Carbene reactivity

Studies have shown that carbene reactivity toward a wide variety of substrates is dramatically affected by the nature and multiplicity of the electronic state. - Similarly, the structure, electronic state, thermochemical stability, and reaction kinetics of both singlet and triplet carbenes can be significantly affected by the R-substituents. If R provides steric hindrance, the carbene center can be shielded to slow down inter-molecular reactions (kinetic stabilization). Additionally, bulky and/or geometrically... 

Carbene reactivity is strongly affected by substituents.117 Various singlet carbenes have been characterized as nucleophilic, ambiphilic, and electrophilic as shown in Table 10.2 This classification is based on relative reactivity toward a series of both nucleophilic alkenes, such as tetramethylethylene, and electrophilic ones, such as acrylonitrile. The principal structural feature that determines the reactivity of the carbene is the ability of the substituent to act as an electron donor. For example, dimethoxycarbene is devoid of electrophilicity toward alkenes because of electron donation by the methoxy groups.118... 

An HSAB analysis of singlet carbene reactivity based on B3LYP/6-31G computations has calculated the extent of charge transfer for substituted alkenes,122 and the results are summarized in Figure 10.3 The trends are as anticipated for changes in structure of both the carbene and alkene. The charge transfer interactions are consistent with HOMO-LUMO interactions between the carbene and alkene. Similarly, a correlation was found for the global electrophilicity parameter, co, and the ANmax parameters (see Topic 1.5, Part A for definition of these DFT-based parameters).123... 

Transition metals have been used to trap and stabilize many different types of reactive intermediates, such as carbenes. Reactive silicon intermediates have only recently yielded to this approach. In the case of alkenes, for instance, transition metal complexes are generally made by exposing the alkene to a transition metal bearing suitable leaving groups (e.g., carbonyl). Unlike carbon-based intermediates, however, silicon-based analogs have been very difficult to prepare until recently. Unless... 

Indeed, such donation is calculated to stabilize singlet dimethoxycarbene by 76 kcal/mol relative to the corresponding triplet.93 The electron donation also modulates carbenic reactivity 78 a strong electron donor on Q raises both the carbene s HOMO and LUMO energies, thereby increasing the carbene s nucle-ophilicity while rendering its LUMO less accessible to nucleophiles (decreasing its electrophilicity).94 These consequences are illustrated by 69 and the related structures in Scheme 6. 

Not much is known about the reactivity of the phosphinocarbene 2i. Problems arise, at least in part, from the high 1,3-dipolar reactivity of the diazo precursor li, which hides any carbene reactivity. Indeed, although li is stable in a toluene solution at 60°C for hours, the addition of an electron-poor olefin, such as a perfluoroalkyl-monosubstituted alkene, induces the exclusive formation of the thermodynamically more stable anti-isomer of the cyclopropane 14 (see Section V,B,3,a).36 This clearly demonstrates that the cyclopropanation reaction does not involve the carbene 2i, but that an initial [2 + 3]-cycloaddition occurs leading to the pyrazoline 13, which subsequently undergoes a classical N2 elimination.37... 

CH3)2C=C(CH3)2 to 3.3 X 10 M-h- for the addition of CH3OCCI to trans-pentene. This million-fold variation testifies to the great modulating power of carbenic substituents on carbenic reactivity. 

Extreme cases were reactions of the least stabilized, most reactive carbene (Y = CF3, X = Br) with the more reactive alkene (CH3)2C=C(CH3)2, and the most stabilized, least reactive carbene (Y = CH3O, X = F) with the less reactive alkene (1-hexene). The rate constants, as measured by LFP, were 1.7 x 10 and 5.0 X lO M s, respectively, spanning an interval of 34,000. In agreement with Houk s ideas,the reactions were entropy dominated (A5 —22 to —29e.u.). The AG barriers were 5.0 kcal/mol for the faster reaction and 11 kcal/ mol for the slower reaction, mainly because of entropic contributions the AH components were only —1.6 and +2.5 kcal/mol, respectively. Despite the dominance of entropy in these reactive carbene addition reactions, a kind of de facto enthalpic control operates. The entropies of activation are all very similar, so that in any comparison of the reactivities of alkene pairs (i.e., ferei)> the rate constant ratios reflect differences in AA//t, which ultimately appear in AAG. Thus, car-benic philicity, which is the pattern created by carbenic reactivity, behaves in accord with our qualitative ideas about structure-reactivity relations, as modulated by substiment effects in both the carbene and alkene partners of the addition reactions. " Finally, volumes of activation were measured for the additions of CgHsCCl to (CH3)2C=C(CH3)2 and frani-pentene in both methylcyclohexane and acetonitrile. The measured absolute rate constants increased with increasing pressure Ayf ranged from —10 to —18 cm /mol and were independent of solvent. These results were consistent with an early, and not very polar transition state for the addition reaction. 

Another broad class of compounds are the bridged carbene complexes. These compounds contain two identical or two different metal centers with the carbene centers bonded to both of the metal atoms in a bridging relationship. However, these binuclear complexes generally do not show classical carbene reactivity and will therefore not be discussed further, except to mention briefly the special case of the titanium-aluminum complex (3) developed by Tebbe and Grubbs and their coworkers.101 This, and related complexes, has proven to be particularly useful in organic synthesis, although its principal importance is in reactions other than cyclopropanations. 

The wealth of productive bond-forming processes that radiate from this one intermediate can make planning a synthesis route around alkynyliodonium/alkylidenecarbene chemistry a daunting prospect. The key to steering the alkylidenecarbene down a desired pathway involves exploiting proximity effects to juxtapose an appropriately reactive trap near the carbene terminus. These constraints in carbene reactivity... 

Although this view is oversimplified and borderline metal carbene complexes have been isolated, this approach is convenient for discussing the activity of metal carbene species in the ring-opening metathesis polymerisation of cycloolefins. Calculations have predicted [81,82] and recent results have shown [83] that, in some systems, metal alkylidene reactivity is competitive with metal carbene reactivity, i.e. olefin metathesis is competitive with olefin cyclopropanation. 

Kauer Zinn F, Viciu MS, Nolan SP (2004) Carbenes reactivity and catalysis. Annu Rep Prog Chem Sect B Org Che 100 231-249... 

New carbene complexes may arise from the modification of a preformed carbene ligand. Examples have already been met in the case of halocarbenes (Figure 5.10) however, further examples will be discussed under the topic of carbene reactivity. 

Despite the expected enhanced reactivity of trifluoromethyl-substituted carbenes as electrophilic species, yields in their [2+ l]-cycloaddition reactions with alkenes are highly dependent on the nature of the second substituent of the carbene. Furthermore, the method of carbene generation has a large influence on carbene reactivity. 

The relative rate of addition versus insertion can be used as a measure of carbene reactivity, too. For instance carbena-cyclopentadiene reacts with tetramethylethylene to give the spirocyclopropane 36 (A) and the alkenylcyclopentadiene 37 (I) A addition, I insertion. 

Carbenes reactive intermediates containing divalent carbon... 

Of the three classes of divalent carbon species—free carbenes, reactive transition-metal carbene complexes (carbenoids), and stable metal carbenes—we restrict our consideration to the first two. Taking into account the fact that a fine reaction mechanism in planning the synthesis of specific molecules is of secondary importance, we discuss carbene and carbenoid reactions together. We concentrate solely on reactions and reaction sequences that result in a formation of a new heterocycle. Within subsections, the material is organized on the basis of reaction type. 

Carbenic reactivity of transient 2-diazo-1,3-dithiane. Tetrahedron 1997, 53, 9269-9278. 

This type of Cj-extrusion reaction has been predominantly of theoretical interest, especially with respect to the correlation of carbene reactivity with the structure of the precursor and the method of cleavage/ However, some attempts to use this Cj-extrusion method to generate certain carbenes for synthetic uses have also been reported. Thus, hexamethoxycyclopropane (5) has been probed as a potential source of dimethoxycarbene (6). 

Wang, Y., Yuzawa, T., Hamaguchi, H., Toscano, J. R, Time resolved IR Sudies of 2 Naphthyl (carbomethoxy)carbene Reactivity and Direct Experimental Estimate of the Singlet/Triplet Energy Gap, J. Am. Chem. Soc. 1999, 212, 2875 2882. 

The effect of substituents on the temperature dependence of a-carbonyl-carbene reactivity has been examined using carbenes generated by low-temperature photolysis of methyl diazophenylacetate. A correction to the literature on the photoreaction of isopropylidene diazomalonate (98) with 1,3,3-trimethyl-cyclohexane (99) has been reported. The photoproduct, originally thought to be a cyclopropane derivative, has now been shown to be the cyclobutanone (100), the formation of which presumably involves a photo-Wolff rearrangement as illustrated in Scheme 11. Substituent effects observed in the product distribution of diazo-amide photochemistry have been ascribed to conformational factors the jS-lactam, oxindole, and Wolff rearrangement products appear to arise directly from the excited singlet state of the sym-Z form of the diazo-amide itself. 

During these last 10 years, the number of molecules identified in the interstellar medium has spectacularly increased. Most among the hrmdred of molecules now known have something in common their exotic character from the viewpoint of chemists. Whether they are radicals, carbenes, reactive ions, or metastable isomers of more common species, laboratory studies on such compounds usually remain problematic their reactivity is usually so high that they are either difficult to produce, or a least, difficult to keep alive for a long enough time to record their spectral signatures. 

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