Wolff rearrangement

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 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 reactions.In 1902, Wolff discovered that treating diazoacetophenone with silver (I) oxide and water resulted in formation of phenylacetic acid. Similarly, treatment with silver (I) oxide and ammonia formed phenylacetamide. A few years later, in an independent study, Schröter observed similar results. The reaction is occasionally called the Wolff-Schröter rearrangement. The Wolff rearrangement was not commonly used until 20 years after it was discovered, as facile diazo ketone synthesis was unknown until the 1930s. The reaction has proven useful in synthetic organic chemistry and many reviews have been published.The mechanistic pathway of the Wolff-rearrangement has been the subject of much debate, as there are often competing concerted and stepwise mechanisms. However, two aspects of the mechanism can be agreed upon. First, α-diazocarbonyl compounds are in an equilibrium of s-cis and s-trans-conformers, the distribution of which may influence the mechanism of the reaction. Generally, under photolysis, compounds in the s-cis conformation react in a concerted manner due to the antiperiplanar relationship between the leaving and migrating groups, whereas compounds in the s-trans conformation react stepwise through a carbene intermediate or do not rearrange. Second, regardless of the reaction mechanism, the rearrangement gives a ketene intermediate, which can be trapped by a weakly acidic nucleophile, such as an alcohol or amine, to give the corresponding ester or amide, or an olefin, to give a cycloaddition adduct. Strong acids do not rearrange, but rather protonate the α-carbon and give SN2 products. 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.Wolff rearrangements can be induced under thermolytic, photolytic, and transition-metal-catalyzed conditions.The Wolff rearrangement has a few retrons, depending on the reaction out of the ketene intermediate. A carboxylic acid derivative with an α-methylene group is a retron for an Arndt-Eistert type homologation. An acid in which the α-carbon belongs to a ring is a retron for a Wolff rearrangement ring contraction.