Carbenoids addition

In addition, carbenoid insertion of aliphatic C-H bond can be achieved in the presence of iron(III) porphyrin as catalyst. A benzylic C-H insertion product was obtained along with the arene C-H insertion product in a ratio of about 5 1 when p-xylene was used as substrate and solvent (eq 57). 

Treatment of geminal dihalocyclopropyl compounds with a strong base such as butyl lithium has been for several years the most versatile method for cumulenes. The dihalo compounds are easily obtained by addition of dihalocarbenes to double--bond systems If the dihalocyclopropanes are reacted at low temperatures with alkyllithium, a cyclopropane carbenoid is formed, which in general decomposes above -40 to -50°C to afford the cumulene. Although at present a number of alternative methods are available , the above-mentioned synthesis is the only suitable one for cyclic cumulenes [e.g. 1,2-cyclononadiene and 1,2,3-cyclodecatriene] and substituted non-cyclic cumulenes [e.g. (CH3)2C=C=C=C(CH3)2]. 

It is also possible to convert carbonyl groups into oxirane rings with cenain carbenoid synthons. The classical Darzens reaction, which involves addition of anions of a-chloroacetic esters, has been replaced by the addition of sulfonium ylides (R. Sowada, 1971 C.R. Johnson, 1979). 

Cyclopropane rings are opened hydrogenolytically, e.g., over platinum on platinum dioxide (Adam s catalyst) in acetic acid at 2 - 4 bars hydrogen pressure. The bond, which is best accessible to the catalyst and most activated by conjugated substituents, is cleaved selectively (W.J. Irwin, 1968 R.L. Augustine, 1976). Synthetically this reaction is useful as a means to hydromethylate C—C double bonds via carbenoid addition (see p. 74f. Z. Majerski, 1968 C.W. Woodworth, 1968). 

Other potential synthetic routes to these unsaturated aziridine derivatives which involve the addition of nitrenes to allenes <75JOC224), carbenes to imines with subsequent hydrolysis <67JA362), and of carbenoid species to ketenimines <76TL1317,79TL559) have been investigated but are collectively of little or no preparative value. 

In addition to the synthesis of heterocycles, the Corey-Chaykovsky reaction bestows an entry to carbocycles as well. The reaction of (trialkylsilyl)vinylketene 89 with substituted ylide 90 led exclusively to rrans-4,5-dimethyl cyclopentenone 91. The substituted ylide 90 here serves as a nucleophilic carbenoid reagent in the formal [4 +1] annulation reaction. 

The possibility of a radical mechanism is supported by the observation of the accelerating effect of molecular oxygen on the cyclopropanation. Miyano et al. discovered that the addition of dioxygen accelerated the formation of the zinc carbenoid in the Furukawa procedure [24a, b]. The rate of this process was monitored by changes in the concentration of ethyl iodide, the by-product of reagent formation. Comparison of the reaction rate in the presence of oxygen with that in the... 

The formulation of an additive for zinc carbenoid cyclopropanation that meets these criteria is severely compromised by the by the inherent Lewis acidity of the zinc atom. This Lewis acidity is required for methylene transfer and plays a major... 

For a reaction as complex as catalytic enantioselective cyclopropanation with zinc carbenoids, there are many experimental variables that influence the rate, yield and selectivity of the process. From an empirical point of view, it is important to identify the optimal combination of variables that affords the best results. From a mechanistic point of view, a great deal of valuable information can be gleaned from the response of a complex reaction system to changes in, inter alia, stoichiometry, addition order, solvent, temperature etc. Each of these features provides some insight into how the reagents and substrates interact with the catalyst or even what is the true nature of the catalytic species. 

Having observed that (i) the zinc carbenoid must be formed prior to addition of the alcohol or sulfonamide and (ii) that the zinc alkoxide should be preformed in order to obtain high selectivity, the importance of the zinc sulfonamide could be assessed (Fig. 3.14). In this sub-set, flask A contains the preformed zinc alkoxide, flask B contains the promoter solution and flask C contains the preformed zinc carbenoid. In sub-protocol Ilia, flasks A and C are combined prior to addi-... 

Although the previous protocol suggests it is not necessary to deprotonate the sulfonamide prior to exposure to the zinc carbenoid, a experimentally simpler procedure can be envisioned wherein the alcohol and promoter are deprotonated in a single flask (Fig. 3.15). In protocol IV, the alcohol and promoter are combined in flask A and are treated with diethylzinc, thus forming the zinc alkoxide and zinc sulfonamide. In sub-protocol IVa, this solution is transferred to flask C which contains the zinc carbenoid. Sub-protocol IVb represents the reversed addition order. Sub-protocol IVa is not only found to be the superior protocol in this sub-set, it is found to out-perform all of the previous protocols Despite the persistence of the induction period, a large rate enhancement over the uncatalyzed process is observed. This considerable rate enhancement also translates to a reduction in the overall reaction time when compared to sub-protocols la and Ilia. Selectivity rises... 

Fig. 3.25 Comparison of insertion and addition reactions of zinc carbenoids. [Bernardi, F. Botti-ni, A. Miscione, G.P. J, Am. Chem. Soc. 1997, 119, 12300. Reprinted with permission from The American Chemical Society]...

Those reactions that have found general use for the preparation of aziridines can be grouped into two broad classes addition and cyclization processes, and each of these categories can be further divided. Addition processes can be classified as being C2+N1 reactions (addition of nitrenes, or nitrene equivalents [ nitrenoids ], to alkenes Scheme 4.1) or (J N1+C1 reactions (addition of carbenes or carbenoids to imines Scheme 4.2). 

C1N1 + C-t reactions addition ofcarbenes, or carbenoids, to alkenes Scheme 4.2... 

The synthesis of aziridines through reactions between nitrenes or nitrenoids and alkenes involves the simultaneous (though often asynchronous vide supra) formation of two new C-N bonds. The most obvious other alternative synthetic analysis would be simultaneous formation of one C-N bond and one C-C bond (Scheme 4.26). Thus, reactions between carbenes or carbene equivalents and imines comprise an increasingly useful method for aziridination. In addition to carbenes and carbenoids, ylides have also been used to effect aziridinations of imines in all classes of this reaction type the mechanism frequently involves a stepwise, addition-elimination process, rather than a synchronous bond-forming event. 

The Addition of Carbenes and Carbenoids to Double and Tripie Bonds... 

Which isomer is predominantly formed depends on R, R, and on the method by which the carbene or carbenoid is generated. Most studies have been carried out on monosubstituted species (R = H), and in these studies it is found that aryl groups generally prefer the more substituted side (syn addition) while carbethoxy groups usually show anti stereoselectivity. When R = halogen, free halocarbenes show little or no stereochemical preference, while halocarbenoids exhibit a preference for syn addition. Beyond this, it is difficult to make simple generalizations. 

The reactive intermediates under some conditions may be the carbenoid a-haloalkyllithium compounds or carbene-lithium halide complexes.158 In the case of the trichloromethyllithium to dichlorocarbene conversion, the equilibrium lies heavily to the side of trichloromethyllithium at — 100°C.159 The addition reaction with alkenes seems to involve dichlorocarbene, however, since the pattern of reactivity toward different alkenes is identical to that observed for the free carbene in the gas phase.160... 

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