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Utente:Grasso Luigi/sanbox1/Riarrangiamento Wolff

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Il riarrangiamento di Wolff consiste nella conversione di un α-diazochetone in un chetene.[1][2] La reazione fu descritta da L. Wolff nel 1912.

Il riarrangiamento di Wolff
Il riarrangiamento di Wolff

Il processo è catalizzato dalla luce, dal calore o da un catalizzatore a base di metallo di transizione come l'ossido di argento. Viene liberato azoto gassoso con formazione di un carbene che si stabilizza subendo il riarrangiamento.

In un'applicazione elettrochimica è possibile fare avvenire il riarrangiamento di Wolff in una cella galvanica, facendo ridurre il catalizzatore Ag2O ad argento elementare in fase nano-dispersa.

Meccanismo della reazione

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Il percorso meccanico di tale reazione è stato soggetto a intenso dibattito, come spesso avviene ci sono due meccanismi concorrenti quello concertato e quello graduale. [3] Tuttavia, due aspetti del meccanismo sono certi. (1) i composti α-diazocarbonili sono in equilibrio tra le due conformazioni s-cis ed s-trans, e le loro distribuzioni influenzano il meccanismo della reazione. Generalmente, sotto fotolisi, i composti nella conformazione s -cis reagiscono in modo concertato a causa della relazione antiperiplanare tra i gruppi uscenti e migranti, mentre i composti nella conformazione s -trans reagiscono gradatamente attraverso un intermedio carbene o non lo fanno riarrangiare. (2) indipendentemente dal meccanismo di reazione, il riarrangiamento produce un intermedio chetene, che può essere intrappolato da un nucleofilo debolmente acido, come un alcool o un'ammina, producendo il corrispondente estere o ammide, o un olefine, per dare un addotto [2+2] cicloaddizione. Gli acidi forti non si riarrangiano, piuttosto protonano l'α-carbonio e danno i prodotti di una reazione SN2.

 
Meccanismo concertato e graduale per conformeri nello stato fondamentale.

Stereochimica di chetoni α-diazo

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Conoscere la stereochimica di un chetone α-diazo è essenziale per chiarire il meccanismo del riarrangiamento. I composti α-diazocarbonili solitamente sono planari localmente, con grandi barriere rotazionali (55–65 kJ/mol) dovuto al carattere olefine C-C tra il carbonile e l'α-carbonio, illustrato in basso nella struttura di risonanza più a destra.[4] Una barriera così grande rallenta le rotazioni molecolari sufficientemente per portare a un equilibrio tra i due conformeri s-trans ed s-cis. I conformeri s-cis sono elettronicamente favoriti perchè vi è attrazione coulombiana tra l'ossigeno con carica negativa parziale e il catione azoto, come illustrato in basso nella struttura di risonanza più a destra.[2] Se R1 è grande ed R2 è H, s-cis è stericamente favorito. Se R1 ed R2 sono grandi, s-trans è stericamente favorito; se ambedue i sostituenti sono motlo grandi, la repulsione sterica può superare l'attrazione coulombiana, portando a una preferenza per l's-trans. I substrati ciclici piccoli e medi sono vincolati nella conformazione s -cis.

 
Equilibrio tra s-trans e s-cis con struttura di risonanza che mostra il carattere olefinico del legame C-C, e l'attrazione Coulombiana nel s-cis.

Meccanismo concertato

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When the α-diazo ketone is in the s-cis conformation, the leaving group (N2) and the migrating group (R1) are antiperiplanar, which favors a concerted mechanism, in which nitrogen extrusion occurs concurrently with 1,2-alkyl shift. There is evidence this mechanism occurs in both thermolytic and photolytic methods, when the s-cis-conformer is strongly favored.[5][6]

 
Meccanismo concertato del confomero s-cis.

CIDNP studies show that photochemical rearrangement of diazoacetone, which largely exists in the s-cis-conformer, is concerted.[7] Product ratios from direct and triplet-sensitized photolysis have been used as evidence for proposals that claim that concerted products arise from the s-cis-conformer and stepwise products occur through the s-trans-conformer.[8]

Meccanismo graduale

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s-trans-α-Diazo ketones do not have an antiperiplanar relationship between the leaving and migrating group, and thus are thought to generally rearrange stepwise. The stepwise mechanism begins with nitrogen extrusion, forming an α-ketocarbene. The α-ketocarbene can either undergo a 1,2-alkyl shift, to give the ketene product, or can undergo a 4π electrocyclic ring closure, to form an antiaromatic oxirene. This oxirene can reopen in two ways, to either α-ketocarbene, which can then form the ketene product.

 
Meccanismo graduale del coformero s-trans con estrusione sequenziale di azoto per dare il chetocarbene, che può o subire uno spostamento 1,2-alchile per formare il carbene o subire la chiusura dell'anello 4π elettrociclico per formare l'intermedio ossireno.

There are two primary arguments for stepwise mechanisms. The first is that rate constants of Wolff rearrangements depend on the stability of the formed carbene, rather than the migratory aptitude of the migrating group.[9] The most definitive evidence is isotopic scrambling of the ketene, as predicted by an oxirene intermediate, which can only occur in the stepwise path. In the scheme below, the red carbon is 13C labelled. The symmetric oxirene intermediate can open either way, scrambling the 13C label. If the substituents R1 and R2 are the same, one can quantify the ratio of products stemming from the concerted and stepwise mechanisms; if the substituents are different, the oxirene will have a preference in the direction it opens, and a ratio cannot be quantified, but any scrambling indicates some reactant is going through a stepwise mechanism.[2] In photolysis of diazo acetaldehyde, 8% of the label is scrambled, indicating that 16% of product is formed via the oxirene intermediate.[10] Under photolysis, the biphenyl (R1=R2=phenyl) substrate shows 20–30% label migration, implying 40–60% of product goes through the oxirene intermediate.[11] α-diazocyclohexanone shows no label scrambling under photolytic conditions, as it is entirely s-cis, and thus all substrate goes through the concerted mechanism, avoiding the oxirene intermediate.[12]

 
Rimescolamento isotopico del chetocarbene marcato 13C tramite ossireno simmetrico.

Isotopic labeling studies have been used extensively to measure the ratio of product stemming from a concerted mechanism versus a stepwise mechanism.[13] These studies confirm that reactants that prefer s-trans conformations tend to undergo stepwise reaction. The degree of scrambling is also affected by carbene stability, migratory abilities, and nucleophilicity of solvent. The observation that the migratory ability of a substituent is inversely proportional to amount of carbene formed, indicates that under photolysis, there are competing pathways for many Wolff reactions.[13] The only Wolff rearrangements that show no scrambling are s-cis constrained cyclic α-diazo ketones. [12]

Conclusione sul meccanismo

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Under both thermolytic and photolytic conditions, there exist competing concerted and stepwise mechanisms. Many mechanistic studies have been carried out, including conformational, sensitization, kinetic, and isotopic scrambling studies. These all point to competing mechanisms, with general trends. α-Diazo ketones that exist in the s-cis conformation generally undergo a concerted mechanism, whereas those in the s-trans conformation undergo a stepwise mechanism.[2] α-diazo ketones with better migratory groups prefer a concerted mechanism.[2] However, for all substrates except cyclic α-diazo ketones that exist solely in the s-cis conformation, products come from a combination of both pathways.[2] Transition metal mediated reactions are quite varied; however, they generally prefer forming the metal carbene intermediate.[3] The complete mechanism under photolysis can be approximated in the following figure:

 
Illustrazione del meccanismo di riarrangiamento, in alto il meccanismo concertato e in basso il meccanismo graduale con gli intermedi carbene e ossireno.

Tendenze migratorie

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The mechanism of the Wolff rearrangement is dependent on the aptitude of the migratory group. Migratory abilities have been determined by competition studies. In general, hydrogen migrates the fastest, and alkyl and aryl groups migrate at approximately the same rate, with alkyl migrations favored under photolysis, and aryl migrations preferred under thermolysis.[14] Substituent effects on aryl groups are negligible, with the exception of NO2, which is a poor migrator.[14] In competition studies, electron deficient alkyl, aryl, and carbonyl groups cannot compete with other migrating groups, but are still competent.[15][16][17] Heteroatoms, in general, are poor migratory groups, because their ability to donate electron density from their p orbitals into the π* C=O bond decreases migratory ability.[2] The trend is as follows: [2]

Photochemical reactions: H > alkyl ≥ aryl >> SR > OR ≥ NR2

Thermal reactions H > aryl ≥ alkyl (heteroatoms do not migrate)

Preparazione dei composti α-diazocarbonili

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While known since 1902, the Wolff rearrangement did not become synthetically useful until the early 1930s, when efficient methods became available to synthesize α-diazocarbonyl compounds. The primary ways to prepare these substrates today are via the Arndt-Eistert procedure, the Franzen modification to the Dakin-West reaction , and diazo-transfer methods.

Procedura di Arndt-Eistert

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The Arndt–Eistert reaction[18] involves the acylation of diazomethane with an acid chloride, to yield a primary α-diazo ketone. The carbon terminus of diazomethane adds to the carbonyl, to create a tetrahedral intermediate, which eliminates chloride. The chloride then deprotonates the intermediate to give the α-diazo ketone product.

 
1 - procedura di Arndt-Eistert

These α-diazo ketones are unstable under acidic conditions, as the α-carbon can be protonated by HCl and SN2 displacement of nitrogen can occur by chloride.

 
2 - procedura di Arndt-Eistert

Thus, triethylamine or a second equivalent of diazomethane must be added to scavenge the HCl produced in order to prevent decomposition.[19]

 
3 - procedura di Arndt-Eistert

This reaction is occasionally done with acid anhydrides, which yields a one-to-one mixture of α-diazo ketone and the corresponding methyl ester.[20] This method can also be used with primary diazoalkanes, to produce secondary α-diazo ketones. However, there are many limitations. Primary diazoalkanes undergo azo coupling to form azines; thus the reaction conditions must be altered such that acid chloride is added to a solution of diazoalkane and triethylamine at low temperature.[21][22] In addition, primary diazoalkanes are very reactive, incompatible with acidic functionalities, and will react with activated alkenes including unsaturated carbonyls to give 1,3-dipolar cycloaddition products.

Modifica di Franzen alla reazione del Dakin-Ovest

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The Dakin–West reaction is a reaction of an amino acid with an acid anhydride in the presence of a base to form keto-amides. The Franzen modification[21] to the Dakin–West reaction[23] is a more effective way to make secondary α-diazo ketones. The Franzen modification nitrosates the keto-amide with N2O3 in acetic acid, and the resulting product reacts with methoxide in methanol to give the secondary α-diazo ketone.

 
Modifica di Franzen alla reazione del Dakin-Ovest

Reazioni di diazo-trasferimento

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Diazo-transfer reactions are commonly used methods, in which an organic azide, usually tosylazide, and an activated methylene (i.e. a methylene with two withdrawing groups) react in the presence of a base to give an α-diazo-1,3-diketone.[24] The base deprotonates the methylene, yielding an enolate, which reacts with tosylazide and subsequently decomposes in the presence of a weak acid, to give the α-diazo-1,3-diketone.

 
diazo-trasferimento

The necessary requirement of two electron withdrawing groups makes this reaction one of limited scope. The scope can be broadened to substrates containing one electron withdrawing group by formylating a ketone via a Claisen condensation, followed by diazo-transfer and deformylative group transfer.[25]

 
diazo-trasferimento formilativo

One of the greatest advantages of this method is its compatibility with unsaturated ketones. However, to achieve kinetic regioselectivity in enolate formation and greater compatibility with unsaturated carbonyls, one can induce enolate formation with lithium hexamethyldisilazideand subsequently trifluoroacylate rather than formylate.[26]

 
diazo-trasferimento di Danheiser

Voci correlate

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Note

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  1. ^ Meier, H.; Zeller, K.-P (1975), "The Wolff Rearrangement of α-Diazo Carbonyl Compounds", Angew. Chem. Int. Ed. Engl. 14(1): 32–43, DOI: 10.1002/anie.197500321
  2. ^ a b c d e f g h Kirmse, W (2002), "100 Years of the Wolff Rearrangement", Eur. J. Org. Chem. 2002 (14): 2193–2256, DOI: 10.1002/1099-0690(200207)2002:14<2193::AID-EJOC2193>3.0.CO;2-D
  3. ^ a b Gill, G. B. (1991) “The Wolff Rearrangement.” in Trost, B. M. Flemming, I. (eds.) Comp. Org. Synth. Oxford: Pergamon. 3:887. DOI: 10.1016/B978-0-08-052349-1.00085-8. ISBN 978-0-08-052349-1
  4. ^ (EN) Pecile, C. Foffani, F. Chersetti, S., The interaction of diazocarbonyl compounds with hydroxylic solvents, in Tetrahedron, vol. 20, n. 4, 1964, pp. 823, DOI:10.1016/S0040-4020(01)98414-5.
  5. ^ Kaplan, F. Meloy, G. K., The Structure of Diazoketones. A Study of Hindered Internal Rotation1,2, in J. Am. Chem. Soc., vol. 88, n. 5, 1966, p. 950, DOI:10.1021/ja00957a017.
  6. ^ (EN) Kaplan, F. Meloy, G. K., The Structure of Diazoketones. A Study of Hindered Internal Rotation1,2, in J. Am. Chem. Soc., vol. 88, n. 5, 1966, pp. 950, DOI:10.1021/ja00957a017.
  7. ^ Roth, H. D. Manion, M.L., Solution photochemistry of diazoacetone. Wolff rearrangement and acetylmethylene, in J. Am. Chem. Soc., vol. 98, n. 11, 1976, p. 3392, DOI:10.1021/ja00427a067.
  8. ^ Tomioka, H. Okuno, H. Kondo, S. Izawa, Y., Direct evidence for ketocarbene-ketocarbene interconversion, in J. Am. Chem. Soc., vol. 102, n. 23, 1980, p. 7123, DOI:10.1021/ja00543a050.
  9. ^ Regitz, M. W, Bartz., Untersuchungen an Diazoverbindungen, VII. Vergleichende kinetische Untersuchungen zur thermischen Stabilität aliphatischer Diazoverbindungen, in Chem. Ber., vol. 103, n. 5, 1970, p. 1477, DOI:10.1002/cber.19701030519.
  10. ^ Zeller, K. P., Zur formylcarben-oxiren-isomerisierung, in Tetrahedron Letters, vol. 18, n. 8, 1977, p. 707, DOI:10.1016/S0040-4039(01)92732-7.
  11. ^ Zeller, K. P. Meier, H. Kolshorn, H. Mueller, E., Zum Mechanismus der Wolff-Umlagerung, in Chem. Ber., vol. 105, n. 6, 1972, p. 1875, DOI:10.1002/cber.19721050610.
  12. ^ a b Timm, U. Zeller, K. P. Meier, H., Photolyse von 2-oxo-[2-13c]-1-diazocyclohexan. Ein beitrag zum oxiren-problem, in Tetrahedron, vol. 33, n. 4, 1977, p. 453, DOI:10.1016/0040-4020(77)80104-X.
  13. ^ a b Fenwick, J. Frater, G. Ogi, K. Strausz, O.P., Mechanism of the Wolff rearrangement. IV. Role of oxirene in the photolysis of .alpha.-diazo ketones and ketenes, in J. Am. Chem. Soc., vol. 95, 1973, p. 124, DOI:10.1021/ja00782a021.
  14. ^ a b Zeller, K. P. Meier, H. Müller, E., Untersuchungen zur Wolff-Umlagerung—II, in Tetrahedron, vol. 28, n. 23, 1972, p. 5831, DOI:10.1016/S0040-4020(01)88926-2.
  15. ^ Wilds, A. L. Meader, A. L., The use of higher diazohydrocarbons in the Arndt-Eistert synthesis, in J. Org. Chem., vol. 13, n. 5, 1948, pp. 763–79, DOI:10.1021/jo01163a024.
  16. ^ Gallucci, R. R. Jones, M. Jr., Photolysis of methyl 3-diazo-2-oxopropionate. Wolff migration of the carbomethoxy group, in J. Org. Chem., vol. 50, n. 22, 1985, p. 4404, DOI:10.1021/jo00222a047.
  17. ^ Weygand, F. Dworschak, H. Koch, K. Konstas, S., Reaktionen des Trifluoracetyl-carbäthoxy-carbens II. Mitteilung, in Angew. Chem., vol. 73, n. 11, 1961, p. 409, DOI:10.1002/ange.19610731116.
  18. ^ Arndt, F. Eistert, B. Partale, W., Diazo-methan undo-Nitroverbindungen, II.:N-Oxy-isatin auso-Nitro-benzoylchlorid, in Chem. Ber., vol. 60, n. 6, 1927, p. 1364, DOI:10.1002/cber.19270600616.
  19. ^ Clibbens, D. A. Nierenstein, M., CLXV.—The action of diazomethane on some aromatic acyl chlorides, in J. Chem. Soc., vol. 107, 1915, p. 1491, DOI:10.1039/ct9150701491.
  20. ^ Bradley, W. Robinson, R., The Action of Diazomethane on Benzoic and Succinic Anhydrides, and a Reply to Malkin and Nierenstein, in J. Am. Chem. Soc., vol. 52, n. 4, 1930, p. 1558, DOI:10.1021/ja01367a040.
  21. ^ a b Franzen, V., Eine neue Methode zur Darstellung α,β-ungesättiger Ketone. Zerfall der Diazoketone R—CO—CN2—CH2—R′, in Justus Liebigs Annalen der Chemie, vol. 602, 1957, p. 199, DOI:10.1002/jlac.19576020116.
  22. ^ Yates, P. Farnum, D. G. Wiley, D. W., Chem. Ind., 1958, p. 69.
  23. ^ Dakin, H. D. West, R., A General Reaction of Amino Acids, in J. Biol. Chem., vol. 78, 1928, p. 91.
  24. ^ Regitz, M. Liedhegener, A., Reaktionen aktiver Methylenverbindungen mit Aziden, XII. Synthese von Diacyl-diazomethanen durch Diazogruppen-Übertragung, in Chem. Ber., vol. 99, n. 10, 1966, p. 3128, DOI:10.1002/cber.19660991010.
  25. ^ Regitz, M. Rüter,, Reaktionen CH-aktiver Verbindungen mit Aziden, XVIII. Synthese von 2-Oxo-1-diazo-cycloalkanen durch entformylierende Diazogruppen-Übertragung, in J. Chem. Ber., vol. 101, n. 4, 1968, p. 1263, DOI:10.1002/cber.19681010419.
  26. ^ Danheiser, R. L. Miller, R. F. Brisbois, R. G. Park, S. Z., An improved method for the synthesis of .alpha.-diazo ketones, in J Org Chem, vol. 55, n. 6, 1990, p. 1959, DOI:10.1021/jo00293a053.

Altri progetti

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  Portale Chimica: il portale della scienza della composizione, delle proprietà e delle trasformazioni della materia
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