Cross-coupling reaction

Chemical reaction in which two molecules are joined due to a metal catalyst

In organic chemistry, a cross-coupling reaction is a reaction where two different fragments are joined. Cross-couplings are a subset of the more general coupling reactions. Often cross-coupling reactions require metal catalysts. One important reaction type is this:

R−M + R'−X → R−R' + MX (R, R' = organic fragments, usually aryl; M = main group center such as Li or MgX; X = halide)

These reactions are used to form carbon–carbon bonds but also carbon-heteroatom bonds.[1][2][3][4] Cross-coupling reaction are a subset of coupling reactions.

Richard F. Heck, Ei-ichi Negishi, and Akira Suzuki were awarded the 2010 Nobel Prize in Chemistry for developing palladium-catalyzed coupling reactions.[5][6]

## Mechanism

[edit]

Many mechanisms exist reflecting the myriad types of cross-couplings, including those that do not require metal catalysts.[7] Often, however, cross-coupling refers to a metal-catalyzed reaction of a nucleophilic partner with an electrophilic partner.

Mechanism proposed for Kumada coupling (L = Ligand, Ar = Aryl).

In such cases, the mechanism generally involves reductive elimination of R-R' from LnMR(R') (L = spectator ligand). This intermediate LnMR(R') is formed in a two step process from a low valence precursor LnM. The oxidative addition of an organic halide (RX) to LnM gives LnMR(X). Subsequently, the second partner undergoes transmetallation with a source of R'−. The final step is reductive elimination of the two coupling fragments to regenerate the catalyst and give the organic product. Unsaturated substrates, such as C(sp)−X and C(sp2)−X bonds, couple more easily, in part because they add readily to the catalyst.

### Catalysts

[edit]

Mechanism proposed for the Sonogashira coupling.

Catalysts are often based on palladium, which is frequently selected due to high functional group tolerance. Organopalladium compounds are generally stable towards water and air. Palladium catalysts can be problematic for the pharmaceutical industry, which faces extensive regulation regarding heavy metals. Many pharmaceutical chemists attempt to use coupling reactions early in production to minimize metal traces in the product.[8] Heterogeneous catalysts based on Pd are also well developed.[9]

Copper-based catalysts are also common, especially for coupling involving heteroatom-C bonds.[10][11]

Iron-,[12] cobalt-,[13] and nickel-based[14] catalysts have been investigated.

### Leaving groups

[edit]

The leaving group X in the organic partner is usually a halide, although triflate, tosylate, pivalate esters, and other pseudohalides have been used.[15] Chloride is an ideal group due to the low cost of organochlorine compounds. Frequently, however, C–Cl bonds are too inert, and bromide or iodide leaving groups are required for acceptable rates. The main group metal in the organometallic partner usually is an electropositive element such as tin, zinc, silicon, or boron.

## Carbon–carbon cross-coupling

[edit]

Many cross-couplings entail forming carbon–carbon bonds.

Reaction | Year  | Reactant A  | Reactant B | Catalyst | Remark

|
|
|
|
|

Cadiot–Chodkiewicz coupling | 1957 | RC≡CH | sp | RC≡CX | sp | Cu | requires base
Castro–Stephens coupling | 1963 | RC≡CH | sp | Ar-X | sp2 | Cu |
Corey–House synthesis | 1967 | R2CuLi or RMgX | sp3 | R-X | sp2, sp3 | Cu  | Cu-catalyzed version by Kochi, 1971
Kumada coupling | 1972 | RMgBr | sp2, sp3 | R-X | sp2 | Pd or Ni or Fe |
Heck reaction | 1972 | alkene | sp2 | Ar-X | sp2 | Pd or Ni | requires base
Sonogashira coupling | 1975 | ArC≡CH | sp | R-X | sp3 sp2 | Pd and Cu | requires base
Negishi coupling | 1977 | R-Zn-X | sp3, sp2, sp | R-X | sp3 sp2 | Pd or Ni |
Stille cross coupling | 1978 | R-SnR3 | sp3, sp2, sp | R-X | sp3 sp2 | Pd or Ni |
Suzuki reaction | 1979 | R-B(OR)2 | sp2 | R-X | sp3 sp2 | Pd or Ni | requires base
Murahashi coupling[16] | 1979  | R-Li  | sp2, sp3 | R-X  | sp2 | Pd or Ru  |
Hiyama coupling | 1988 | R-SiR3 | sp2 | R-X | sp3 sp2 | Pd | requires base
Fukuyama coupling | 1998 | R-Zn-I | sp3 | RCO(SEt) | sp2 | Pd or Ni | see Liebeskind–Srogl coupling, gives ketones
Liebeskind–Srogl coupling | 2000 | R-B(OR)2 | sp3, sp2 | RCO(SEt) Ar-SMe | sp2 | Pd | requires CuTC, gives ketones
Cross dehydrogenative coupling | 2004 | R-H | sp, sp2, sp3 | R'-H | sp, sp2, sp3 | Cu, Fe, Pd etc. | requires oxidant or dehydrogenation
Decarboxylative cross-coupling | 2000s | R-CO2H | sp2 | R'-X | sp, sp2 | Cu, Pd | Requires little-to-no base

The restrictions on carbon atom geometry mainly inhibit β-hydride elimination when complexed to the catalyst.[17]

## Carbon–heteroatom coupling

[edit]

Many cross-couplings entail forming carbon–heteroatom bonds (heteroatom = S, N, O). A popular method is the Buchwald–Hartwig reaction:

The Buchwald–Hartwig reaction |  | (Eq.1)

|
|

Reaction | Year  | Reactant A  | Reactant B | Catalyst | Remark

|
|
|
|
|

Ullmann-type reaction | 1905  | ArO-MM, ArNH2,RS-M,NC-M | sp3 | Ar-X (X = OAr, N(H)Ar, SR, CN) | sp2 | Cu |
Buchwald–Hartwig reaction[18] | 1994 | R2N-H | sp3 | R-X | sp2 | Pd | N-C coupling,
second generation free amine
Chan–Lam coupling[19] | 1998 | Ar-B(OR)2 | sp2 | Ar-NH2 | sp2 | Cu |

## Miscellaneous reactions

[edit]

Palladium-catalyzes the cross-coupling of aryl halides with fluorinated arene. The process is unusual in that it involves C–H functionalisation at an electron deficient arene.[20]

## Applications

[edit]

Cross-coupling reactions are important for the production of pharmaceuticals,[4] examples being montelukast, eletriptan, naproxen, varenicline, and resveratrol.[21] with Suzuki coupling being most widely used.[22] Some polymers and monomers are also prepared in this way.[23]

## Reviews

[edit]

* Fortman, George C.; Nolan, Steven P. (2011). "N-Heterocyclic carbene (NHC) ligands and palladium in homogeneous cross-coupling catalysis: a perfect union". Chemical Society Reviews. 40 (10): 5151–69. doi:10.1039/c1cs15088j. PMID 21731956.
* Yin; Liebscher, Jürgen (2007). "Carbon−Carbon Coupling Reactions Catalyzed by Heterogeneous Palladium Catalysts". Chemical Reviews. 107 (1): 133–173. doi:10.1021/cr0505674. PMID 17212474. S2CID 36974481.
* Jana, Ranjan; Pathak, Tejas P.; Sigman, Matthew S. (2011). "Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions Using Alkyl-organometallics as Reaction Partners". Chemical Reviews. 111 (3): 1417–1492. doi:10.1021/cr100327p. PMC 3075866. PMID 21319862.
* Molnár, Árpád (2011). "Efficient, Selective, and Recyclable Palladium Catalysts in Carbon−Carbon Coupling Reactions". Chemical Reviews. 111 (3): 2251–2320. doi:10.1021/cr100355b. PMID 21391571.
* Miyaura, Norio; Suzuki, Akira (1995). "Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds". Chemical Reviews. 95 (7): 2457–2483. CiteSeerX 10.1.1.735.7660. doi:10.1021/cr00039a007.
* Roglans, Anna; Pla-Quintana, Anna; Moreno-Mañas, Marcial (2006). "Diazonium Salts as Substrates in Palladium-Catalyzed Cross-Coupling Reactions". Chemical Reviews. 106 (11): 4622–4643. doi:10.1021/cr0509861. PMID 17091930. S2CID 8128630.
* Korch, Katerina M.; Watson, Donald A. (2019). "Cross-Coupling of Heteroatomic Electrophiles". Chemical Reviews. 119 (13): 8192–8228. doi:10.1021/acs.chemrev.8b00628. PMC 6620169. PMID 31184483.
* Cahiez, Gérard; Moyeux, Alban (2010). "Cobalt-Catalyzed Cross-Coupling Reactions". Chemical Reviews. 110 (3): 1435–1462. doi:10.1021/cr9000786. PMID 20148539.
* Yi, Hong; Zhang, Guoting; Wang, Huamin; Huang, Zhiyuan; Wang, Jue; Singh, Atul K.; Lei, Aiwen (2017). "Recent Advances in Radical C–H Activation/Radical Cross-Coupling". Chemical Reviews. 117 (13): 9016–9085. doi:10.1021/acs.chemrev.6b00620. PMID 28639787.

## References

[edit]

1. ^ Korch, Katerina M.; Watson, Donald A. (2019). "Cross-Coupling of Heteroatomic Electrophiles". Chemical Reviews. 119 (13): 8192–8228. doi:10.1021/acs.chemrev.8b00628. PMC 6620169. PMID 31184483.
2. ^ Corbet, Jean-Pierre; Mignani, Gérard (2006). "Selected Patented Cross-Coupling Reaction Technologies". Chemical Reviews. 106 (7): 2651–2710. doi:10.1021/cr0505268. PMID 16836296.
3. ^ New Trends in Cross-Coupling: Theory and Applications Thomas Colacot (Editor) 2014 ISBN 978-1-84973-896-5
4. ^ a b King, A. O.; Yasuda, N. (2004). "Palladium-Catalyzed Cross-Coupling Reactions in the Synthesis of Pharmaceuticals". Organometallics in Process Chemistry. Topics in Organometallic Chemistry. Vol. 6\. Heidelberg: Springer. pp. 205–245. doi:10.1007/b94551. ISBN 978-3-540-01603-8.
5. ^ "The Nobel Prize in Chemistry 2010 - Richard F. Heck, Ei-ichi Negishi, Akira Suzuki". NobelPrize.org. 2010-10-06. Retrieved 2010-10-06.
6. ^ Johansson Seechurn, Carin C. C.; Kitching, Matthew O.; Colacot, Thomas J.; Snieckus, Victor (2012). "Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize". Angewandte Chemie International Edition. 51 (21): 5062–5085. doi:10.1002/anie.201107017. PMID 22573393. S2CID 20582425.
7. ^ Sun, Chang-Liang; Shi, Zhang-Jie (2014). "Transition-Metal-Free Coupling Reactions". Chemical Reviews. 114 (18): 9219–9280. doi:10.1021/cr400274j. PMID 25184859.
8. ^ Thayer, Ann (2005-09-05). "Removing Impurities". Chemical & Engineering News. Retrieved 2015-12-11.
9. ^ Yin, L.; Liebscher, J. (2007). "Carbon−Carbon Coupling Reactions Catalyzed by Heterogeneous Palladium Catalysts". Chemical Reviews. 107 (1): 133–173. doi:10.1021/cr0505674. PMID 17212474. S2CID 36974481.
10. ^ Corbet, Jean-Pierre; Mignani, Gérard (2006). "Selected Patented Cross-Coupling Reaction Technologies". Chemical Reviews. 106 (7): 2651–2710. doi:10.1021/cr0505268. PMID 16836296.
11. ^ Evano, Gwilherm; Blanchard, Nicolas; Toumi, Mathieu (2008). "Copper-Mediated Coupling Reactions and Their Applications in Natural Products and Designed Biomolecules Synthesis". Chemical Reviews. 108 (8): 3054–3131. doi:10.1021/cr8002505. PMID 18698737.
12. ^ Robin B. Bedford (2015). "How Low Does Iron Go? Chasing the Active Species in Fe-Catalyzed Cross-Coupling Reactions". Acc. Chem. Res. 48 (5): 1485–1493. doi:10.1021/acs.accounts.5b00042. PMID 25916260.
13. ^ Cahiez, GéRard; Moyeux, Alban (2010). "Cobalt-Catalyzed Cross-Coupling Reactions". Chemical Reviews. 110 (3): 1435–1462. doi:10.1021/cr9000786. PMID 20148539.
14. ^ Rosen, Brad M.; Quasdorf, Kyle W.; Wilson, Daniella A.; Zhang, Na; Resmerita, Ana-Maria; Garg, Neil K.; Percec, Virgil (2011). "Nickel-Catalyzed Cross-Couplings Involving Carbon−Oxygen Bonds". Chemical Reviews. 111 (3): 1346–1416. doi:10.1021/cr100259t. PMC 3055945. PMID 21133429.
15. ^ Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, p. 792, ISBN 978-0-471-72091-1
16. ^ Murahashi, Shunichi; Yamamura, Masaaki; Yanagisawa, Kenichi; Mita, Nobuaki; Kondo, Kaoru (1979). "Stereoselective synthesis of alkenes and alkenyl sulfides from alkenyl halides using palladium and ruthenium catalysts". The Journal of Organic Chemistry. 44 (14): 2408–2417. doi:10.1021/jo01328a016. ISSN 0022-3263.
17. ^ Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford UP: Oxford, U.K., 2012. pp. 1069-1102.
18. ^ Ruiz-Castillo, P.; Buchwald, S. L. (2016). "Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions". Chemical Reviews. 116 (19): 12564–12649. doi:10.1021/acs.chemrev.6b00512. PMC 5070552. PMID 27689804.
19. ^ Jennifer X. Qiao; Patrick Y.S. Lam (2011). "Recent Advances in Chan–Lam Coupling Reaction: Copper-Promoted C–Heteroatom Bond Cross-Coupling Reactions with Boronic Acids and Derivatives". In Dennis G. Hall (ed.). Boronic Acids: Preparation and Applications in Organic Synthesis, Medicine and Materials. Wiley-VCH. pp. 315–361. doi:10.1002/9783527639328.ch6. ISBN 9783527639328.
20. ^ M. Lafrance; C. N. Rowley; T. K. Woo; K. Fagnou (2006). "Catalytic Intermolecular Direct Arylation of Perfluorobenzenes". J. Am. Chem. Soc. 128 (27): 8754–8756. CiteSeerX 10.1.1.631.607. doi:10.1021/ja062509l. PMID 16819868.
21. ^ Cornils, Boy; Börner, Armin; Franke, Robert; Zhang, Baoxin; Wiebus, Ernst; Schmid, Klaus (2017). "Hydroformylation". Applied Homogeneous Catalysis with Organometallic Compounds. pp. 23–90. doi:10.1002/9783527651733.ch2. ISBN 9783527328970.
22. ^ Roughley, Stephen D.; Jordan, Allan M. (2011). "The Medicinal Chemist's Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates". Journal of Medicinal Chemistry. 54 (10): 3451–3479. doi:10.1021/jm200187y. PMID 21504168.
23. ^ Hartwig, J. F. Organotransition Metal Chemistry, from Bonding to Catalysis; University Science Books: New York, 2010. ISBN 1-891389-53-X

* v
* t
* e

Topics in organic reactions

* Addition reaction
* Elimination reaction
* Polymerization
* Reagents
* Rearrangement reaction
* Redox reaction
* Regioselectivity
* Stereoselectivity
* Stereospecificity
* Substitution reaction

* A value
* Alpha effect
* Annulene
* Anomeric effect
* Antiaromaticity
* Aromatic ring current
* Aromaticity
* Baird's rule
* Baker–Nathan effect
* Baldwin's rules
* Bema Hapothle
* Beta-silicon effect
* Bicycloaromaticity
* Bredt's rule
* Bürgi–Dunitz angle
* Catalytic resonance theory
* Charge remote fragmentation
* Charge-transfer complex
* Clar's rule
* Conformational isomerism
* Conjugated system
* Conrotatory and disrotatory
* Curtin–Hammett principle
* Dynamic binding (chemistry)
* Edwards equation
* Effective molarity
* Electromeric effect
* Electron-rich
* Electron-withdrawing group
* Electronic effect
* Electrophile
* Evelyn effect
* Flippin–Lodge angle
* Free-energy relationship
* Grunwald–Winstein equation
* Hammett acidity function
* Hammett equation
* George S. Hammond
* Hammond's postulate
* Homoaromaticity
* Hückel's rule
* Hyperconjugation
* Inductive effect
* Kinetic isotope effect
* LFER solvent coefficients (data page)
* Marcus theory
* Markovnikov's rule
* Möbius aromaticity
* Möbius–Hückel concept
* More O'Ferrall–Jencks plot
* Negative hyperconjugation
* Neighbouring group participation
* 2-Norbornyl cation
* Nucleophile
* Kennedy J. P. Orton
* Passive binding
* Phosphaethynolate
* Polar effect
* Polyfluorene
* Ring strain
* Σ-aromaticity
* Spherical aromaticity
* Spiroaromaticity
* Steric effects
* Superaromaticity
* Swain–Lupton equation
* Taft equation
* Thorpe–Ingold effect
* Vinylogy
* Walsh diagram
* Woodward–Hoffmann rules
* Woodward's rules
* Y-aromaticity
* Yukawa–Tsuno equation
* Zaitsev's rule
* Σ-bishomoaromaticity

List of organic reactions

Carbon-carbon
bond forming
reactions|

* Acetoacetic ester synthesis
* Acyloin condensation
* Aldol condensation
* Aldol reaction
* Alkane metathesis
* Alkyne metathesis
* Alkyne trimerisation
* Alkynylation
* Allan–Robinson reaction
* Arndt–Eistert reaction
* Auwers synthesis
* Aza-Baylis–Hillman reaction
* Barbier reaction
* Barton–Kellogg reaction
* Baylis–Hillman reaction
* Benary reaction
* Bergman cyclization
* Biginelli reaction
* Bingel reaction
* Blaise ketone synthesis
* Blaise reaction
* Blanc chloromethylation
* Bodroux–Chichibabin aldehyde synthesis
* Bouveault aldehyde synthesis
* Bucherer–Bergs reaction
* Buchner ring expansion
* Cadiot–Chodkiewicz coupling
* Carbonyl allylation
* Carbonyl olefin metathesis
* Castro–Stephens coupling
* Chan rearrangement
* Chan–Lam coupling
* Claisen condensation
* Claisen rearrangement
* Claisen-Schmidt condensation
* Combes quinoline synthesis
* Corey–Fuchs reaction
* Corey–House synthesis
* Coupling reaction
* Cross-coupling reaction
* Cross dehydrogenative coupling
* Cross-coupling partner
* Dakin–West reaction
* Darzens reaction
* Diels–Alder reaction
* Doebner reaction
* Wulff–Dötz reaction
* Ene reaction
* Enyne metathesis
* Ethenolysis
* Favorskii reaction
* Ferrier carbocyclization
* Friedel–Crafts reaction
* Fujimoto–Belleau reaction
* Fujiwara–Moritani reaction
* Fukuyama coupling
* Gabriel–Colman rearrangement
* Gattermann reaction
* Glaser coupling
* Grignard reaction
* Grignard reagent
* Hammick reaction
* Heck reaction
* Henry reaction
* Heterogeneous metal catalyzed cross-coupling
* High dilution principle
* Hiyama coupling
* Homologation reaction
* Horner–Wadsworth–Emmons reaction
* Hydrocyanation
* Hydrovinylation
* Hydroxymethylation
* Ivanov reaction
* Johnson–Corey–Chaykovsky reaction
* Julia olefination
* Julia–Kocienski olefination
* Kauffmann olefination
* Knoevenagel condensation
* Knorr pyrrole synthesis
* Kolbe–Schmitt reaction
* Kowalski ester homologation
* Kulinkovich reaction
* Kumada coupling
* Liebeskind–Srogl coupling
* Malonic ester synthesis
* Mannich reaction
* McMurry reaction
* Meerwein arylation
* Methylenation
* Michael reaction
* Minisci reaction
* Mizoroki-Heck vs. Reductive Heck
* Nef isocyanide reaction
* Nef synthesis
* Negishi coupling
* Nierenstein reaction
* Nitro-Mannich reaction
* Nozaki–Hiyama–Kishi reaction
* Olefin conversion technology
* Olefin metathesis
* Palladium–NHC complex
* Passerini reaction
* Peterson olefination
* Pfitzinger reaction
* Piancatelli rearrangement
* Pinacol coupling reaction
* Prins reaction
* Quelet reaction
* Ramberg–Bäcklund reaction
* Rauhut–Currier reaction
* Reformatsky reaction
* Reimer–Tiemann reaction
* Rieche formylation
* Ring-closing metathesis
* Robinson annulation
* Sakurai reaction
* Seyferth–Gilbert homologation
* Shapiro reaction
* Sonogashira coupling
* Stetter reaction
* Stille reaction
* Stollé synthesis
* Stork enamine alkylation
* Suzuki reaction
* Takai olefination
* Thermal rearrangement of aromatic hydrocarbons
* Thorpe reaction
* Ugi reaction
* Ullmann reaction
* Wagner-Jauregg reaction
* Weinreb ketone synthesis
* Wittig reaction
* Wurtz reaction
* Wurtz–Fittig reaction
* Zincke–Suhl reaction

| Homologation reactions|

* Arndt–Eistert reaction
* Hooker reaction
* Kiliani–Fischer synthesis
* Kowalski ester homologation
* Methoxymethylenetriphenylphosphorane
* Seyferth–Gilbert homologation
* Wittig reaction

|

Olefination reactions|

* Bamford–Stevens reaction
* Barton–Kellogg reaction
* Boord olefin synthesis
* Chugaev elimination
* Cope reaction
* Corey–Winter olefin synthesis
* Dehydrohalogenation
* Elimination reaction
* Grieco elimination
* Hofmann elimination
* Horner–Wadsworth–Emmons reaction
* Hydrazone iodination
* Julia olefination
* Julia–Kocienski olefination
* Kauffmann olefination
* McMurry reaction
* Peterson olefination
* Ramberg–Bäcklund reaction
* Shapiro reaction
* Takai olefination
* Wittig reaction

Carbon-heteroatom
bond forming
reactions|

* Azo coupling
* Bartoli indole synthesis
* Boudouard reaction
* Cadogan–Sundberg indole synthesis
* Diazonium compound
* Esterification
* Grignard reagent
* Haloform reaction
* Hegedus indole synthesis
* Hurd–Mori 1,2,3-thiadiazole synthesis
* Kharasch–Sosnovsky reaction
* Knorr pyrrole synthesis
* Leimgruber–Batcho indole synthesis
* Mukaiyama hydration
* Nenitzescu indole synthesis
* Oxymercuration reaction
* Reed reaction
* Schotten–Baumann reaction
* Ullmann condensation
* Williamson ether synthesis
* Yamaguchi esterification

Degradation
reactions|

* Barbier–Wieland degradation
* Bergmann degradation
* Edman degradation
* Emde degradation
* Gallagher–Hollander degradation
* Hofmann rearrangement
* Hooker reaction
* Isosaccharinic acid
* Marker degradation
* Ruff degradation
* Strecker degradation
* Von Braun amide degradation
* Weerman degradation
* Wohl degradation

Organic redox
reactions|

* Acyloin condensation
* Adkins–Peterson reaction
* Akabori amino-acid reaction
* Alcohol oxidation
* Algar–Flynn–Oyamada reaction
* Amide reduction
* Andrussow process
* Angeli–Rimini reaction
* Aromatization
* Autoxidation
* Baeyer–Villiger oxidation
* Barton–McCombie deoxygenation
* Bechamp reduction
* Benkeser reaction
* Bergmann degradation
* Birch reduction
* Bohn–Schmidt reaction
* Bosch reaction
* Bouveault–Blanc reduction
* Boyland–Sims oxidation
* Cannizzaro reaction
* Carbonyl reduction
* Clemmensen reduction
* Collins oxidation
* Corey–Itsuno reduction
* Corey–Kim oxidation
* Corey–Winter olefin synthesis
* Criegee oxidation
* Dakin oxidation
* Davis oxidation
* Deoxygenation
* Dess–Martin oxidation
* DNA oxidation
* Elbs persulfate oxidation
* Emde degradation
* Eschweiler–Clarke reaction
* Étard reaction
* Fischer–Tropsch process
* Fleming–Tamao oxidation
* Fukuyama reduction
* Ganem oxidation
* Glycol cleavage
* Griesbaum coozonolysis
* Grundmann aldehyde synthesis
* Haloform reaction
* Hydrogenation
* Hydrogenolysis
* Hydroxylation
* Jones oxidation
* Kiliani–Fischer synthesis
* Kolbe electrolysis
* Kornblum oxidation
* Kornblum–DeLaMare rearrangement
* Leuckart reaction
* Ley oxidation
* Lindgren oxidation
* Lipid peroxidation
* Lombardo methylenation
* Luche reduction
* Markó–Lam deoxygenation
* McFadyen–Stevens reaction
* Meerwein–Ponndorf–Verley reduction
* Methionine sulfoxide
* Miyaura borylation
* Mozingo reduction
* Noyori asymmetric hydrogenation
* Omega oxidation
* Oppenauer oxidation
* Oxygen rebound mechanism
* Ozonolysis
* Parikh–Doering oxidation
* Pinnick oxidation
* Prévost reaction
* Reduction of nitro compounds
* Reductive amination
* Riley oxidation
* Rosenmund reduction
* Rubottom oxidation
* Sabatier reaction
* Sarett oxidation
* Selenoxide elimination
* Shapiro reaction
* Sharpless asymmetric dihydroxylation
* Epoxidation of allylic alcohols
* Sharpless epoxidation
* Sharpless oxyamination
* Stahl oxidation
* Staudinger reaction
* Stephen aldehyde synthesis
* Swern oxidation
* Transfer hydrogenation
* Wacker process
* Wharton reaction
* Whiting reaction
* Wohl–Aue reaction
* Wolff–Kishner reduction
* Wolffenstein–Böters reaction
* Zinin reaction

Rearrangement
reactions|

* 1,2-rearrangement
* 1,2-Wittig rearrangement
* 2,3-sigmatropic rearrangement
* 2,3-Wittig rearrangement
* Achmatowicz reaction
* Alkyne zipper reaction
* Allen–Millar–Trippett rearrangement
* Allylic rearrangement
* Alpha-ketol rearrangement
* Amadori rearrangement
* Arndt–Eistert reaction
* Aza-Cope rearrangement
* Baker–Venkataraman rearrangement
* Bamberger rearrangement
* Banert cascade
* Beckmann rearrangement
* Benzilic acid rearrangement
* Bergman cyclization
* Bergmann degradation
* Boekelheide reaction
* Brook rearrangement
* Buchner ring expansion
* Carroll rearrangement
* Chan rearrangement
* Claisen rearrangement
* Cope rearrangement
* Corey–Fuchs reaction
* Cornforth rearrangement
* Criegee rearrangement
* Curtius rearrangement
* Demjanov rearrangement
* Di-π-methane rearrangement
* Dimroth rearrangement
* Divinylcyclopropane-cycloheptadiene rearrangement
* Dowd–Beckwith ring-expansion reaction
* Electrocyclic reaction
* Ene reaction
* Enyne metathesis
* Favorskii reaction
* Favorskii rearrangement
* Ferrier carbocyclization
* Ferrier rearrangement
* Fischer–Hepp rearrangement
* Fries rearrangement
* Fritsch–Buttenberg–Wiechell rearrangement
* Gabriel–Colman rearrangement
* Group transfer reaction
* Halogen dance rearrangement
* Hayashi rearrangement
* Hofmann rearrangement
* Hofmann–Martius rearrangement
* Ireland–Claisen rearrangement
* Jacobsen rearrangement
* Kornblum–DeLaMare rearrangement
* Kowalski ester homologation
* Lobry de Bruyn–Van Ekenstein transformation
* Lossen rearrangement
* McFadyen–Stevens reaction
* McLafferty rearrangement
* Meyer–Schuster rearrangement
* Mislow–Evans rearrangement
* Mumm rearrangement
* Myers allene synthesis
* Nazarov cyclization reaction
* Neber rearrangement
* Newman–Kwart rearrangement
* Overman rearrangement
* Oxy-Cope rearrangement
* Pericyclic reaction
* Piancatelli rearrangement
* Pinacol rearrangement
* Pummerer rearrangement
* Ramberg–Bäcklund reaction
* Ring expansion and contraction
* Ring-closing metathesis
* Rupe reaction
* Schmidt reaction
* Semipinacol rearrangement
* Seyferth–Gilbert homologation
* Sigmatropic reaction
* Skattebøl rearrangement
* Smiles rearrangement
* Sommelet–Hauser rearrangement
* Stevens rearrangement
* Stieglitz rearrangement
* Thermal rearrangement of aromatic hydrocarbons
* Tiffeneau–Demjanov rearrangement
* Vinylcyclopropane rearrangement
* Wagner–Meerwein rearrangement
* Wallach rearrangement
* Weerman degradation
* Westphalen–Lettré rearrangement
* Willgerodt rearrangement
* Wolff rearrangement

Ring forming
reactions|

* 1,3-Dipolar cycloaddition
* Annulation
* Azide-alkyne Huisgen cycloaddition
* Baeyer–Emmerling indole synthesis
* Bartoli indole synthesis
* Bergman cyclization
* Biginelli reaction
* Bischler–Möhlau indole synthesis
* Bischler–Napieralski reaction
* Blum–Ittah aziridine synthesis
* Bobbitt reaction
* Bohlmann–Rahtz pyridine synthesis
* Borsche–Drechsel cyclization
* Bucherer carbazole synthesis
* Bucherer–Bergs reaction
* Cadogan–Sundberg indole synthesis
* Camps quinoline synthesis
* Chichibabin pyridine synthesis
* Cook–Heilbron thiazole synthesis
* Cycloaddition
* Darzens reaction
* Davis–Beirut reaction
* De Kimpe aziridine synthesis
* Debus–Radziszewski imidazole synthesis
* Dieckmann condensation
* Diels–Alder reaction
* Feist–Benary synthesis
* Ferrario–Ackermann reaction
* Fiesselmann thiophene synthesis
* Fischer indole synthesis
* Fischer oxazole synthesis
* Friedländer synthesis
* Gewald reaction
* Graham reaction
* Hantzsch pyridine synthesis
* Hegedus indole synthesis
* Hemetsberger indole synthesis
* Hofmann–Löffler reaction
* Hurd–Mori 1,2,3-thiadiazole synthesis
* Iodolactonization
* Isay reaction
* Jacobsen epoxidation
* Johnson–Corey–Chaykovsky reaction
* Knorr pyrrole synthesis
* Knorr quinoline synthesis
* Kröhnke pyridine synthesis
* Kulinkovich reaction
* Larock indole synthesis
* Madelung synthesis
* Nazarov cyclization reaction
* Nenitzescu indole synthesis
* Niementowski quinazoline synthesis
* Niementowski quinoline synthesis
* Paal–Knorr synthesis
* Paternò–Büchi reaction
* Pechmann condensation
* Petrenko-Kritschenko piperidone synthesis
* Pictet–Spengler reaction
* Pomeranz–Fritsch reaction
* Prilezhaev reaction
* Pschorr cyclization
* Reissert indole synthesis
* Ring-closing metathesis
* Robinson annulation
* Sharpless epoxidation
* Simmons–Smith reaction
* Skraup reaction
* Urech hydantoin synthesis
* Van Leusen reaction
* Wenker synthesis

| Cycloaddition|

* 1,3-Dipolar cycloaddition
* 4+4 Photocycloaddition
* (4+3) cycloaddition
* 6+4 Cycloaddition
* Alkyne trimerisation
* Aza-Diels–Alder reaction
* Azide-alkyne Huisgen cycloaddition
* Bradsher cycloaddition
* Cheletropic reaction
* Conia-ene reaction
* Cyclopropanation
* Diazoalkane 1,3-dipolar cycloaddition
* Diels–Alder reaction
* Enone–alkene cycloadditions
* Hexadehydro Diels–Alder reaction
* Imine Diels–Alder reaction
* Intramolecular Diels–Alder cycloaddition
* Inverse electron-demand Diels–Alder reaction
* Ketene cycloaddition
* McCormack reaction
* Metal-centered cycloaddition reactions
* Nitrone-olefin (3+2) cycloaddition
* Oxo-Diels–Alder reaction
* Ozonolysis
* Pauson–Khand reaction
* Povarov reaction
* Prato reaction
* Retro-Diels–Alder reaction
* Staudinger synthesis
* Trimethylenemethane cycloaddition
* Vinylcyclopropane (5+2) cycloaddition
* Wagner-Jauregg reaction

|

Heterocycle forming reactions|

* Algar–Flynn–Oyamada reaction
* Allan–Robinson reaction
* Auwers synthesis
* Bamberger triazine synthesis
* Banert cascade
* Barton–Zard reaction
* Bernthsen acridine synthesis
* Bischler–Napieralski reaction
* Bobbitt reaction
* Boger pyridine synthesis
* Borsche–Drechsel cyclization
* Bucherer carbazole synthesis
* Bucherer–Bergs reaction
* Chichibabin pyridine synthesis
* Cook–Heilbron thiazole synthesis
* Diazoalkane 1,3-dipolar cycloaddition
* Einhorn–Brunner reaction
* Erlenmeyer–Plöchl azlactone and amino-acid synthesis
* Feist–Benary synthesis
* Fischer oxazole synthesis
* Gabriel–Colman rearrangement
* Gewald reaction
* Hantzsch ester
* Hantzsch pyridine synthesis
* Herz reaction
* Knorr pyrrole synthesis
* Kröhnke pyridine synthesis
* Lectka enantioselective beta-lactam synthesis
* Lehmstedt–Tanasescu reaction
* Niementowski quinazoline synthesis
* Nitrone-olefin (3+2) cycloaddition
* Paal–Knorr synthesis
* Pellizzari reaction
* Pictet–Spengler reaction
* Pomeranz–Fritsch reaction
* Prilezhaev reaction
* Robinson–Gabriel synthesis
* Stollé synthesis
* Urech hydantoin synthesis
* Wenker synthesis
* Wohl–Aue reaction

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