Wolff rearrangements

The stereoselective total synthesis of tt)-campherenone was accomplished by T. Uyehara and co-workers based on a photochemical Wolff rearrangement. The bicyclic ketone was treated with 2,4,6-triisopropylbenzenesulfonyl azide (trisyl azide) under homogeneous basic conditions and the a-diazo ketone was obtained in excellent yield. The photochemical rearrangement of the diazo ketone was conducted in a THF-water mixture using a high-pressure 100 W mercury lamp. The ring-contracted acid was isolated as a 4 1 mixture of endo and exo products. 

In the laboratory of K. Fukumoto, the stereoselective total synthesis of (+)-A -capnellene was carried out using an intramolecular Diels-Alder reaction to obtain a tricyclic 5-5-6 system. Since the target molecule was a triquinane, the six-membered ring had to be converted to a five-membered one, a transformation achieved by a Wolff rearrangement. The required a-diazo ketone was prepared via a deformylative diazo transfer reaction and was photolyzed in methanol. The ring-contracted methyl ester was isolated as a 3 1 mixture of separable isomers favoring the a-isomer. 

The natural product (-)-oxetanocin is an unprecedented oxetanosyl-A/-glycoside that inhibits the in vitro replication of human immunodeficiency virus (HIV). In order to prepare multigram quantities of the compound, D.W. Norbeck et al. devised a short and efficient synthetic strategy. The cornerstone of the strategy was the Wolff rearrangement of a five-membered diazo ketone. The diazo transfer was achieved by first converting the ketone to an enamino ketone followed by treatment with triflyl azide. Upon irradiation with a 450 W Pyrex filtered Hanovia lamp, the isomeric oxetanes (a 3 = 2 1) were obtained in 36% yield. 

Danheiser and co-workers generated a key vinylketene intermediate via tandem Wolff rearrangement-ketene-alkyne cycloaddition to utilize it in a photochemical aromatic annulation reaction Danheiser benzannulation) for the total synthesis of the phenalenone diterpene salvilenone.  

Ziegler, A. Spath, E. Schaaf, W. Schumann, E. Winkelmann, Justus Liebigs Ann. Chem. 1942, 55/, 80-119. 

An a-diazo ketone 1 can decompose to give a ketocarbene, which further reacts by migration of a group R to yield a ketene 2. Reaction of ketene 2 with water results in formation of a carboxylic acid 3. The Woljf re arrangement is one step of the Arndt-Eistert reaction. Decomposition of diazo ketone 1 can be accomplished thermally, photochemically or catalytically as catalyst amorphous silver oxide is commonly used  

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7  

The intermediacy of a ketocarbene species 4 is generally accepted for the thermal or photochemical Wolff rearrangement oxirenes 8 that are in equilibrium with ketocarbenes, have been identified as intermediates  

With cyclic a-diazo ketones, e.g. a-diazo cyclohexanone 9, the rearrangement results in a ring contraction by one carbon  

Treatment of the ketene with water would give the corresponding homologated carboxylic acid. 

Justus Liebigs Ann. Chem. 1912, 394, 25. Johann Ludwig Wolff (1857-1919) obtained 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. 

Zeller, K.-P. Blocher, A. Haiss, P. Oxirene participation in the Photochemical Wolff Rearrangement Mlnl-Revlewx in Organic Chemistry 2004,1, 291-308. (Review). 

Methylene ( CH2) is of higher energy content than CCl2, and is more reactive and less selective. Its reactivity is illustrated by its reactions with cyclohexene, which include both addition to the double bond and insertion in the saturated and 

Different carbenes exhibit different selectivities toward insertion and cycloaddi-hon reactions. However, the reaction of cyclohexene with dichlorocarbene resulted in a 60/6 isolated yield of the dichloro derivative of norcarane, that is, 7,7- 

Singlet carbenes will rearrange to isoelectronic structures in which all atoms have an octet of electrons if hydrogen atoms are located on adjacent carbon atoms. 

If intramolecular reactions cannot occur, the carbanion-carbocation character of a singlet carbene can lead to reactions that occur through ionic species. Singlet carbenes react with methanol by nucleophilic abstraction of a proton, resulting in a carbocation, which subsequently reacts with the alcohol to produce an ether. For 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 273, Springer-Verlag Berlin Heidelberg 2009 

Balasubramanian, M. Wolff Rearrangement. In Name Reactions for Homologations-Part 11 Li, J. J., Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2009, pp ISl-TTi. (Review). 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications DOI 10.1007/978-3-319-03979-4 292, Springer International Publishing Switzerland 2014 

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

The reaction of cyclohexene with the diazopyruvate 25 gives unexpectedly ethyl 3-cyclohexenyl malonate (26), involving Wolff rearrangement. No cyclo-propanation takes place[28]. 1,3-Dipolar cycloaddition takes place by the reaction of acrylonitrile with diazoacetate to afford the oxazole derivative 27[29]. Bis(trimethylstannyl)diazomethane (28) undergoes Pd(0)-catalyzed rearrangement to give the A -stannylcarbodiimide 29 under mild conditions[30]. 

Thiazole acid chlorides react with diazomethane to give the diazoketone. The later reacts with alcoholic hydrogen chloride to give chloroacetylthiazole (Scheme 16). However, the Wolff rearrangement of the diazoketone is not consistently satisfactory (82). Heated with alcohol in the presence of copper oxide the 5-diazomethylketone (24) gives ethyl 5-thiazoleacetate (25) instead of the expected ethoxymethyl 5-thiazolyl ketone (Scheme 17) (83). 

Several ring contraction routes to /3-lactams have been developed. One of the most important is the photochemical Wolff rearrangement of 3-diazopyrrolidine-2,4-diones (178), which provides a general route to 3-carboxyazetidin-2-ones (179). Lack of stereoselectivity is a problem, but facile epimerization is possible because of the electron withdrawing 3-substituent (78T1731). 

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

D. Cyclic a-Diazoketones Ring-Contraction in Photolytic Wolff Rearrangements... 

The photolytic decomposition of a-diazoketones, accompanied by rearrangement to ketene (photolytic Wolff rearrangement), has been used successfully in the preparation of A-nor- and C-norsteroids. The method is reviewed in chapter 15 by R. M. Scribner. ... 

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." " ... 

The diazo ketone 3, when treated with silver oxide as catalyst, decomposes into ketocarbene 5 and dinitrogen Na. This decomposition reaction can also be achieved by heating or by irradiation with uv-light. The ketocarbene undergoes a Wolff rearrangement to give a ketene 6 ... 

The Wolff rearrangement is a versatile reaction R can be alkyl as well as aryl most functional groups do not interfere. The generally mild reaction conditions permit an application to sensitive substrates. 

In this section we first discuss photolytic reactions of arenediazonium salts and report on quinone diazides at the end of the section in the context of imaging technology. Diazoalkenes, non-quinonoid diazo ketones, and the Wolff rearrangement are treated in the book on aliphatic diazo compounds (Zollinger, 1995, Chap. 8). 

The photolysis of o-quinone diazides was carefully investigated by Stis in 1944, many years before the development of photoresists. Scheme 10-102 shows the photolysis sequence for the diazoquinone 10.75 formed in the diazotization of 2-amino-1-naphthol. The product of the photolytic step is a ketocarbene (10.76), which undergoes a Wolff rearrangement to a ketene (10.77). In the presence of water in-dene-3-carboxylic acid (10.78) is formed this compound is highly soluble in water and can be removed in the development step. The mechanism given in Scheme 10-102 was not postulated as such by Stis, because in 1944 ketocarbenes were unknown (for a mechanistic discussion of such Wolff rearrangements see review by Zollinger, 1995, Sec. 8.6, and Andraos et al., 1994). 

Wheland intermediate 357 see also Azo coupling reaction, o-complex Wolff rearrangement 80f., 281, 284ff. Woodward-Hoffmann rules 129, 361, 396... 

The rearrangement of acylcarbenes to ketenes is called the Wolff rearrangement (18-8). A few rearrangements in which carbenes rearrange... 

When the Wolff rearrangement is carried out photochemically, the mechanism is basically the same, but another pathway can intervene. Some of the ketocarbene orieinallv formed can undergo a carbene-carbene rearrangement, through an oxi-... 

The diazo ketone can exist in two conformations, called s-(E) and s-(Z). Studies have shown that Wolff rearrangement takes place preferentially from the s-(Z) conformation. 

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