Seyferth procedure

The one-step Seyferth procedure offers an alternative to the Corey -Fuchs sequence. After a Horner-Wadsworth-Emmons olefmation of an aldehyde 37 to an unsaturated diazo compound 38. elimination of nitrogen and [1,2]-rearrangement of the resulting vinylcarbene 39 leads here as well to a Cy-extended terminal alkyne 40.19... 

Fig. 11.28. Aldehyde alkyne chain elongation via [1 -rearrangement of a vinyl carbene (Seyferth procedure). First, a Horner-Wadsworth-Emmons olefination of the aldehyde is carried out to prepare alkene A. Upon warming to room temperature, alkene A decomposes and gives the vinyl carbene B. From that, the alkyne is formed by way of a [1,2]-rearrangement.

Studies by the submitters have indicated that the procedure reported here is the preferred method for the preparation of bicyclo[3.2.1]octan-3-one. It employs readily available, inexpensive reagents, and the overall yield is good. In addition, the method can be used for the synthesis of the difficultly accessible next higher homologues of bicyclo[2.2.2]oct-2-ene as well as for derivatives of norbornene. Bicyclo[3.2.2]nonan-3-one and l-methylbicyclo[3.2.1]octan-3-one have been prepared by a similar route6 in 60% and 47% yields, respectively (based on adduct). However, the preferred procedure for the formation of the dichlorocarbene adduct of bicyclo[2.2.2]oct-2-ene is that of Seyferth using phenyltrichloromethylmercury. Even in this case the overall yield is moderate (37%). 

Catalyst-mediated decomposition of diazo compounds in the presence of C=S compounds has found application for the preparation of thiiranes in homogeneous systems (68,110,111). Recently, a convenient procedure for the preparation of geminal dichlorothiiranes from nonenolizable thioketones and chloroform under Makosza conditions was reported (112). Another approach to 2,2-dihalogenated thiiranes (e.g., 2,2-difluoro derivatives) involves the thermolysis of Seyferth reagents in the presence of thioketones (113,114a). Nucleophilic dimethoxycarbene was shown to add smoothly to adamantanethione to provide a unique approach to a thiiranone (5, 5 )-dimethylacetal (114b). 

Chemical Modification. Reactions on the macromolecular polyenes were carried out by procedures described previously (3, 4). PhHgCBr3 is obtained by a modification of Seyferth s method (21) from PhHgBr and HCBr3 in presence of a base. Yields similar to those reported in the literature are obtained more easily by replacing the complex (tert-BuOK— tert-BuOH) with a solution of sodium tert-amylate in benzene as prepared by Conia (24). This reagent was, in fact, used systematically in place of potassium tertf-butylate it is easier to use and can be prepared completely free of alcohol. 

Seyferth concludes that phenyl(lrifluoromethyl)mercury is an excellent precursor for difluorocarbene. In the general procedure, 1 molar eq. of CeHjHgCFj, 2.5-3.0 molar eq. of well-dried sodium iodide, and 3.0 molar eq. of the dried olefin are used (N2). Benzene is distilled into the reaction flask directly from sodium benzophenone ketyl. The reaction mixture is stirred and heated at reflux under Nj for 12 18 hr. Filtration removes phenyl mercuric iodide and Nal and Nab" the gem-difluorocyclo-propanes are isolated by distillation or by gas chromatography, usually in good yield. 

In a procedure described by Seyferth the reagent is prepared by transme talation of methyllithium with tribenzyltin chloride, readily accessible by direct reaction of benzyl chloride with metallic tin in anhydrous medium. Benzyllithium is produced... 

When vinyl- or a-alkoxyalkyltin compounds are exposed to alkyllithium, unique hn-hfhium exchange occurs, conveniently generating organolithium species that are otherwise difficult to obtain. Although it is a long time since the discovery of these procedures by Seyferth [2] and ShU [3], respechvely, their usefulness has never faded. Recent apphcahons will be covered in Sechon 12.3. 

The first two steps are well known and proceed in about 60% yield. Conversion of the cyclopropyl bromide into the cyclopropyllithium is carried out with lithium in diethyl ether according to the procedure of Seyferth and Cohen.2 The yield is nearly quantitative. The final step, oxygenation, is performed with C02-free oxygen at— 71°, followed by hydrolysis with saturated ammonium chloride. Yields are generally 50-70%. 

Japanese chemists have now reported the alkylation of 1-lithiocy do propyl bromides, prepared by treatment of ge/n-dibromocyclopropanes with n-butyl-lithium, by reaction with an alkyl halide. They were able to prepare syn-1-methyl-anfi-7-bromonorcarane (3) as the exclusive product by addition of methyl iodide to (2), prepared essentially by Seyferth s procedure. As applied to other g-ew-dibromocyclopropanes, the reaction is usually stereoselective rather... 

Seyferth et al. [1] give well-detailed descriptions for the generation of a number of lithium halocarbenoids from geminal dihalocyclopropanes. In their procedures, a solution of BuLi in hexane is added to a mixture of the dihalo compound and THF kept between — 90 and — 100 °C. According to Villieras [2], lithium bromide... 

In Seyferth s procedures [1], which do not use lithium bromide, the BuLi solution is allowed to run down the cold glass wall before it makes contact with the solution of the substrate. The reason for applying this technique is probably also to minimize local heating effects. 

The first successful syntheses of phosphorus-containing diazoalkyl compounds (1) appear to have been reported independently by two groups of workers. Petzold and Henning employed a method presently described as that of diazo transfer, in which an active methylene compound, as its anion, is treated with an aromatic sulphonyl azide. Seyferth et al on the other hand, reported on a development to the Bamford-Stevens reaction, in which a carbonyl/7-toluenesulphonylhydrazone is treated with a base. Both methods thus depend on modifications to compounds with existing phosphorus-carbon bonds, as do other procedures which have since been developed. 

To avoid the direct manipulation with hazardous azides, methods using Cu(I)situ generation of azides were developed as one-pot procedures, for example, with substitution reaction of alkyl hahdes by NaN3 [493] or with nitrosation of aromatic primary amines by tBuONO followed by trimethylsilyl azide [494]. Vice versa, the alkyne component has been generated in situ, for example, by sequential Seyferth-Gilbert reaction (homologation of aldehydes with diazophosphonates) and reaction with azides in a Cu(l)-catalyzed cycloaddition [495]. 

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