Reports: AC4
47273-AC4 Reactive Organic Intermediates from Diazirines
This report covers four (reported) publications which appeared in 2008 and 2009 (through August 2009).
1. Enthalpy versus Entropy in Chlorocarbene/Alkene Addition Reactions.
Dichlorocarbene (CCl2) and Chlorofluorocarbene (CClF) were generated by the nanosecond laser flash photoysis (LFP) of dichlorodiazirine and chlorofluorodiazirine, respectively. We measured the rate constants and activation parameters for the additions of CCl2 and CClF to simple alkenes. We were thus able to demonstrate the existance of enthalpic barriers for CCl2 additions to cyclohexene and 1-hexene. With these two alkenes, the additions of the previously studied phenylchlorocarbene (PhCCl) are dominated by entropic contributions to the free energy of activation (ΔG*). However, additions of CCl2 display comparable contributions of enthalpy (ΔΗ*) and entropy (ΔS*) of activation to ΔG*, while CClF additions feature dominant enthalpic contributions to ΔG*. Entropic contributions, however, control the additions of all three carbenes to the highly reactive alkene, tetramethylethylene. Computational studies of these reactions are also described, but the calculated values of ΔΗ* and ΔS* agree rather poorly with the experimental values.
Moss, R.A.; Wang,L.; Zhang, M.; Skalit, C.; Krogh-Jespersen, K. J. Am. Chem. Soc. 2008, 130, 5634-5635.
2. Activation Parameters for Additions of Ambiphilic Methoxychlorocarbene to Alkenes.
Methoxychlorocarbene (MeOCCl) was generated by nanosecond LFP of methoxychlorodiazirine and added to tetramethylethylene (TME), acrylonitrile, methyl acrylate, and α-chloroacrylonitrile. The rate constants and activation parameters were determined for these addition reactions. The activation energies (in kcal/mol) were: chloroacrylonitrile (3.9), acrylonitrile (6.4), TME (5.8), and methyl acrylate (7.0). MeOCCl is the first carbene to exhibit appreciable activation energy in addition to TME, a reactive and nucleophilic alkene. However, this addition reaction is still dominated by the entropy of activation. Thus the contribution of the -TΔS* term to the free energy of activation (12.4 kcal/mol) is 7.2 kcal/mol, and is larger than ΔΗ* (5.2 kcal/mol). The measured activation energies also reflect the ambiphilicity of MeOCCl. Thus, Ea is lowest for the addition of the carbene to the highly electrophilic chloroacrylonitrile (3.9 kcal/mol), an alkene known to be an exceptional substrate for ambiphilic and nucleophilic carbenes. The experimental free energies of activation for MeOCCl are in accord with the observed alkene reactivities at ambient temperature: chloroacrylonitrile > acrylonitrile > methyl acrylate > TME. Considering the relative contributions of TΔS* and ΔΗ* to ΔG*, MeOCCl addition to methyl acrylate is marginally controlled by enthalpy, its addition to acrylonitrile displays comparable enthalpic and entropic components, while its additions to chloroacrylonitrile and TME are dominated by entropy.
Moss, R.A.; Zhang, M. Organic Lett. 2008, 10, 4045-4048.
3. A New Synthesis of Difluorodiazirine and the Absolute Reactivity of Difluorocarbene.
Difluorodiazirine was generated by the reaction of 2,4-dinitrophenoxyfluoro-diazirine with lithium fluoride and 15-crown-5 in HMPA. LFP of difluorodiazirine afforded difluorocarbene (CF2), which was added to TME, trimethylethylene, cyclohexene, and 1-hexene. The rate constants were measured for additions to these alkenes and compared to those determined previously for additions of CCl2 and CClF. Also, activation parameters were measured for additions of CF2 to TME and cyclohexene. Some anticipated trends for these electrophilic dihalocarbene additions were well expressed: Ea with either alkene increases in the order of increasing carbene stability, CCl2 < CClF < CF2, and Ea is greater for carbene additions to cyclohexene than TME. With regard to the ΔΗ*/ΔS* balance for additions to TME, CCl2 and CClF are entropy-dominated, while enthalpy and entropy are roughly comparable for CF2. With cyclohexene, enthalpy and entropy are roughly comparable for CCl2, but enthalpy dominates for CClF and CF2 additions. An unexpected trend was the apparent increase of ΔS*, parallel to the increases of ΔΗ* or Ea in the order CCl2 < CClF < CF2. Ordinarily, one would expect ΔS* to decrease as the carbene’s stability increases and its addition reaction transition state becomes later and tighter. Computational studies are in progress aimed at understanding these unexpected results.
Moss, R.A.; Wang, L.; Krogh-Jespersen, K. J. Am. Chem. Soc. 2009, 131, 2128- 2130.
4. Latent Nucleophilicity of Dichlorocarbene.
Dichlorocarbene (CCl2) is generally regarded as an electrophilic carbene that preferentialy adds to electron-rich (nucleophilic) alkenes. However, a singlet carbene like CCl2 is inherently both an electrophile and a nucleophile. Its behavior in any addition to an alkene depends on whether the “electrophilic” carbene LUMO (p)/alkene HOMO (π) or the “nucleophilic” carbene HOMO (σ)/alkene LUMO (π*) orbital interaction dominates in the carbene/alkene cycloaddition transition state and governs the direction of charge transfer between the carbene and the alkene. We determined the rate constants and activation parameters for the additions of CCl2 to methyl acrylate, acrylonitrile, and α-chloroacrylonitrile. With alkylethylenes such as TME, trimethylethylene, cyclohexene, and 1-hexene, CCl2 behaves as an electrophile; rate constants decrease (and Ea increases) as electron-donating alkyl groups are removed from the alkenes. Rate constants also decrease as electron-withdrawing groups are imposed on the alkenes. However, a 16.5-fold increase in rate constant is observed upon passing from acrylonitrile to α-chloroacrylonitrile and is indicative of nucleophilic CCl2 addition to the latter substrate. Activation parameters indicate that the rate increase for the CCl2-chloroacrylonitrile addition is largely due to a reduction in Ea. Computational studies support the importance of nucleophilic character in CCl2 additions to both acrylonitrile and chloroacrylonitrile.
Moss, R.A.; Zhang, M.; Krogh-Jespersen, K. Organic Lett. 2009, 11, 1947-1950.
