Cyclohexenes addition 4- carbenes

Schollkopf and co-workers have synthesized a number of cyclopropanone acetals by the addition of various sulfur- and oxygen-containing carbenes to ketene diethylacetals (Table 3).26>27> Similarly, cyclopropanone dithioacetals may be prepared by the addition of the Ws-thiomethyl and Ws-thiobenzylcarbenes 12a, b to olefins.29) However, cyclopropanone acetal formation by this method requires double bonds with considerable electron enrichment and the yields are generally low. With unsubstituted olefins such as cyclohexene, the carbenes 12 a, b tend to form dimeric and trimeric products such as 13 and 14, instead of the double bond addition products. 

When tetrabromide 41 was treated with an excess of MeLi/LiBr in cyclohexene as a trap for carbenoids and carbenes, adduct 43 was obtained in 4% yield. In addition, 44 was isolated in 3% yield. The main product, however, was tetrabro-mide 45, whose yield amounted to 32%. The structure of 45 was established by single crystal X-ray crystallography.18... 

Evidence for the generation of these reactive intermediates was obtained from a study of the effect of added cydohexene on the sonication of chloroform. The presence of free radicals in the system was confirmed by the appearance of chlorocydohexane as a product and by the increased rate of decomposition of CHCI3 in the presence of cyclohexene. The increased decomposition rate is a consequence of the presence, in the cavitation bubble, of the alkene which mops up the Cl radical as it is formed and prevents the regeneration of chloroform - i. e. the kinetic steps in Scheme 3.4 are driven from left to right. Carbene intermediates are implicated by the formation of tricyclic compounds such as (1) via dichlorocarbene addition to cydohexene. 

An exo-type cyclization, proceeding through a cycloalkylidene carbene (49 n = 1, 3, 4), was proposed to explain the formation of enynes (50) and (52) from alkynyl lithium species (48). The proposed carbene (49) could be trapped by addition to cyclohexene and the cycloalkyne intermediate (51) was trapped by Diels-Alder reaction with 1,3-diphenylisobenzofiiran. 

Photolysis of 21d (see earlier 21) in alkenes (cyclohexene, 1,1-diphenylethylene) always gave the cyclopropane derivatives 75 by a cis addition of the singlet carbene (64JOC3577) (Scheme 21). 

Reeves and Hilbrich288 have reported the catalysis by pyridines of benzyl ketone alkylation they are less efficient than aliphatic trialkylamines. Reeves and White289 have also described the reaction of alkyl bromides with sodium cyanide, where pyrazine is a better catalyst (99% yield) compared to pyridine (12% yield). Isakawa et al.289 have also carried out addition of dichloro-carbene to cyclohexene under biphasic conditions, using heterocyclic amines as catalysts (e.g., iV-butylpiperidine gives 76% yield). 

The formation of cyclopropane derivatives by photolysis of diazoalkanes in the presence of alkenes is believed to occur by photolytic decomposition of the diazoalkane to yield the carbene, followed by addition of this carbene to the alkene. Cycloaddition of this type has been reported in furan, dihydrofuran, and thiophene.198 Thus, photolysis of ethyl diazoacetate in thiophene yields the bicyclic sulfur heterocycle (215). Alternatively, photolysis of 3-diazo-l-methyl-oxindole (216) in cyclohexene leads to the formation of two isomers which are thought to have the spirocyclopropyl structure (217) photolysis in ethanol yields 3-ethoxy-1-methyloxindole.194... 

These two pieces of evidence show that cyclohexene can add to metal carbene complexes to some extent, but that at low temperature backbiting to give oligomers is preferred to propagation, while at room temperature the product of addition can be trapped, at least for a time, by reaction with norbornene358. 

Besides by these epoxidations, oxaspiropentanes have been prepared through the nucleophilic addition of 1-lithio- 1-bromocyclopropanes to ketones at low temperature. Thus for example, the dibromocyclopropane 96 prepared by addition of dibromo-carbene to cyclohexene 52) underwent metalation with butyllithium to give the lithio-bromocyclopropane 97 which was converted into the oxaspiropentane 98 upon simple addition to cyclohexanone, Eq. (28) 53,54). 

The most common synthetic reaction of carbenes is their addition to double bonds to form cyclopropane rings. For example, dibromocarbene adds to cyclohexene to give an interesting bicyclic compound. 

Of additional interest is the observation that oxacarbenes, such as [85], are not efficiently trapped by typical olefinic substrates to produce cyclopropanes, a reaction which is usually characteristic of carbene species. Yates and Kilmurry, however, have isolated the polycyclic ether [96] (in low yield) from a cyclohexene solution in which oxacarbene [97] was photolytically generated (9,38). 

Deprotonation of carbene complexes followed by treatment with electron-deficient alkenes affords Michael addition products in fair to good yield. Reaction of the chiral pyrrolidine-substituted carbene (6) with 4,4-drmethyl-2-cyclohexen-l-one (7) furnishes fhe alkylkafed product (8) in 95% de (Scheme 14). 

Methyltrioxorhenium has been found to be a universal catalyst for a number of [2-1-1] cycloaddition reactions, including nitrene, carbene, or oxo-atom addition to olefins <2001GC235>. Typically, to increase the chemical yield of the reaction, at least 5 equiv of an olefin is required. As with most nitrene transfer reactions, simple cyclic olefins such as cyclohexene produce a low chemical yield of aziridine. The authors assume that the intermediate of the reaction is a reactive rhenoxaziridine intermediate. 1,2-Dihydronaphthalene provides aziridine 28 in 43% chemical yield under these reaction conditions (Equation 11). 

The mechanism indicates that intermediate formation of a carbene, but tests to confirm the presence of the carbene by possible addition reactions with olefins were negative. The formation of both cyclohexene and cyclohexene are depicted as having the carbene as a common precursor. The experimental data do not, however, rule out the formation of these molecules from diffei ent precursors. For example, cyclohexend could be formed directly from the excited diazirine molecule. Again, further consideration of this point will be deferred until later. 

Obtained from active methylene compounds, such as malonic esters, -0x0 esters and jS-oxo sulfones, iodonium ylides serve as precursors of the corresponding carbenes. Their decomposition by a catalytic amount of a copper salt in the presence of a C-C double bond has been used for inter- and intramolecular cyclopropanation reactions. Thus, reaction of cyclohexene with bis(methoxycarbonyl)methylene(phenyl)iodine(III) under the catalytic action of bis(acetylacetonato)copper(II) yielded dimethyl bicyclo[4.1.0]heptane-7,7-dicarboxylate (1) (38%, mp 91-93°C) in addition to tetrakis(methoxycarbonyl)ethene (41%). ... 

In the case of cyclohexene, cyclopropanation to give 29 was accompanied by the insertion of the carbene into the allylic C-H bond giving 30. Cyclooctene forms both chloro- and bromo(trifluoromethyl)carbene addition products 31 and 32. Both reactions were rather slow. ... 

Indeed, the reaction of an equimolar quantity of bromodichloromethyl(phenyl)mercury with alk-2-enoic acids affords the dichloromethyl esters. Dichlorocyclopropanation is only possible if a second mole of carbene source is used (see Houben-Weyl, Vol. 4/3, pp 178-179). Competition between acetic acid and cyclohexene for dichlorocarbene indicates that the acid is considerably more reactive.Furthermore, dichloromethyl 2,2-dichlorocyclopropane-carboxylates cannot be hydrolyzed to the corresponding acids. To avoid all of these difficulties, addition of dichlorocarbene, generated under nonhydrolytic conditions using dichloro-halomethyl(phenyl)mercury, to the bromides of alk-2-enoic acids is possible. 

The reactions of aryl-substituted carbenes are extensively covered in Houben-Weyl Vol. E 19b, pp 824-1021, where procedures for all typical carbene transfer methods are reported. The simple diastereoselectivity is highly dependent on the carbene source and the reaction conditions, as demonstrated by the additions of phenylcarbenoids, generated by different methods, to cyclohexene. The highest endo selectivity is obtained with the diiodo(phenyl)methane/diethylzinc reagent3. Other cyclic or acyclic olefins show a similar moderate to high preference for endo- or cw-cyclopropane formation. 

Phenylsulfinyl)diazomethane decomposes at 0°C to afford (phenylsulfinyl)carbene which can be trapped by cyclohexene to provide 7-(phenylsulfiiiyl)bicyclo[4.1.0]heptane with excellent exo selectivity2. On the other hand, the addition of (phenylsulfonyl)carbene photochemically produced from (phenylsulfonyl)diazomethane, gives 7-(phenylsulfonyl)bicyclo[4.1.0]heptane rather unselectively as an exojendo-mixture3. 

Photoexcitation of cycloalkenes introduces additional features because the ring limits the extent to which the double bond can twist. Cyclohexene, cycloheptene, and cyclooctene give rise to ring contraction and carbene insertion products. 

The reaction of carbenes with aromatic hydrocarbons is related to that with alkenes. Doering and Knox (1950, 1953) investigated this reaction using benzene as substrate even before their work with cyclohexene. They observed, however, ring expansion to give cycloheptatriene besides toluene (8-3, X = H). Norcaradiene as an intermediate was isolated only much later in the addition of dicyanomethylene... 

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