Intermolecular reactions, singlet carbenes

Intermolecular Insertions. Singlet carbenes undergo insertion reactions with X H bonds such as O—H (alcohols), N—H (amines), Si H (silanes), and so on. The reactions with alcohols can be extremely fast. Here, however, we focus on the C H insertion reactions of singlet carbenes, in which carbon-carbon bonds are created. ... 

The mechanism for the addition of singlet carbenes to alcohols has been studied in some detail (Bethell et al, 1971 Kirmse et al, 1981). By and large, the evidence supports two routes. The first, more common, sequence features initial formation of an ylid. Under some circumstances this reaction is reversible (Zupancic et al., 1985 Liu and Subramanian, 1984 Warner and Chu, 1984). Next, proton transfer, either intramolecularly, which may be slowed by symmetry constraints, or by a pair of intermolecular protonation and deprotonation steps, gives the ether. These reactions are outlined in (7). 

Analysis of the product distributions arising from both sensitized and non-sensitized irradiation of 2-allyloxyphenyldiazo species (8) showed that the C—H insertion product and much of the cyclopropanation arise from the triplet carbene.16 For the singlet carbene, intermolecular 0—H insertion with methanol is about 50 tunes faster than intramolecular addition to the double bond, hi this system, intramolecular reactions and intersystem crossing of the triplet carbene proceed at similar rates, hi the closely related indanyl system (9), the smaller RCR angle stabilizes the singlet state relative to the triplet and the intramolecular reactivity is dominated by the singlet state.17... 

Condensed-phase carbenes will often react with the surrounding solvent medium, but they can also combine with other solute molecules. Indeed, these intermolecular reactions commonly occur at rates that are limited only by diffusion. Consequently, such carbenes are just short-lived intermediates. Nevertheless, arylhalocarbenes tend to have much longer lifetimes than typical alkylhalocarbenes, e.g., three orders of magnitude longer, because the latter also undergo rapid 1,2-H shift to form al-kenes.168,169 Indeed, the lifetime (t) of singlet carbene 64 (2max = 310 nm)170 in 2,2,4-trimethylpentane (isooctane) is reported to be ca. 3.6 ps, as determined via laser flash photolysis (LFP) of diazirine 63.171... 

These results are quite distinct from the chemistry of phenyl carbene (PC) [100]. The chemistry of PC in hydrocarbons is independent of initial singlet or triplet carbene generation. Equilibration of singlet and triplet PC is faster than their intermolecular reactions. 

At that time, it was not possible to measure any of the rate constants of Scheme 1 directly but in some cases it was possible to measure ratios of rate constants or to determine if spin equilibration was much faster or slower than intermolecular reactions. Organic chemists could then only dream of determining the absolute rate constants of Scheme 1. This would become possible around 1980 with the invention of laser flash photolysis with nanosecond (ns) time resolution. But successful application of this tool would require knowledge of the electronic spectra of singlet and triplet carbenes. Low temperature spectroscopy was enormously helpful in this regard. 

UV photolysis (Chapman et al., 1976 Chedekel et al., 1976) and vacuum pyrolysis (Mal tsev et al., 1980) of trimethylsilyldiazomethane [122]. The silene formation occurred as a result of fast isomerization of the primary reaction product, excited singlet trimethylsilylcarbene [123] (the ground state of this carbene is triplet). When the gas-phase reaction mixture was diluted with inert gas (helium) singlet-triplet conversion took place due to intermolecular collisions and loss of excitation. As a result the final products [124] of formal dimerization of the triplet carbene [123] were obtained. 

The transient ketocarbene is also able to effect both intramolecular and intermolecular H-abstraction. The fact that a triplet state of the carbene is often implicated follows from observations that sensitized photolyses frequently enhance the abstraction pathway. Abstraction and radical combination results in the formal insertion of the carbene into the C—H (or S—H, N—H, etc.) bond. Insertions may also occur into C—C, C—O, C—S, C—Hal, etc. bonds the mechanisms are often not known, but a singlet state of the ketocarbene is probably involved in many cases. Reactions at soft basic centers (e.g. —S or —Br ) generally proceed by the preliminary formation of an ylide. The multiplicity of the possible pathways is illustrated in Scheme 7, equation (14) (photolysis in dioxane affords only 27, 57% and 28, 43%), and Scheme 8. ... 

We expect that this is the case for singlet and triplet phenyl carbene as well. Intermolecular C—H bond insertion reactions of phenyl carbene are well known but are unknown for singlet phenyl nitrene at ambient temperature, presumably due to the rapid rate of the competitive ring expansion process which forms dehydroazepine. 

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