Carbenes addition, alkenes stereospecificity

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. 

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. 

A. Carbene or Carbenoid Addition to Stereospecifically Deuterated Alkenes... 

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... 

The stereospecific addition to alkenes is consistent with (difluoromethyl)fluorocarbene being generated in the singlet state, Adducts of this carbene with alkenes were observed during the pyrolysis of trimethyl(l,l,2,2-tetrafluoroethyl)silane. ... 

Reaction of bromofluorophenylmethane (for a preparation see ref 118) and potassium tert-butoxide with an alkene afforded l-fluoro-l-phenylcyclopropanes (Houben-Weyl, Vol.4/3, p233 Vol. E19b, p980). To identify the reacting species, e.g. carbene or carbenoid, the reaction was carried out without and with an equimolar amount of 18-crown-6. ° Alternatively, chlorofluorophenylmethane, in place of the bromo derivative, can be used. Reactions with bromofluorophenylmethane were performed at 25 °C (sealed tube), whilst those with chlorofluorophenylmethane at 60-80 °C. Addition of fluoro(phenyl)carbene to alkenes is at least 98% stereospecific e.g. formation of . ... 

Generation of chloro(2-furyl)carbene and chloro(2-thienyl)carbene from 2-dichloromethyl-furans 1 or 2-diehloromethylthiophenes 2 and a base, followed by addition to an alkene, gave l-chloro-l-(2-furyl)- or l-(2-thienyl)cyclopropanes, respectively "(for earlier work, see Houben-Weyl, Vol. E19b, p 1001). The reactions were carried out using potassium /crt-butoxide as the base with, or without, 18-crown-6, or solid potassium hydroxide and a catalytic amount of benzyltriethylammonium chloride (TEBAC) (solid-liquid variant of a phase-transfer catalytic system ). Under both conditions, yields of cyclopropanes were usually good, yet the phase-transfer catalytic system seems to be more convenient from a practical point of view. Addition of the above described carbenes to alkenes was stereospecific. 

Alkynyl-l-chlorocyclopropanes are formed from l-(bromochloromethyl)alkynes, the corresponding bromoalkynyl derivatives are not detected. (Z)-But-2-ene undergoes stereospecific addition of alkynylhalocarbenes which implies they react in a singlet state. None of the adducts resulting from the addition of isomeric (haloethynyl)alkyl(or aryl)carbene to alkenes are found. 

Stereospecificity (or lack of it) in the addition o a carbene to an alkene 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, butthe fact that an addition is stereospecific doesn t mean that the carbene must be a... 

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. 

Until the last decade, product studies formed the main evidence for carbene formation singlet carbenes formed cyclopropanes from alkenes stereospecifically, while triplet carbenes formed cyclopropanes non-stereospecifically. Formation of a cyclopropane (though not by addition to an alkene) via a carbocation route was demonstrated and, more recently, it has been shown that p values for insertion-addition selectivity and for cyclopropanation stereoselectivity vary as to photochemical or thermal generation of the carbene. The authors of this latter study suggest that a ground state diazo compound could be masquerading as a carbene in its thermal reaction with olefins, possibly by electrocyclic... 

Figure S.7 Mechanism of stereospecific addition of carbene to alkene.

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. 

Surprisingly, the critical experiment has been done infrequently over the last one-half of a century The requirements for an experiment that truly speaks to the issue at hand are that one be able to see the results of addition of both spin states of a single carbene, and these requirements rarely have been met. For example, the direct irradiation of methyl diazomalonate leads to the stereospecific addition expected of a singlet carbene, whereas the photosensitized decomposition of the diazo compound leads to formation of the triplet carbene and loss of the stereochemical relationship originally present in the reacting alkene. Rotational equilibration in the intermediate seems to be complete, as it makes no significant difference whether cis or trans alkene is used as starting material (Scheme 7.9). ... 

In marked contrast, we used the cyclopropanation reaction of (phosphino)(silyl)-carbene (la) with methyl acrylate to demonstrate the carbene nature of our compound. More recently, we studied in detail the stereochemistry of this type of reaction.The (phosphino)(silyl)carbene (la) reacted efficiently with 3,3,4,4,5, 5,6,6,6-nonafluorohex-l-ene and (Z)- and ( )-2-deuteriostyrene giving the corresponding cyclopropanes in good yields. The stereochemical outcome was such that all monosubstituted alkenes gave exclusively the syn isomer (with respect to the phosphino group), and the addition of disubstituted alkenes was totally stereospecific (Scheme 8.16). 

Product Studios. Alkenes are known as diagnostic reagents for spin state of reacting carbenes. Thus, the reaction of a singlet carbene with an olefin usually results in the formation of a cyclopropane through stereospecific addition to the C—C double bond, while a triplet carbene gives rise to a nonstereospecific addition product (see Section 7). 

Cyclopropane formation occurs from reactions between diazo compounds and alkenes, catalyzed by a wide variety of transition-metal compounds [7-9], that involve the addition of a carbene entity to a C-C double bond. This transformation is stereospecific and generally occurs with electron-rich alkenes, including substituted olefins, dienes, and vinyl ethers, but not a,(J-unsaturated carbonyl compounds or nitriles [23,24], Relative reactivities portray a highly electrophilic intermediate and an early transition state for cyclopropanation reactions [15,25], accounting in part for the relative difficulty in controlling selectivity. For intermolecular reactions, the formation of geometrical isomers, regioisomers from reactions with dienes, and enantiomers must all be taken into account. 

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