Carbene reaction with lone pairs

Carbenes are electron-deficient intermediates, capable of reacting with organic compounds in several ways. Typical reactions of uncomplexed carbenes include cyclopropanation, C-H insertion, and reaction with lone pairs to yield ylides (Figure 1.2). 

The reactions of carbenes, which are apparently unique in displaying electrophilic character in strongly basic solutions, include substitution, addition to multiple bonds, and co-ordination with lone pairs of electrons to form unstable ylides. This last reaction is of obvious relevance to a consideration of the reactions of heterocyclic compounds with carbenes and will be summarized. 

Tungsten alkynyl Fischer carbene complexes are excellent dienophile partners in the classical Diels-Alder reaction with 1-azadienes (see Sect. 2.9.2.1). On the contrary, the chromium-derived complexes exhibit a different behaviour and they react through a [4S+3C] heterocyclisation reaction to furnish azepine derivatives [116] (Scheme 68). The reaction is initiated by a 1,2-addition of the nitrogen lone pair to the carbene carbon followed by a [l,2]-Cr(CO)5 shift-pro-... 

The enthalpies of reaction for nucleophilic carbencs depend on the stereoelec-tronic properties of the ligands affecting the availability of the carbene lone pair. An example of electronic influence is the 3.5 kcal/mol enthalpy difference between the isosteric pair IMes and IMesCI that shows the electron-withdrawing nature of Cl compared to H. This trend again is in line with electron donor/withdrawing ability of arene substituents. The effect in this la.st case is a long range electronic... 

Push-spectator carbenes of the type 31 (R, R = alkyl) were synthesized and reacted with various Lewis Acids to compare the reactivity of the phosphorus and carbene centers. Two such reactions are shown in Scheme 7.11. From an X-ray structural analysis, the phosphorus substituent was shown to act as a spectator, leaving its lone pair available to react in a Lewis basic manner. When carbene 31 was reacted with BF3, only the carbene adduct 32 was formed. By contrast, when 31 was reacted with the softer Lewis Acid BH3, it was the phosphorus that reacted to yield adduct 33. These types of carbenes exhibited C-NMR shifts in the range of 320-348 ppm, a P-C-N angle of 116.5° a short C-N distance of 1.296 A, and a long C-P distance of 1.856 A. The latter is very similar to that of a typical C-P single bond. 

Carbenes are defined as molecular species with formally divalent and two-coordinate carbon atoms bearing various substituents X and Y and a lone pair of electrons. While the simple representatives are of low stability (such as CH2) and may only appear as short-lived reaction intermediates or in adducts with electron donors, some cyclic systems can be readily isolated. This is particularly true for many of the A-heterocyclic carbenes (NHCs), which are now widely applied as ligands to metals ( Wanzlick-Arduengo carbenes ). Such carbenes based on imidazol and benzimidazol have become the working horses in this branch of organogold chemistry (Scheme 54). 

Cyclodditions to Carbonyl Derivatives. Electrophilic transient carbenes are known to react with carbonyl derivatives through the oxygen lone pair to give carbonyl ylides 26.43 These 1,3-dipolar species are usually characterized by [3 + 2]-cycloaddition reactions or can even be isolated44 a small amount of the corresponding oxiranes is sometimes obtained.433,45 To date, no reaction of transient nucleophilic carbenes with carbonyl derivatives has been reported. 

The reaction is predicted to be exothermic by 86 kcal/mol with an activation energy of 10 kcal/mol. The former is not unreasonable given that a lone pair (on the carbene) has been exchanged for a CC bond. The latter is in line with the observation that (singlet) carbene insertion reactions are known to be very fast. 

Because of the presence of a lone pair and a vacant orbital, singlet carbenes are supposed to be able to react with both Lewis bases and acids. Transient electrophilic carbenes are known to react with Lewis bases to give normal ylides (Scheme 8.19). For example, carbene-pyridine adducts have been spectroscopically characterized and used as a proof for the formation of carbenes,and the reaction of transient dihalogenocarbenes with phosphines is even a preparative method for C-dihalogeno phosphorus ylides. Little is known about the reactivity of transient carbenes with Lewis acids. 

Interestingly, highly regioselective reactions were also observed by addition of Lewis acids to the (amino)(phosphino)carbene (XVd). Indeed with one equivalent of BF3 OEt2 the quantitative formation of the carbene-BF3 complex was observed, whereas the softer Lewis acid BH3 interacts selectively with the phosphorus lone pair to afford a new stable carbene XVId (Scheme 8.25). ... 

A plausible reaction mechanism for this reaction was proposed by the authors. The Cu(i) carbene 182 generated from ethyl diazoacetate and the chiral Gu(i) complex can either react with another molecule of ethyl diazoacetate to form a mixture of diethyl maleate and fumarate 183, or with the imine lone pair to form a Gu(i)-complexed azomethine ylide... 

For a monograph, see Johnson Ylid Chemistry, Academic Press New York. 1966. For reviews, sec Morris. Surv. Prog. Chem. 1983, 10, 189-257 Hudson Chem. Br. 1971, 7, 287-294 Lowe Chem. Ind. (London) 1970, 1070-1079. For a review on the formation of ylides from the reaction of carbenes and carbenoids with heteroatom lone pairs, see Padwa Hornbuckle Chem. Rev. 1991, 91, 263-309. 

The reaction is assumed to involve initial formation of a carbene, by decomposition of the diazo compound with loss of nitrogen, followed by reaction of the electron-deficient carbene with the lone pair of electrons of the arsenic atom. Thermolysis of diazo compounds in copper-catalyzed reactions is known to provide singlet carbenes or carbenoid species (17). 

Another anomalous cycloaddition is the insertion of a carbene into an alkene. 6-Electron cheletropic reactions (p. 28) are straightforward allowed pericyclic reactions, which we can now classify with the drawings 3.47 for the suprafacial addition of sulfur dioxide to the diene 2.179 and its reverse. Similarly, we can draw 3.48 for the antarafacial addition of sulfur dioxide to the triene 2.180 and its reverse. The new feature here is that one of the orbitals is a lone pair, which is given the letter co to distinguish it from o- and n-bonds, with suprafacial and antarafacial defined by the drawings 3.45 and 3.46, which apply to all sp3 hybrids and p orbitals, filled or unfilled. 

Carbene attack is followed by proton transfer to generate a neutral molecule from the first formed zwitterion (or ylid ). However, if the heteroatom does not carry a hydrogen, attack on its lone pair generates an ylid that cannot rearrange in this way. Reaction of a carbene with a neutral nucleophile forms an ylid. This type of reaction is, in fact, a very useful way of making reactive ylids that are inaccessible by other means. 

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