Wolff rearrangement synthesis

Williamson synthesis Wohl-Ziegler reaction Wolff rearrangement Wolff Kishner reduction Wurtz reaction Wurtz-Fittig reaction... 

Wolff rearrangement, 7, 193 pyrylium salt synthesis from, 3, 871... 

Photochemical Wolff rearrangement of 2-diazo-3-ketones, though not widely used as a source of A-norsteroids, is discussed in section V in connection with the mechanism of the important photochemical synthesis of D-norsteroids. Photochemical rearrangement of epoxy ketones is a source of A-nosteroids these rearrangements are discussed in chapter 13. Other photochemical routes to A-norsteroids are known." " ... 

Scheme 10.14 gives some other examples of Wolff rearrangement reactions. Entries 1 and 2 are reactions carried out under the classical silver ion catalysis conditions. Entry 3 is an example of a thermolysis. Entries 4 to 7 are ring contractions done under photolytic conditions. Entry 8, done using a silver catalyst, was a step in the synthesis of macbecin, an antitumor antibiotic. Entry 9, a step in the synthesis of a drug candidate, illustrates direct formation of an amide by trapping the ketene intermediate with an amine. 

Apart from the widely studied silver(i) A-heterocyclic carbenes, Stoltz and Beauchamp made the first report on the gas-phase synthesis of silver(i) Fischer carbenes from the loss of N2 in various diazo malonates upon electrospray ionization and subsequent collisional activation.118 The carbenes generated were capable of undergoing multiple Wolff rearrangements and loss of CO (Scheme 18). 

A similar synthesis of mechanistic interest rather than preparative value involves the thermal reaction of dimethyl 2,5-bisdiazo-3,4-diketoadipate (89, Scheme 23) with benzofuran (91)." The presumed intermediate is the pyrone cation 90 produced from the adipate 89 by the Wolff rearrangement, cyclization, and loss of nitrogen. Electrophilic substitution then affords the benzofuran 92, which can be isolated. Ring opening and cyclization of the resultant ketene 93 then affords the dibenzofuran 94 in poor (0.4%) yield. 

Other synthetic routes to the carbapenem ring system include photolytic Wolff rearrangement (73JCS(P 1)2024), aldol condensation (78JA313), addition-cyclization (80JOC1135) and /3-lactam formation (78JOC4438,79TL4359). An excellent review of carbapenem synthesis has recently appeared (82H(17)463). 

Most important, from a preparative point of view, for the synthesis of four-membered rings are the Wolff rearrangement of mono- or polycyclic x-diazocyclopentanones, the Favorskii rearrangement of polycyclic x-halocyclopentanones and, to a lesser extent, various rearrangements including cationic intermediates. 

The Wolff rearrangement has been very successfully used in the synthesis of propellanes.40 The highly strained 3-diazo[3,2.2]propellan-2-one was photolyzed in dichloromethane at — 70 °C in the presence of dimethylamine to give A W-dimethyl tricyclo[2.2.2.0 u4]octane-2-carboxamide (5), a very highly strained interesting compound with inverted geometry at the bridgehead carbons,42 in 40% yield.41... 

WOLFF REARRANGEMENT. Rearrangement of diazoketone to ketenes by action of heat, light or some metallic catalyst. The rearrangement is the key step in the Arndt-F.istert synthesis. 

Widman-Stoermer synthesis, 3, 43 Wild-fire toxin, 7, 249 Willardiine, synthesis, 3, 146 Willgerodt reaction thiophene synthesis by, 4, 883 Williamson reaction oxetane synthesis by, 7, 390-391 Withasomnine occurrence, 5, 302 Wittig reaction crown ethers and, 7, 759 Wittig-Homer reactions crown ethers and, 7, 759 Wolff rearrangement oxirenes in, 7, 120, 126... 

The Arndt-Eistert Synthesis allows the formation of homologated carboxylic acids or their derivatives by reaction of the activated carboxylic acids with diazomethane and subsequent Wolff-Rearrangement of the intermediate diazoketones in the presence of nucleophiles such as water, alcohols, or amines. 

The Wolff rearrangement and the Arndt-Eistert homologation sequence are very useful in organic synthesis. One of the most popular applications involves amino acids. An interesting example has been described as a key reaction in the synthesis of a 14C-labeled amino acid used for deciphering the biosynthesis of penicillin N from glutamic acid (Scheme 3.2).9 This rearrangement proceeds without racemization and can thus be applied in peptide synthesis. 

Since ketene is probably the intermediate of the Wolff rearrangement, the choice of solvents dictates the nature of the product. Indeed, water gave carboxylic acids, whereas alcohols or amines led to esters and amides, respectively. These combinations have been applied to the synthesis of more complex molecules. For example, the total synthesis of carbonolide B, a 16-membered macrolide antibiotic, relied on Amdt-Eistert homologation. In this sequence, a protected furanuronic acid was transformed to the corresponding a-diazoketone, which was then converted to its homologous carboxylic ester. The reaction was achieved using catalytic amounts of silver benzoate and excess of triethylamine in methanol (Scheme 3.4).11... 

Of course, one can also carry out Wolff rearrangements in the presence of nucleophiles other than H20. Ketenes are then produced in their presence, and the addition products of these nucleophiles are therefore isolated. Figure 14.28 shows how one can add an alcohol to a ketene in this way. An alcohol addition to a ketene is also involved in the /3-ketoester synthesis discussed in Side Note 6.2. 

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