The document summarizes the Wolff rearrangement reaction, which was discovered by German chemist Ludwig Wolff in 1902. The Wolff rearrangement involves the conversion of an α-diazocarbonyl compound into a ketene through loss of dinitrogen with an accompanying 1,2-rearrangement. This yields a ketene intermediate that can undergo nucleophilic attack or [2+2] cycloaddition reactions. The reaction proceeds through either a concerted or stepwise carbene-mediated mechanism. The Wolff rearrangement has synthetic utility but also limitations due to the reactivity of α-diazocarbonyl compounds.

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

7. 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.

8. 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.

9. 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);

10. 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

24. 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.