Aryne

In chemistry, an aryne is an uncharged reactive intermediate derived from an aromatic system by removal of two ortho substituents, leaving two orbitals with two electrons distributed between them.^{[1] [2]}. In analogy with carbenes and nitrenes, an aryne has a singlet state and a triplet state.

The simplest aryne, C₆H₄ (labeled 1 in the diagram to the right), is sometimes called benzyne. However, this name is open for criticism because it implies a triple bond which would be a special case of triple bonds, so a better name is didehydrobenzene. Benzyne is, like benzene, stabilized by resonance between structures 1 and 2— so, like the case of benzene, a better representation of the electronic structure would be 3. The "extra" pi bond (4b) is localised and orthogonal to the other pi bonds making up the aromatic ring (4a). Benzyne can also be drawn as a diradical: the pi bond 4b splits homolytically, leaving one electron on each of the two atoms that are formally part of that bond.^{[citation needed]}

Benzyne is an extremely reactive species due to the nature of its triple bond. In normal acetylenic species (such as the simplest, ethyne) the unhybridized p orbitals are parallel to one another above and below the molecular axis. This facilitates maximum orbital overlap. In benzyne, however, the p orbitals are distorted to accommodate the triple bond within the ring system, reducing their effective overlap. A suitable chemical trap for benzyne is a cyclopentadiene.

There are three possible diradical didehydrobenzenes: 1,2-didehydrobenzene, 1,3-didehydrobenzene and 1,4-didehydrobenzene. Their energies in silico are respectively 106, 122, and 138 kcal/mol (444, 510, and 577 kJ/mol).^[3] The 1,4-diradical species has been identified in the Bergman cyclization. Professor Maitland Jones of Princeton University has studied the interconversion of the 1,2-, 1,3- and 1,4-didehydrobenzenes.^[3][4]

Arynes were first postulated by Wittig in 1940 ^{[5] [6] [7]} and by Roberts in 1953 ^{[8] [9] [10] [11] [12]}

Aryne chemistry

Arynes are often prepared from aryl halides in presence of a strong base. The most prominent aryne reactions are Diels-Alder reactions with dienes. A classic example is the synthesis of 1,2,3,4-tetraphenylnaphthalene. Tetrabromobenzene reacts with butyllithium and furan to form a tetrahydroanthracene ^[13]. The mixture of syn and anti stereoisomers can be separated based on difference in methanol solubility.

Anthracene is converted to a triptycene by Diels-Alder reaction of an aryne with the central benzene ring ^[14]. A pentiptycene is the anthracene analogue after the reaction with 1,2,4,5-tetrabromobenzene and butyllithium.

Aryne reactivity can also be extended to carbon insertion reactions into substrates that can react both as a nucleophile and as an electrophile with for instance a malonic acid ester ^[15]. The precursor of benzyne in this reaction is 2-(trimethylsilyl)phenyl triflate.

Didehydrobenzene interconversions

A 1,2- to 1,3-didehydrobenzene conversion has been postulated to occur in the pyrolysis (900°C) of the phenyl substituted aryne precursor 1 ^[3] to acenaphthylene 7.

This reaction takes place through several reactive intermediates: the aryne 2 is formed from phenyl substituted phthalic anhydride which rearranges with ring contraction to the vinylidene 3. This carbene gives a C-H insertion reaction to pentalene 4 and then an extrusion to vinylidene 5. After cis-trans isomerisation to 6 a final insertion reaction gives the acenaphthylene. Evidence for a phenyl migration in aryne 2 from the 1,2-didehydrobenzene to the 1,3-didehydrobenzene is based on isotope scrambling. When the ipso carbon atom is replaced by ¹³C in the precursor molecule it will in the default mechanism again show up in the acenaphthylene in an ipso arene position. The presence of ¹³C in the bridge position can only be explained when 15% of 2 isomerizes to 1,3-didehydrobenzene A.

Scope

Aryne chemistry has been applied to the synthesis of novel aryl amines in a tandem reaction including two Diels-Alder reactions with three benzyne molecules reacting to one imidazole molecule ^[16]:

2-(trimethylsilyl)phenyl triflate as aryne precursor is a mild method for aryne generation and this process have been widely used in organic synthesis. For example, since the seminal work of Guitiàn, Perez and co-workers, it has been established that arynes participate in palladium-catalyzed processes ^[17]. Their very high reactivity can help to trap very unstable Pd species. As an example, azapalladium(II) complexes resulting from the oxidative addition of an acyloxime to Pd0 can undergo aminopalladation of aryne and subsequently a C-H activation process to give access to biologically relevant phenanthridines and isoquinolines^[18]:

See also

• More examples use of aryne chemistry: tricyclobutabenzene, in-methylcyclophane

References

1. ^ Gilchrist T.C.; Rees C.W.; (1969) Carbenes, Nitrenes and Arynes Nelson. London.
2. ^ The Benzyne and Related Intermediates. H. Heaney Chem. Rev., 1962, 62 (2), pp 81–97 doi:10.1021/cr60216a001
3. ^ ^{a b c} A m-Benzyne to o-Benzyne Conversion Through a 1,2-Shift of a Phenyl Group. Blake, M. E.; Bartlett, K. L.; Jones, M. Jr. J. Am. Chem. Soc. 2003, 125, 6485. doi:10.1021/ja0213672
4. ^ A p-Benzyne to m-Benzyne Conversion Through a 1,2-Shift of a Phenyl Group. Completion of the Benzyne Cascade, Polishchuk, A. L.; Bartlett, K. L.; Friedman, L. A.; Jones, M. Jr. J. Phys. Org. Chem. 2004, Volume 17, Issue 9 , Pages 798 - 806. doi:10.1002/poc.797
5. ^ Wittig, G., Pieper, G. and Fuhrmann, G. (1940), Über die Bildung von Diphenyl aus Fluorbenzol und Phenyl-lithium (IV. Mitteil. über Austauschreaktionen mit Phenyl-lithium). Berichte der deutschen chemischen Gesellschaft (A and B Series), 73: 1193–1197. doi:10.1002/cber.19400731113
6. ^ Phenyl-lithium, der Schlüssel zu einer neuen Chemie metallorganischer Verbindungen Georg Wittig Naturwissenschaften, 1942, Volume 30, Numbers 46-47, Pages 696-703 doi:10.1007/BF01489519
7. ^ Wittig, G. (1954), Fortschritte auf dem Gebiet der organischen Aniono-Chemie. Angewandte Chemie, 66: 10–17. doi:10.1002/ange.19540660103
8. ^ REARRANGEMENT IN THE REACTION OF CHLOROBENZENE-1-C14 WITH POTASSIUM AMIDE John D. Roberts, Howard E. Simmons Jr., L. A. Carlsmith, C. Wheaton Vaughan J. Am. Chem. Soc., 1953, 75 (13), pp 3290–3291 doi: 10.1021/ja01109a523
9. ^ The Mechanism of Aminations of Halobenzenes John D. Roberts, Dorothy A. Semenow, Howard E. Simmons Jr., L. A. Carlsmith J. Am. Chem. Soc., 1956, 78 (3), pp 601–611 doi:10.1021/ja01584a024
10. ^ Orientation in Aminations of Substituted Halobenzenes John D. Roberts, C. Wheaton Vaughan, L. A. Carlsmith, Dorothy A. Semenow J. Am. Chem. Soc., 1956, 78 (3), pp 611–614 doi:10.1021/ja01584a025
11. ^ Modern Arylation Methods. Edited by Lutz Ackermann 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN 978-3-527-31937-4
12. ^ The Benzyne and Related Intermediates. H. Heaney Chem. Rev., 1962, 62 (2), pp 81–97 doi:10.1021/cr60216a001
13. ^ Organic Syntheses, Coll. Vol. 10, p.678; Vol. 75, p.201 Article
14. ^ Iptycenes, cuppedophanes and cappedophanes Harold Hart Pure & App Chem, Vol. 65, No. 1, pp. 27-34, 1993. Article
15. ^ Facile insertion reaction of arynes into carbon–carbon -bonds Hiroto Yoshida, Masahiko Watanabe, Joji Ohshita and Atsutaka Kunai, Chem. Commun., 2005, (26), 3292 Abstract
16. ^ A New Tandem Reaction of Benzyne: One-Pot Synthesis of Aryl Amines Containing Anthracene Chunsong Xie and Yuhong Zhang Org. Lett.; 2007; 9(5) pp 781 - 784; (Letter) doi:10.1021/ol063017g
17. ^ D. Peña, S. Escudero, D. Pérez, E. Guitián, L. Castedo, Angew. Chem. Int. Ed. 1998, 37, 2659-2661
18. ^ "Palladium-Catalyzed Annulation of Acyloximes with Arynes (or Alkynes) Synthesis of Phenanthridines and Isoquinolines", T. Gerfaud, L. Neuville and J. Zhu, Angew. Chem. Int. Ed.; 2009; 48, 572-577; doi:10.1002/anie.200804683