Inorganic chemistry, acycloaddition is achemical reaction in which "two or moreunsaturated molecules (or parts of the same molecule) combine with the formation of a cyclicadduct in which there is a net reduction of thebond multiplicity". The resulting reaction is acyclization reaction. Many but not all cycloadditions areconcerted and thuspericyclic.[1] Nonconcerted cycloadditions are not pericyclic.[2] As a class ofaddition reaction, cycloadditions permit carbon–carbon bond formation without the use of anucleophile orelectrophile.
Cycloadditions can be described using two systems of notation. An older but still common notation is based on the size of linear arrangements of atoms in the reactants. It usesparentheses:(i +j + …) where the variables are the numbers of linear atoms in each reactant. The product is a cycle of size(i +j + …). In this system, the standardDiels-Alder reaction is a (4 + 2)-cycloaddition, the1,3-dipolar cycloaddition is a (3 + 2)-cycloaddition andcyclopropanation of a carbene with an alkene a (2 + 1)-cycloaddition.[1]
A more recent, IUPAC-preferred notation, first introduced byWoodward andHoffmann, usessquare brackets to indicate the number ofelectrons, rather than carbon atoms, involved in the formation of the product. In the [i +j + ...] notation, the standard Diels-Alder reaction is a [4 + 2]-cycloaddition, while the 1,3-dipolar cycloaddition is also a [4 + 2]-cycloaddition.[1]
Thermal cycloadditions are those cycloadditions where the reactants are in the ground electronic state. They usually have (4n + 2) π electrons participating in the starting material, for some integern. These reactions occur for reasons oforbital symmetry in asuprafacial-suprafacial (syn/syn stereochemistry) in most cases. Very few examples ofantarafacial-antarafacial (anti/anti stereochemistry) reactions have also been reported. There are a few examples of thermal cycloadditions which have 4n π electrons (for example the [2 + 2]-cycloaddition). These proceed in a suprafacial-antarafacial sense (syn/anti stereochemistry), such as the cycloaddition reactions ofketene andallene derivatives, in which theorthogonal set ofp orbitals allows the reaction to proceed via a crossedtransition state. Due to the involvement of an orthogonal orbital, this is classified as a pseudopericyclic reaction, to which the Woodward-Hoffmann rules do not apply to. Strained alkenes liketrans-cycloheptene derivatives have also been reported to react in an antarafacial manner in [2 + 2]-cycloaddition reactions.
Doering (in a personal communication toWoodward) reported thatheptafulvalene and tetracyanoethylene can react in a suprafacial-antarafacial [14 + 2]-cycloaddition. However, this reaction was later found to be stepwise, as it also produced the Woodward-Hoffmann forbidden suprafacial-suprafacial product under kinetic conditions.[3]
Erden and Kaufmann had previously found that the cycloaddition of heptafulvalene and N-phenyltriazolinedione also gave both suprafacial-antarafacial and suprafacial-suprafacial products, consistent with the stepwise nature of the analogous tetracyanoethylene reaction.[4]
Cycloadditions in which 4n π electrons participate can also occur viaphotochemical activation. Here, one component has an electron promoted from theHOMO (π bonding) to theLUMO (π*antibonding). Orbital symmetry is then such that the reaction can proceed in a suprafacial-suprafacial manner. An example is theDeMayo reaction. Another example is shown below, the photochemical dimerization ofcinnamic acid.[5] The twotransalkenes react head-to-tail, and the isolatedisomers are calledtruxillic acids.
Supramolecular effects can influence these cycloadditions. The cycloaddition oftrans-1,2-bis(4-pyridyl)ethene is directed byresorcinol in thesolid-state in 100%yield.[6]
Some cycloadditions instead of π bonds operate through strainedcyclopropane rings, as these have significant π character. For example, an analog for the Diels-Alder reaction is thequadricyclane-DMAD reaction:
In the (i+j+...) cycloaddition notation i and j refer to the number of atoms involved in the cycloaddition. In this notation, a Diels-Alder reaction is a (4+2)cycloaddition and a 1,3-dipolar addition such as the first step inozonolysis is a (3+2)cycloaddition. TheIUPAC preferred notation however, with [i+j+...] takes electrons into account and not atoms. In this notation, the DA reaction and the dipolar reaction both become a [4+2]cycloaddition. The reaction betweennorbornadiene and an activatedalkyne is a [2+2+2]cycloaddition.
TheDiels-Alder reaction is perhaps the most important and commonly taught cycloaddition reaction. Formally it is a [4+2] cycloaddition reaction and exists in a huge range of forms, including theinverse electron-demand Diels–Alder reaction,hexadehydro Diels–Alder reaction and the relatedalkyne trimerisation. The reaction can also be run in reverse in theretro-Diels–Alder reaction.
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Reactions involving heteroatoms are known, including theaza-Diels–Alder reaction andoxo-Diels–Alder reaction.
TheHuisgen cycloaddition reaction is a (2+3)cycloaddition.
TheNitrone-olefin cycloaddition is a (3+2)cycloaddition.
Cheletropic reactions are a subclass of cycloadditions. The key distinguishing feature of cheletropic reactions is that on one of the reagents, both new bonds are being made to the same atom. The classic example is the reaction ofsulfur dioxide with adiene.
Other cycloaddition reactions exist:(4+3) cycloadditions,[6+4] cycloadditions,[2 + 2] photocycloadditions,metal-centered cycloaddition and[4+4] photocycloadditions
Cycloadditions often have metal-catalyzed and stepwiseradical analogs, however these are not strictly speaking pericyclic reactions. When in a cycloaddition charged or radical intermediates are involved or when the cycloaddition result is obtained in a series of reaction steps they are sometimes calledformal cycloadditions to make the distinction with true pericyclic cycloadditions.
One example of a formal [3+3]cycloaddition between a cyclicenone and anenamine catalyzed byn-butyllithium is aStork enamine /1,2-additioncascade reaction:[7]
![An intermolecular formal [3+3] cycloaddition between an cyclic iminium chloride and cyclopentenone.](/mt/?noimg=&dark=on&url=http%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3a3%252B3_cycloaddition_-_cyclic_iminium_to_cyclic_enone.svg)
Iron[pyridine(diimine)] catalysts contain a redox active ligand in which the central iron atom can coordinate with two simple, unfunctionalized olefin double bonds. The catalyst can be written as a resonance between a structure containing unpaired electrons with the central iron atom in the II oxidation state, and one in which the iron is in the 0 oxidation state. This gives it the flexibility to engage in binding the double bonds as they undergo a cyclization reaction, generating a cyclobutane structure via C-C reductive elimination; alternatively a cyclobutene structure may be produced by beta-hydrogen elimination. Efficiency of the reaction varies substantially depending on the alkenes used, but rational ligand design may permit expansion of the range of reactions that can be catalyzed.[8][9]
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