Stereospecific carbene addition

There is a limitation to the use of stereospecificity of addition as a diagnostic test for singlet or triplet carbenes.When carbenes are generated by photolytic methods, they are often in a highly excited singlet state. When they add to the double bond, the addition is stereospecific but the cyclopropane formed carries excess... 

The stereospecificity of addition suggests a singlet(10) carbene although the ground state of cyclopentadienylidene is known to be a triplet. Attempts to produce a triplet species, which would be expected to react nonstereospecific-ally, in a 4-methyl-cw-2-pentene matrix at 77°K or by dilution of mixtures of the azo compound and olefin with hexafluorobenzene or octafluorocyclo-butane (inert diluents) were unsuccessful. It was concluded that the singlet carbene produced upon photolysis reacts more rapidly with the olefinic... 

Finally, addition reactions of the isolable phosphasilylcarbenes (13) to such electron-poor substrates as methyl acrylate, C4F9CH=CH2, and styrene afford cyclopropanes. The additions of 13a to (E)- or (Z)-p-deuteriostyrene are stereospecific, and the competitive additions of 13b to ring-substituted styrenes exhibit nucleophilic selectivity, consistent with singlet, nucleophilic carbene addition (Fig. 7.8). ... 

Problem 9.29 (a) Use the following observations to discuss stereospecificity of carbene addition, (b) Suggest mechanisms for addition of (i) singlet and (ii) triplet carbenes to alkenes. 

Carbenes are much more reactive toward carbon-carbon double bonds than toward single bonds. Without doubt the most useful feature of a elimination is that it provides a practical route to cyclopropanes and cyclopropenes by [2 + 1 ] cycloaddition of carbenes to double or triple bonds. These additions are stereospecific suprafacial additions if they involve singlet carbenes, but can give mixtures with triplet carbenes ... 

Stereospecificity (or iack of it) in the addition of a carbene to an aikene can be a good test of Whether the carbene reacts as a singlet or triplet lack of stereospecificity in a carbene addition almost certainly indicates that a triplet carbene is involved, but the fact that an addition is stereo specific doesn t mean that the carbene must be a... 

The dilution technique makes use of the different concentration dependence of the S—T conversion (a) and the carbene addition to the olefin (/S). The decay of the metastable singlet state is unimolecular, while the stereospecific addition rate is first-order in olefin concentration 78). The dilution technique has not yielded a common ratio in the experiments with cis- or iraws-butene and 2c (see Table 11). Extrapolation of the data to infinite dilution gives a product ratio of 0.16, suggesting that... 

IS the most popular, one-step method for m ag fluorinated cyclopropanes and cyclopropenes a-Fluorocarbenes are particularly well behaved, because they all have singlet ground states [/, 2] and therefore usually add stereospecifically to alkenes and do not insert into C-H bonds competitively with addition Moreover, quantitative competition studies of carbene additions to alkenes near room temperature show that a-fluorocarbenes are more selective than other a-halocarbenes, with difluorocarbene being the most selective electrophihc carbene known [3, 4] The relative selectivities, however, can be quite temperature dependent [5, d] The numerous preparations and cycloaddmons of fluorocarbenes have been reviewed thoroughly [7, 8 9,10 ... 

Carbene addition occurs in a syn fashion from either side of the planar double bond. The relative position of substituents in the alkene reactant is retained in the cyclopropane product. Carbene addition is thus a stereospecific reaction, since cis and trans alkenes yield different stereoisomers as products, as illustrated in Sample Problem 26.4. 

The cyclopropanation reaction of simple alkenes appears to proceed via stereospecific 5yn-addition of a Zn-carbenoid (carbene-like species) to the double bond without the involvement of a free carbene. 

With respect to the arylcarbenes, however, the carbene addition is not stereospecific the aryl-cyclopropanes are generally formed as mixtures of diastereomers. In almost all cases reported, the sj -isomer predominates, and this is the case even when the corresponding uw/z-isomer is far less sterically crowded. Thus, when 1-naphthylcarbene reacted with cyclopentene, the corresponding cyclopropane 6-(l-naphthyl)bicyclo[3.1.0]hexane (4) was obtained in 62% yield with endojexo ratio of 84 16. ... 

Some arylcarbenes, prepared by photodecomposition of the corresponding diazo compounds, undergo intersystem crossing so effectively that the alkenes present are mainly attacked by triplet-excited carbenes. This type of reactivity has, in particular, been associated with nitro-substituted arylcarbenes. The reaction between photochemically generated 4-nitrophenyl-carbene and (Z)- and ( )-but-2-ene, which has been studied in particular detail, has shown that nonstereospecific carbene addition may become just as important as the stereospecific reaction. ... 

The spin state of the reacting acylcarbene has a decisive influence on the reactivity of this short-lived species (Houben-Weyl, Vol.4/5b, pp 1158-1257 Vol. E19b, pp 1052 and 1231 refs 67,100-103). As far as cyclopropanation is concerned, carbene addition to a (Z)- or ( )-alkene can occur with retention or with loss of the stereochemical relationship present in the alkene (stereospecific and nonstereospecific cyclopropanation, respectively). Singlet carbenes add to C-C double bonds in a concerted manner, and therefore, stereospecifically. In contrast, a triplet carbene undergoes stepwise addition via an intermediate triplet 1,3-diradieal. Sinee spin-in-version must occur before ring closure of the latter species, the extent to which stereospecificity... 

Double dehydrohalogenations have been used recently in the synthesis of a number of bis(methylene)triangulanes (Table 5). Typically, the starting dihalides are prepared by a sequence of cyclopropanation with chloromethylcarbene and monodehydrochlorination, in which a tetrahydropyranyl ether serves as the source of the bromide or iodide moiety (see Section 5.2.2.1.1.1.). The double elimination is carried out with potassium ier/-butoxide in dimethyl sulfoxide at or near room temperature, and gives low to moderate yields of bis(methyl-ene) products. In some cases mixtures of diastereomers were obtained due to the lack of stereospecificity of the preceding carbene addition to the double bond which consequently led to the presence of a mixture in the starting material. The procedure is illustrated by the synthesis of 1,4-bis(methylene)spiropentane (2). ... 

The full paper describing Mori s synthesis of lineatin (296) (Vol. 4, p. 489, Ref. 263) has been published. After converting the lactone 329 to ( )-lineatin using a [2 + 2] cycloaddition, Slessor et al. followed another route from the same lactone 329, which is readily available by the Lewis acid-catalyzed addition of ketene to mesityl oxide. The route is shown in Scheme 25. In this scheme, the mixture arising from the carbene addition is not separated because, at the stage of the epoxide formation, only the major (desired) isomer 330 was isolated, the other being thermally unstable. The exo alcohols obtained in small amounts after the borohydride reduction (step h) were not isolated. To obtain the natural isomer of lineatin [( + )-(l/ ,4S,5/ ,7R)-296] the alcohol 331 was resolved with (—)-(r)-l-(l-nephthyl)ethyl isocyanate/triethylamine. The first stereospecific chiral synthesis of (+)-lineatin (296) started from D-ribonolactone (332), and is illustrated (in somewhat abbreviated form) in Scheme 26 it proceeded in 2.7% overall yield. °... 

Singlet carbene (concerted mechanism - stereospecific syn- addition)... 

An important characteristic reaction of carbenes is addition to an alkene to yield a cyclopropane . This reaction allows distinction between singlet and triplet forms, since addition of the singlet form is stereospecific while addition of the triplet form is not . However, rates of reaction of carbenes and alkenes varied widely so the reaction was a useful rather than definitive diagnostic test. 

Carbene 42 adds to a variety of electron deficient olefins, and even to styrene " with -substituted styrenes, the nucleophilicity of these additions can be observed (for 42 with cyclohexyl replacing isopropyl). [117] Moreover, additions of 42 to Z- and ii-2-deuteriostyrene are stereospecific with respect to the styrene substituents, as anticipated for singlet carbene additions. [117] Thus, the isolable phosphinosilylcarbenes are nucleophiles, but retain the essential reactivity expected of such carbenes. 

The stereospecificity of carbene additions has been widely used in experiments designed to determine the multiplicity of a carbene generated under given conditions. Stereospecific addition is taken as evidence for the involvement of the singlet species. The alternate result, formation of a mixture of the possible isomers, requires additional information for complete interpretation. Lack of stereospecificity implies some triplet carbene, but permits simultaneous involvement of the singlet species. 

Noyori and co-workers have continued their investigations of the nickel-promoted ring-opening of bicyclobutanes retro-carbene addition gives allylcarbene-nickel intermediates which can be trapped stereospecifically by electrophilic olefins. Nickel-catalysed opening of 3,3-dimethylcyclopropene evidently follows a very similar course whilst interactions of rhodium and nickel with vinylcyclo-propanes and of palladium(ii) with Feist s acid involve metal-alkenyl intermediates. 

Because the additions are normally stereospecific with respect to the alkene, if an open-chain intermediate is involved, it must collapse to product at a rate more rapid than that of single-bond rotations, which would destroy the stereoselectivity. Entries 5-10 in Scheme 10.5 are examples of transition-metal-catalyzed carbene addition reactions. 

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