Doering reaction

In the following decades, chemists tried to utilize more and more the knowledge on reactions which had already been gained. A number of landmark syntheses represent the change to modern chemistry, such as the synthesis of the estrogenic steroid equilenin (W. Bachmann, 1939), of pyridoxine (K. Folkers, 1939), and of quinine (R.B. Woodward, W. von E. Doering, 1944) [23]. 

Direct evidence for the existence of dichlorocarbene, by trapping with a suitable substrate, was obtained by Doering and Hoffmann in 1954. Dichlorocarbene was shown to add in a characteristic manner to the double bond of cyclohexene to give dichloronorcarane (1) in 59% yield similar adducts were obtained with other olefins. Bromo-form imderwent an analogous reaction in the presence of olefins to give... 

As another example, the tropylium ion [3 ], which is stabilized by virtue of the 67t electrons spread over a heptagonal sp hybridized carbon framework [Hiickel s (4n 4- 2)v rule with = 1], is also unstable in the gas phase. Its formation from toluene or the benzyl cation has been a long-standing problem in organic mass spectrometry, and the reaction mechanism and energetics have recently been exhaustively discussed (Lif-shitz, 1994). It was, however, isolated as the bromide salt by Doering and Knox (1954, 1957), and was the first non-benzenoid aromatic carbocation. 

The Doering-Moore-Skattebol method including a cyclopropylidene-allene rearrangement is often used for the synthesis of allenes. However, the reaction conditions applied are often not compatible with acceptor substituents. One of the rare exceptions is the transformation 76 —> 77 (Scheme 7.11) [122]. The oximes 77 are not accessible by the classical route starting from allenyl ketone and hydroxylamine (see Section 7.3.2). 

This chapter will cover only reactions in which the isomerization to the allene starts from a stable molecule and not from a reactive intermediate generated in situ by reactions which are not isomerizations, such as the Doering-Moore-Skattebol reaction or free carbenes. Metallotropic rearrangements also will not be covered many of these reactions can be found in Chapter 9. Furthermore, the allene should be the final product of the reaction and not only a transient species leading to other products (see, for example, Chapters 6 and 20). 

The occurrence of the reaction can however be detected by N.M.R. spectroscopy (for a detailed discussion of the observed spectra, see Doering and Roth, 1963). It is estimated that 3,4-homotropilidene undergoes this rearrangement about 1000 times per second at 180° C and about once per second at — 60° C. These data require further verification since they lead to highly improbable values for the A factor and for the energy of activation of the reaction. At much higher temperatures the compound isomerizes irreversibly to tetrahydropentalene ... 

The photolysis or thermolysis of diazo compounds results in the formation of carbenes. These reactions were identified as early as 1901 by Hantzsch and Lehmann D and Staudinger and Kupfer who decomposed diazomethane photochemically and thermally, respectively. The subsequent work of Hine 3) and Doering ) started the era of carbene chemistry. Excellent reviews of the chemistry of carbenes are available 5-27),... 

Cyclic allenes have previously been obtained only admixed with the isomeric acetylenes. The present two-step synthesis is a practical method for the preparation of cyclic allenes, and at the same time it describes a general method for the preparation of allenes. It is based on the original work of Doering and co-workers. Examples of the reaction sequence above are known in which allenes are not produced, or they represent only a part of the reaction products. A one-step synthesis of 1,2-cyclonona-diene has been reported. ... 

Looking at Schemes 4 and 5, it is obvious that Woodward-Doering s synthetic route suffered from the lack of stereocontrol, which led to the production of their precursors of homomeroquinene target compound as a mixture of stereoisomers. The fact that the yield of such a transformation was not clearly determined, in addition to the anticipated difficult separation of the four isomers obtained at the end of the reaction (cf. Rabe-Kindler reaction), rendered this reaction commercially unpractical. Moreover, it is well accepted that Woodward and Doering never physically produced any quinine in their lab, and the success of their method is based on the assumption that Rabe and Kindler partial synthesis was a fact. This would be the center of the controversy when Stork later characterized what he called the quasi-universal impression that Woodward and Doering achieved the total synthesis of quinine as a widely believed myth . The whole story is very juicy and interested readers should refer to the amazing review published in Angewandte Chemie by Seeman in 2007. Nevertheless, in 2008, Smith and Williams successfully revisited the Rabe-Kindler conversion... 

For reviews on the transformation of dibromocyclopropanes to allenes (see so-called Doering-Skattebol-Moore reaction) see (a) Hopf H (1980) In Patai S (ed) The Chemistry of Ketenes, Allenes and Related Compoimds Wiley, New York, Part 2, Chapter 2, p 779 ... 

Evans Ablow (Ref 66, p 147) stated that Zel dovich, von Neumann Doering defined the detonation wave as a reaction initiated by a shock. Evans ... 

Philicity. A principal feature of the carbene-alkene addition reaction (Scheme 7.1) is the carbene s phihcity, that is the electronic character of its selectivity or response to the alkene s substituents. Early work of SkeU and Garner and Doering and Henderson showed that CBr2 and CCI2 preferentially... 

In 1956, Doering et al. reported that methylene (CH2) inserted into the C H bonds of pentane, 2,3-dimethylbutane, and cyclohexene with no discrimination (other than statistical) between chemically different sites CH2 was classed as the most indiscriminate reagent known in organic chemistry. Doering and Kirmse also demonstrated that the C—H insertion reactions of CH2 in solution were direct, single barrier concerted processes with transition states that could be represented as 27 (Fig. 7.12). In particular, they did not proceed via initial H abstraction to give radical pair intermediates that subsequently recombined. (Triplet carbene C H insertions, however, do follow abstraction-recombination, radical pair mechanisms, as demonstrated in classic experiments of Closs and Closs and Roth (see Chapter 9 in this volume). 

Phenylazide was first synthesized by Greiss in 1864. In 1912, Wolf studied the pyrolysis of phenyl azide in aniline. The product of this reaction, azepine (27), was identified by Huisgen and co-worker in 1958. Eight years later. Doering and Odum demonstrated that azepine (27) is formed upon photolysis of phenylazide in diethylamine and in 1977 Carroll et al. ° discovered the formation of 28 upon photolysis of phenyl azide in the presence of ethanethiol. 

Sundberg and co-workers studied the photochemistry of phenyl azide by conventional flash photolysis in 1974. They detected the transient UV absorption of ke-tenimine 30 and measured its absolute rate constant of reaction with diethylamine to form the IH azepine, which subsequently rearranges to Doering and Odum s 3H-azepine (27). ... 

Secondly, Leyva et al found that the solution phase photochemistry of phenylazide (PA) was temperature dependent. Photolysis of PA in the presence of diethylamine at ambient temperature yields azepine 2, first prepared by Doering and Odum. Lowering the temperature suppresses the yield of 2 and encomages the formation of azo compound. Thus, high temperatures favor reactions of singlet state intermediates, whilst low temperatures favor reactions associated with triplet phenylnitrene. 

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