Carbene selectivity

R. A. Moss, Carbenic Selectivity in Cyclopropanation Reactions, Acc. Chem. Res. 1980,... 

Table 40 Heterocyclic carbenes selected NMR chemical shifts (ppm)...

Collaboration has played a consistent role in his research. His first collaborative project was with Professor Bob Moss, who approached Houk about help in interpreting carbene selectivity. Houk recalls a collaboration with Professor A1 Meyers concerning a failed anionic amino-Cope rearrangement. He had this reaction that didn t work and we did some calculations to explain why, he remembers, and this appeared as a JACS communication. Then for some time afterwards, A1 and others would call to say Hey, I ve got this reaction that doesn t work Can we get a JACS conununication ... 

A thorough discussion on carbene selectivities in their addition to alkenes is reported in ref 19. 

Muller chose to examine cyclohexene and 1,4-cyclohexadiene (ten equivalents relative to diazo compound) as model systems, and screened a variety of carbenoid precursors and catalysts (Scheme 24, left). All reactions were conducted in DCM at 25 °C. The results with 1,4-cyclohexadiene were quite clear-cut. With acceptor-substituted carbenes, selectivity was >95 5 in favor of cyclopropanation 108 for Cu° or Rh2(OAc)4 catalysts. For acceptor/acceptor carbenoid precursors, CuCl still favored cyclopropanation >95 5, but with Rh2(OAc)4 insertion 109 now became... 

To further characterize the selectivity of carbene CXY, we can compare its discrimination between the olefins of the standard set with that of CCI2, which we designate the standard carbene. We plot the logarithms of the relative reactivities for CXY against analogous data for CCI2 (with the relative reactivities all adjusted to the standard alkene, isobutene, = 1.00), and then determine the slope of the correlation line, Wcxy- We call m xy the carbene selectivity index, defined as the least-squares slope of log (V o)cxy s. log (kJk QQX. [8,9,16,17] The m xv values for the carbenes of Table 1, determined in this manner, are m p = 1.48 mcci, 1-00 (by definition), and m Br, 0-65. 

Similar numerical measures of of carbene/alkene discrimination had been previously obtained, [4,18,19] but we collected our OTcxy data at a single temperature (25 °C), only in hydrocarbon solvents, and generated the carbenes by methods likely to yield free, uncomplexed carbenes (rather than carbenoids [7,20]). Our data was therefore mutually comparable, and we were thus able to take another step in the quantitation of carbenic selectivity. 

Eq. 4 enabled an empirical analysis of carbenic selectivity (or philicity). (1) It correlated the selectivities of many of the carbenes that had been studied up to 1976. [8,17] (2) It quantitated the qualitative concepts of carbene-aUcene addition reactions that were prevalent. (3) Most importantly, it could be used to estimate the selectivity of new carbenes. (4) It led to the identification of ambi-philic carbenes. (5) It would later be found to parallel conclusions drawn from ah intio electronic structure calculations of carbene-alkene addition reactions. Eet s examine features (1) - (4) ah initio calculational results will be considered below, in Section 2.1. 

It was clear that we needed a better theoretical Iramework to parallel and permit interpretation of carbenic philicity. Two crucial developments occurred around 1980 the application of ab initio computational methods and frontier molecular orbital (FMO) theory to carbene/alkene addition reactions, and the measurement of absolute rate constants for these reactions by laser flash photolysis (LFP). Together, these approaches greatly clarified our understanding of carbenic selectivity and philicity, and defined the current state of the art. ... 

Flowever, PhCOMe has m icalcd) = 1.34. According to our empirical analysis of carbenic selectivity (Section 1.2), it should be an electrophile because its WcxY selectivity index lies between 0.29 and 1.48. What s wrong FMO... 

R. A. Moss, Carbenic philicity, in Carbene Chemistry From Fleeting Intermediates to Powerful Reagents, G. Bertrand (Ed.), Fontis Media-Marcel Dekker, Lausanne, 57—90, 2002 b) R. A. Moss, Carbenic selectivity in cyclopropanation reactions, Acc. Chem. Res., 1980, 13, 58-64 c) R. A. Moss, Carbenic reactivity revisited, Acc. Chem. Res., 1989, 22, 15-21. 

The addition of dimethoxycarbene to olefin, only a recently discovered reaction, has been subjected to detailed mechanistic study and the reaction stereochemistry has been unequivocally determined with the aid of labelled substrates. Thermally generated dimethoxycarbene undergoes stereospecific addition to P-deuteriostyrenes with no observable isotope effect for carbene selectivity between labelled and unlabelled olefin. This behaviour is most compatible with the concerted addition of a... 

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