Wolff

rearrangement

1. BY Dr . G.C.Wadhawa DEPARTMENT OF CHEMISTRY K. B. P . College,Vashi,Navimumbai Wolff Rearrangement Reaction

2. Ludwig Wolff  (27 September 1857 – 24 February 1919), born in Neustadt in Palatinate, was a German chemist . He studied chemistry at the University of Strasbourg, where he received his Ph.D. from Rudolph Fittig in 1882. He became Professor of analytical chemistry at the University of Jena in 1891 and held this position till his death in 1919. In 1911 he published a new reaction now known as the Wolff- Kishner reduction. His name is also associated with the chemical reaction known as the Wolff rearrangement

3. The  Wolff rearrangement  is a reaction in organic chemistry in which an α- diazocarbonyl compound is converted into a ketene by loss of dinitrogen with accompanying 1,2-rearrangement. The Wolff rearrangement yields a ketene as an intermediate product, which can undergo nucleophilic attack with weakly acidic nucleophiles such as water, alcohols, and amines, to generate carboxylic acid derivatives or undergo [2+2] cycloaddition reactions to form four- membered rings. The mechanism of the Wolff rearrangement has been the subject of debate since its first use. No single mechanism sufficiently describes the reaction, and there are often competing concerted and carbene-mediated pathways; for simplicity, only the textbook, concerted mechanism is shown below. The reaction was discovered by Ludwig Wolff in 1902 .   The Wolff rearrangement has great synthetic utility due to the accessibility of α- diazocarbonyl compounds, variety of reactions from the ketene intermediate, and stereochemical  retention of the migrating group .  However, the Wolff rearrangement has limitations due to the highly reactive nature of α- diazocarbonyl compounds, which can undergo a variety of competing reaction

4. α- Diazoketones undergo the Wolff Rearrangement thermally in the range between room temperature and 750 °C in gas phase pyrolysis . Due to competing reactions at elevated temperatures, the photochemical and metal-catalyzed variants that feature a significantly lowered reaction temperature are often preferred (Zeller,  Angew . Chem. Int. Ed. ,  1975 ,  14 , 32. DOI). Nitrogen extrusion and the 1,2-shift can occur either in a concerted manner or stepwise via a carbene intermediate: Silver ion catalysis fails with sterically hindered substrates, pointing to the requisite formation of a substrate complex with the ion. In these cases, photochemical excitation is the method of choice.

5. The solvent can affect the course of the reaction. If Wolff-Rearrangements are conducted in MeOH as solvent, the occurrence of side products derived from an O-H insertion point to the intermediacy of carbenes The course of the reaction and the migratory preferences can depend on the conditions (thermal, photochemical, metal ion catalysis) of the reaction. Analysis of the product distribution helps to determine different degrees of concertedness or the migratory aptitude of the group that rearranges. If R is phenyl, the main product comes from the rearrangement, whereas the methyl group gives more of the insertion side product.

6. 1) reaction of an acyl halide or anhydride with two equivalents of diazomethane in ether or DCM solution at room temperature or below (Arndt- Eistert homologation);however, only one equivalent is needed of higher diazoalkanes , and low temperatures are necessary due to competing azo coupling; 2) sequential treatment of N- acyl -α-amino ketones (prepared by the Dakin-West reaction) with N2O3 and sodium methoxide in methanol affords secondary α- diazo ketones , so the cumbersome use of higher diazoalkanes is avoided; 3) transfer of the diazo group from an organic azide (e.g., tosyl azide ) to a substrate containing an active methylene group (e.g., β- keto ester or β- keto nitrile ) in the presence of a base ( Regitz diazo transfer); 4) simple diazo monoketones are synthesized from ketones by the introduction of a formyl group at the α-position via a Claisen reaction and then treatment of theresulting α- formyl derivative with tosyl azide and a tertiary amine ( deformylative diazo -transfer); 5) oxidation of α- ketoximes with chloramine ; hydroxide ion assisted decomposition of tosylhydrazones . The general featuresof the Wolff rearrangement are: 1) the reaction can be initiated thermally, photolytically , or by transition metal catalysis; 2) thermal conditions are not used frequently, since delicate substrates may degrade and side reactions arefrequent (e.g., direct displacement of the diazo group without rearrangement);

7. 6) the use of transition metal complexes does not only reduce the required reaction temperature considerably compared to the thermal process, but also changes the reactivity of the α- keto carbene intermediate by the formation of less reactive metal carbene complexes ( Rh - and Pd-complexes usually prevent the Wolff rearrangement from taking place); 7) freshly prepared silver(I)oxide or silver(I)benzoate are best suited for the reaction; 8) photochemical activation is convenient, and it takes place even at low temperatures, but it can be problematic if the product is photolabile ; 9) if the migrating group has a stereocenter , the stereochemistry remains unchanged (net retention of configuration) after the migration; 10) theketene products are electrophilic and can react with various nucleophiles as well as undergo [2+2] cycloaddition reactions with alkenes; 11) cyclic diazo ketones undergo ring-contraction, and the process is well-suited for the preparation of strained ring systems; 12) α,β -unsaturated diazo ketones undergo the vinylogous Wolff rearrangementto give skeletally rearranged γ,δ -unsaturated esters (alternative to Claisen -type rearrangements);1and 13) since α- diazo ketones are very reactive compounds, numerous side reactions are possible that can be avoided or minimized by the careful choice of reaction conditions.9

8. References 1. Wolff, L. Ann. 1912, 394, 23-108. Johann Ludwig Wolff (1857-1919) earned his doctorate in 1882 under Fittig at Strasbourg, where he later became an instructor. In 1891, Wolff joined the faculty of Jena, where he collaborated with Knorr for 27 years. 2. Zeller, K.-P.; Meier, H.; Müller, E. Tetrahedron 1972, 28, 5831-5838. 3. Kappe, C.; Fäber, G.; Wentrup, C.; Kappe, T. Ber. 1993, 126, 235-2360. 4. Taber, D. F.; Kong, S.; Malcolm, S. C. J. Org. Chem. 1998, 63, 795-7956. 5. Yang, H.; Foster, K.; Stephenson, C. R. J.; Brown, W.; Roberts, E. Org. Lett . 2000, 2, 217-2179. 6. Kirmse , W. “100 years of the Wolff Rearrangement” Eur. J. Org. Chem. 2002, 219-2256. (Review). 7. Julian, R. R.; May, J. A.; Stoltz , B. M.; Beauchamp, J. L. J. Am. Chem. Soc. 2003, 125, 447-4486. 8. Zeller, K.-P.; Blocher , A.; Haiss , P. Mini-Reviews Org. Chem. 2004, 1, 29-308. (Review). 9. Davies, J. R.; Kane, P. D.; Moody, C. J.; Slawin , A. M. Z. J. Org. Chem. 2005, 70, 584-5851. 10. Kumar, R. R.; Balasubramanian , M. Wolff Rearrangement. In Name Reactions for Homologations-Part II; Li, J. J., Ed.; Wiley: Hoboken, NJ, 2009, pp 25-273. (Review). 11. Somai Magar, K. B.; Lee, Y. R. Org. Lett. 2013, 15, 428-4291.