improve enantio- and diastereoselectivity, although the mechanism thereby is not clear.{{Cite journal |last1=Jamison |first1=Timothy F. |last2=Shambayati |first2=Soroosh |last3=Crowe |first3=William E. |last4=Schreiber |first4=Stuart L. |date=1997-05-01 |title=Tandem Use of Cobalt-Mediated Reactions to Synthesize (+)-Epoxydictymene, a Diterpene Containing a Trans-Fused 5−5 Ring System |url=https://doi.org/10.1021/ja970022u |journal=Journal of the American Chemical Society |volume=119 |issue=19 |pages=4353–4363 |doi=10.1021/ja970022u |issn=0002-7863|url-access=subscription }}{{Cite journal |last1=Carbery |first1=David R. |last2=Kerr |first2=William J. |last3=Lindsay |first3=David M. |last4=Scott |first4=James S. |last5=Watson |first5=Stephen P. |date=2000-04-22 |title=Preparation and reaction of desymmetrised cobalt alkyne complexes |url=https://www.sciencedirect.com/science/article/abs/pii/S0040403900003567 |journal=Tetrahedron Letters |language=en |volume=41 |issue=17 |pages=3235–3239 |doi=10.1016/S0040-4039(00)00356-7 |issn=0040-4039|url-access=subscription }}{{Cite journal |last1=Jończyk |first1=Andrzej |last2=Konarska |first2=Anna |date=July 1999 |title=Generation and Reactions of Ammonium Ylides in Basic Two-Phase Systems: Convenient Synthesis of Cyclopropanes, Oxiranes and Alkenes Substituted with Electron-Withdrawing Groups |url=http://www.thieme-connect.de/DOI/DOI?10.1055/s-1999-2757 |journal=Synlett |language=en |volume=1999 |issue=7 |pages=1085–1087 |doi=10.1055/s-1999-2757 |s2cid=196781210 |issn=0936-5214|url-access=subscription }}

File:Screiber_example.png, DCM = dichloromethane)

A step in the total synthesis of epoxydictymene: temperature and ultrasound failed to improve the d.r. for the desired diastereomer (the red hydrogen). But the N-oxide additive, while lower yielding, gave a d.r. of 11:1. ]]

(Co)₄(CO)₁₂ and Co₃(CO)₉(μ³-CH) also catalyze the PK reaction{{Cite journal |last1=Kim |first1=Jong Wook |last2=Chung |first2=Young Keun |date=February 1998 |title=Pauson-Khand Reaction Catalyzed by Co4(CO)12 |url=http://dx.doi.org/10.1055/s-1998-2016 |journal=Synthesis |volume=1998 |issue=2 |pages=142–144 |doi=10.1055/s-1998-2016 |s2cid=196736582 |issn=0039-7881|url-access=subscription }}{{Cite journal |last1=Sugihara |first1=Takumichi |last2=Yamaguchi |first2=Masahiko |date=1998-10-01 |title=The Pauson−Khand Reaction Catalyzed by the Methylidynetricobalt Nonacarbonyl Cluster |url=http://dx.doi.org/10.1021/ja982635s |journal=Journal of the American Chemical Society |volume=120 |issue=41 |pages=10782–10783 |doi=10.1021/ja982635s |issn=0002-7863|url-access=subscription }} although Takayama et al detail a reaction catalyzed by dicobalt octacarbonyl.{{cite journal |last1=Nakayama |first1=Atsushi |last2=Kogure |first2=Noriyuki |last3=Kitajima |first3=Mariko |last4=Takayama |first4=Hiromitsu |year=2011 |title=Asymmetric Total Synthesis of a Pentacyclic Lycopodium Alkaloid: Huperzine-Q |journal=Angew. Chem. Int. Ed. |volume=50 |issue=35 |pages=8025–8028 |doi=10.1002/anie.201103550 |pmid=21751323 |s2cid=10947595}}

File:Syn_ex.png total synthesis of the Lycopodium alkaloid huperzine-Q: Co₂(CO)₈ catalyzes an enyne cyclization. The siloxane ring ensures{{cite book |last=Ho |first=Tse-Lok |title=Fiesers' Reagents for Organic Synthesis |publisher=John Wiley & Sons |year=2016 |isbn=9781118942819 |volume=28 |pages=251–252 |chapter=Dicobalt Octacarbonyl |chapter-url=https://books.google.com/books?id=AO3bCwAAQBAJ&pg=PA251}} that only a single product enantiomer forms.]]

One stabilization method is to generate the catalyst in situ. Chung reports that Co(acac)₂ can serve as a precatalyst, activated by sodium borohydride.{{Cite journal |last1=Lee |first1=Nam Young |last2=Chung |first2=Young Keun |date=April 1996 |title=Synthesis of cyclopentenones: The new catalytic cocyclization reaction of alkyne, alkene, and carbon monoxide employing catalytic Co(acac)2 and NaBH4 |url=http://dx.doi.org/10.1016/0040-4039(96)00513-8 |journal=Tetrahedron Letters |volume=37 |issue=18 |pages=3145–3148 |doi=10.1016/0040-4039(96)00513-8 |issn=0040-4039|url-access=subscription }}

catalyst requires a silver triflate co-catalyst to effect the Pauson–Khand reaction: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. ([http://www.iupac.org/publications/pac/2002/pdf/7401x0085.pdf Online article])

File:Ex_1_var.png

Molybdenum hexacarbonyl is a carbon monoxide donor in PK-type reactions between allenes and alkynes with dimethyl sulfoxide in toluene.{{cite journal |last1=Kent |first1=J |year=1995 |title=A new allenic Pauson-Khand cycloaddition for the preparation of α-methylene cyclopentenones |journal=Tetrahedron Letters |volume=36 |issue=14 |pages=2407–2410 |doi=10.1016/0040-4039(95)00315-4}} Titanium, nickel,Titanium:

• {{Cite journal |last1=Hicks |first1=Frederick A. |last2=Buchwald |first2=Stephen L. |date=1996-01-01 |title=Highly Enantioselective Catalytic Pauson−Khand Type Formation of Bicyclic Cyclopentenones |url=http://dx.doi.org/10.1021/ja9630452 |journal=Journal of the American Chemical Society |volume=118 |issue=46 |pages=11688–11689 |doi=10.1021/ja9630452 |issn=0002-7863|url-access=subscription }}
• {{Cite journal |last1=Hicks |first1=Frederick A. |last2=Kablaoui |first2=Natasha M. |last3=Buchwald |first3=Stephen L. |date=January 1996 |title=Titanocene-Catalyzed Cyclocarbonylation of Enynes to Cyclopentenones |url=http://dx.doi.org/10.1021/ja9621509 |journal=Journal of the American Chemical Society |volume=118 |issue=39 |pages=9450–9451 |doi=10.1021/ja9621509 |issn=0002-7863|url-access=subscription }}

Nickel:

• {{Cite journal |last1=Zhang |first1=Minghui |last2=Buchwald |first2=Stephen L. |date=January 1996 |title=A Nickel(0)-Catalyzed Process for the Transformation of Enynes to Bicyclic Cyclopentenones |url=http://dx.doi.org/10.1021/jo960410z |journal=The Journal of Organic Chemistry |volume=61 |issue=14 |pages=4498–4499 |doi=10.1021/jo960410z |issn=0022-3263 |pmid=11667365|url-access=subscription }} and zirconium
• {{Cite journal |last1=Negishi |first1=Eiichi |last2=Holmes |first2=Steven J. |last3=Tour |first3=James M. |last4=Miller |first4=Joseph A. |date=1985-04-01 |title=Metal promoted cyclization. 7. Zirconium-promoted bicyclization of enynes |url=https://doi.org/10.1021/ja00294a071 |journal=Journal of the American Chemical Society |volume=107 |issue=8 |pages=2568–2569 |doi=10.1021/ja00294a071 |issn=0002-7863|url-access=subscription }}
• {{Cite journal |last1=Negishi |first1=Eiichi |last2=Holmes |first2=Steven J. |last3=Tour |first3=James M. |last4=Miller |first4=Joseph A. |last5=Cederbaum |first5=Fredrik E. |last6=Swanson |first6=Douglas R. |last7=Takahashi |first7=Tamotsu |date=April 1989 |title=Metal-promoted cyclization. 19. Novel bicyclization of enynes and diynes promoted by zirconocene derivatives and conversion of zirconabicycles into bicyclic enones via carbonylation |url=http://dx.doi.org/10.1021/ja00191a035 |journal=Journal of the American Chemical Society |volume=111 |issue=9 |pages=3336–3346 |doi=10.1021/ja00191a035 |issn=0002-7863|url-access=subscription }} complexes admit the reaction. Other metals can also be employed in these transformations.{{Cite journal |last1=Jeong |first1=Nakcheol |last2=Hwang |first2=Sung Hee |last3=Lee |first3=Youngshin |last4=Chung |first4=Young Keun |date=April 1994 |title=Catalytic version of the Intramolecular Pauson-Khand Reaction |url=http://dx.doi.org/10.1021/ja00086a070 |journal=Journal of the American Chemical Society |volume=116 |issue=7 |pages=3159–3160 |doi=10.1021/ja00086a070 |issn=0002-7863|url-access=subscription }}{{sfn|Ríos Torres|2012}}

In general allenes, support the Pauson–Khand reaction; regioselectivity is determined by the choice of metal catalyst. Density functional investigations show the variation arises from different transition state metal geometries.{{Cite journal |last1=Bayden |first1=Alexander S. |last2=Brummond |first2=Kay M. |author-link2=Kay Brummond |last3=Jordan |first3=Kenneth D. |date=2006-10-01 |title=Computational Insight Concerning Catalytic Decision Points of the Transition Metal Catalyzed [2 + 2 + 1] Cyclocarbonylation Reaction of Allenes |url=https://doi.org/10.1021/om0607503 |journal=Organometallics |volume=25 |issue=22 |pages=5204–5206 |doi=10.1021/om0607503 |issn=0276-7333 |pmc=4441411 |pmid=26005240}}

File:Allene_ex.png

Heteroatoms are also acceptable: Mukai et al's total synthesis of physostigmine applied the Pauson–Khand reaction to a carbodiimide.{{Cite journal |last1=Mukai |first1=Chisato |last2=Yoshida |first2=Tatsunori |last3=Sorimachi |first3=Mao |last4=Odani |first4=Akira |date=January 2006 |title=Co₂(CO)₈-Catalyzed Intramolecular Hetero-Pauson−Khand Reaction of Alkynecarbodiimide: Synthesis of (±)-Physostigmine |url=http://dx.doi.org/10.1021/ol052562z |journal=Organic Letters |volume=8 |issue=1 |pages=83–86 |doi=10.1021/ol052562z |issn=1523-7060 |pmid=16381573|url-access=subscription }}

File:Physostigmine_.png

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

File:Can_ex.png

An example of a newer version is the use of the chlorodicarbonylrhodium(I) dimer, [(CO)₂RhCl]₂, in the synthesis of (+)-phorbol by Phil Baran. 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.{{cite journal |last1=Kawamura |first1=Shuhei |last2=Chu |first2=Hang |last3=Felding |first3=Jakob |last4=Baran |first4=Phil S. |author-link4=Phil S. Baran |year=2016 |title=Nineteen-step total synthesis of (+)-phorbol |journal=Nature |volume=532 |issue=7597 |pages=90–93 |bibcode=2016Natur.532...90K |doi=10.1038/nature17153 |pmc=4833603 |pmid=27007853}}

The cyclopentenone motif can be prepared from aldehydes, carboxylic acids, and formates. These examples typically employ rhodium as the catalyst, as it is commonly used in decarbonylation reactions. The decarbonylation and PK reaction occur in the same reaction vessel.{{Cite journal |last1=Morimoto |first1=Tsumoru |last2=Fuji |first2=Koji |last3=Tsutsumi |first3=Ken |last4=Kakiuchi |first4=Kiyomi |date=2002 |title=CO-Transfer Carbonylation Reactions. A Catalytic Pauson−Khand-Type Reaction of Enynes with Aldehydes as a Source of Carbon Monoxide |journal=Journal of the American Chemical Society |volume=124 |issue=15 |pages=3806–3807 |doi=10.1021/ja0126881|pmid=11942798 }}{{Cite journal |last1=Shibata |first1=Takanori |last2=Toshida |first2=Natsuko |last3=Takagi |first3=Kentaro |date=2002 |title= Catalytic Pauson−Khand-Type Reaction Using Aldehydes as a CO Source |journal=Organic Letters |volume=4 |issue=9 |pages= 1619–1621 |doi=10.1021/ol025836g|pmid=11975643 }}

• Nicholas reaction

For Khand and Pauson's perspective on the reaction:

• {{Cite journal |last1=Khand |first1=Ihsan U. |last2=Knox |first2=Graham R. |last3=Pauson |first3=Peter L. |author-link3=Peter Pauson |last4=Watts |first4=William E. |date=1973a |title=Organocobalt complexes, Part I: Arene complexes derived from dodecacarbonyl­tetracobalt |journal=Journal of the Chemical Society, Perkin Transactions |issue=1 |pages=975–977 |doi=10.1039/p19730000975 |issn=0300-922X}}
• {{Cite journal |last1=Khand |first1=Ihsan U. |last2=Knox |first2=Graham R. |last3=Pauson |first3=Peter L. |author-link3=Peter Pauson |last4=Watts |first4=William E. |last5=Foreman |first5=Michael I. |date=1973b |title=Organocobalt complexes, Part II: Reaction of acetylene­hexacarbonyl­dicobalt complexes, (R¹C₂R²)Co₂(CO)₆, with norbornene and its derivatives |journal=Journal of the Chemical Society, Perkin Transactions |language=en |issue=1 |pages=977–981 |doi=10.1039/p19730000977 |issn=0300-922X}}
• {{cite journal |last1=Pauson |first1=P. L. |author-link1=Peter Pauson |last2=Khand |first2=I. U. |year=1977 |title=Uses of Cobalt-Carbonyl Acetylene Complexes in Organic Synthesis |journal=Ann. N. Y. Acad. Sci. |volume=295 |issue=1 |pages=2–14 |bibcode=1977NYASA.295....2P |doi=10.1111/j.1749-6632.1977.tb41819.x |s2cid=84203764}}

For a modern perspective:

• {{Cite book |last=Hartwig |first=John F. |title=Organotransition Metal Chemistry: from bonding to catalysis |date=2010 |publisher=University Science Books |isbn=978-1-891389-53-5 |location=Mill Valley, Calif. |oclc=310401036 |via=Knovel}}
• {{Cite book |last=Ríos Torres |first=Ramón |title=The Pauson-Khand reaction : scope, variations, and applications |date=2012 |publisher=John Wiley & Sons |isbn=978-1-118-30863-9 |editor-last1=Rios Torres |editor-first1=Ramon |location=Hoboken, N.J. |doi=10.1002/9781119941934 |oclc=774982574}}
• {{cite journal |last1=Gibson |first1=Susan E. |last2=Stevenazzi |first2=Andrea |year=2003 |title=The Pauson–Khand Reaction: The Catalytic Age Is Here! |journal=Angew. Chem. Int. Ed. |volume=42 |issue=16 |pages=1800–1810 |doi=10.1002/anie.200200547 |pmid=12722067}}
• {{cite book|last1=Buchwald|first1=Stephen L.|last2=Hicks|first2=Frederick A.|year=1999|chapter=Pauson–Khand-type reactions|editor-last1=Jacobsen|editor-first1=Eric N.|editor-last2=Pfaltz|editor-first2=Andreas|editor3=Yamamoto Hisashi|title=Comprehensive Asymmetric Catalysis|volume=II|location=Berlin|publisher=Springer|pages=491–513}}

{{Reflist|2}}

{{Alkynes}}

Category:Cycloadditions

Category:Multiple component reactions

Category:Name reactions