Reactivity and selectivity in intermolecular insertion reactions of chlorophenylcarbene

Doyle, Michael P.; Taunton, Jack; Oon, Su Min; Liu, Michael T. H.; Soundararajan, Ν.; Platz, Matthew S.; Jackson, James E.

doi:10.1016/s0040-4039(00)82210-8

Cited by 36 publications

(15 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With few exceptions, , most singlet alkyl or alkylaryl carbenes undergo rapid intramolecular 1,2-hydrogen, alkyl, or aryl migrations to form alkenes − or react by other fast intermolecular proceses. − The intramolecular rearrangements have been the focus of extensive investigations, both experimental − ,,− and theoretical. ,,− …”

Section: Introductionmentioning

confidence: 99%

Dynamics of 1,2-Hydrogen Migration in Carbenes and Ring Expansion in Cyclopropylcarbenes

Albu¹,

Lynch²,

Truhlar³

et al. 2002

J. Phys. Chem. A

View full text Add to dashboard Cite

Variational transition state theory with multidimensional tunneling contributions has been used to calculate the rate constants, kinetic isotope effects, and activation energies for 1,2-shifts in methylchlorocarbene, benzylchlorocarbene, cyclopropylfluorocarbene, and cyclopropylchlorocarbene. Calculations have been performed for the rearrangements both in the gas phase and in various solvents. Including solvation effects reduces the calculated activation barrier for each of these reactions. The effects of quantum mechanical tunneling are computed to be significant for the 1,2-hydrogen migrations and to be bigger for hydrogen than for deuterium. Consequently, the deuterium kinetic isotope effects are predicted to be relatively large but to decrease with increasing temperature. In contrast, tunneling is not calculated to play a significant role in either of the halocyclopropylcarbene rearrangements, which both involve the 1,2-shift of a CH2 group. Thus, heavy-atom tunneling is apparently not responsible for the fact that the calculated activation parameters are very different from experiment for cyclopropylfluorocarbene, with the experimental activation enthalpy much smaller than the calculated one and the experimental activation entropy much more negative than the computed value. Possible causes for the large differences between the calculated and measured activation parameters are discussed.

show abstract

Section: Introductionmentioning

confidence: 99%

Dynamics of 1,2-Hydrogen Migration in Carbenes and Ring Expansion in Cyclopropylcarbenes

Albu¹,

Lynch²,

Truhlar³

et al. 2002

J. Phys. Chem. A

View full text Add to dashboard Cite

show abstract

“…Both singlet and triplet carbenes show insertion reactions, although the mechanisms are different. Intermolecular CH insertions were systematically studied in low-temperature organic glasses by Tomioka et al − and Platz et al − The conclusion of these and many other studies is that triplet carbenes at low temperature react via an abstraction recombination mechanism with radical pairs as intermediates. Typical activation barriers for CH insertions of triplet carbenes are several kcal/mol (for example, for the reaction of diphenylcarbene with toluene in the solid state a barrier of 6.9 kcal/mol was determined) .…”

Section: Introductionmentioning

confidence: 99%

Insertion of Difluorovinylidene into Hydrogen and Methane

Kötting

Sander

1999

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Insertion reactions of difluorovinylidene 1b into H2, CH4, and CD4 have been observed in argon matrixes at 20−40 K. These reactions are controlled by diffusion of trapped species rather than by activation barriers, indicating that the activation barriers are very small (<1 kcal/mol) or absent. In contrast, no insertion was observed into CF4 or C2H4. With C2H4, addition to the double bond to give (difluoromethylene)cyclopropane (5) is the only pathway. This was rationalized by ab initio (MP2/6-31G(d,p)) and DFT (B3LYP/6-311++G(d,p)) calculations, which predict activation barriers of essentially zero for the H2 and CH4 insertion, but 40 and 3 kcal/mol for the insertion into CF4 and C2H4, respectively.

show abstract

“…Aware of these limitations, we turned our attention to diazirines, which are the cyclic valence isomers of diazo compounds . Though similarly capable of serving as carbene precursors through extrusion of N 2 , diazirines are typically more stable, allowing isolation of carbene precursors lacking electron-withdrawing functionality. − The most commonly encountered diazirines are the trifluoromethyl derivatives, which are often applied as photoaffinity probes in biological applications. , However, importantly for our purposes, the corresponding α-chlorodiazirines ( 1 ) are much more easily prepared than their trifluoromethyl analogues via the single-step Graham oxidation of amidine precursors (Figure C). , Simple treatment with bleach directly affords a diverse range of chlorodiazirines (see the experimental Supporting Information (SI) for details). Indeed, hundreds of amidine precursors bearing diverse substitution patterns are commercially available, enabling the straightforward preparation of a library of reagents…”

mentioning

confidence: 99%

Carbon Atom Insertion into Pyrroles and Indoles Promoted by Chlorodiazirines

et al. 2021

View full text Add to dashboard Cite

Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores, respectively. By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, the traditional haloform-based protocol central to the parent Ciamician-Dennstedt rearrangement can be modified to directly afford 3-(hetero)arylpyridines and quinolines. Chlorodiazirines are conveniently prepared in a single step by oxidation of commercially available amidinium salts. Selectivity as a function of pyrrole substitution pattern was examined, and a predictive model based on steric effects is put forward, with DFT calculations supporting a selectivity-determining cyclopropanation step. Computations surprisingly indicate that the stereochemistry of cyclopropanation is of little consequence to the subsequent electrocyclic ring opening that forges the pyridine core, due to a compensatory homoaromatic stabilization that counterbalances orbital-controlled torquoselectivity effects. The utility of this skeletal transform is further demonstrated through the preparation of quinolinophanes and the skeletal editing of pharmaceutically relevant pyrroles.

show abstract

Reactivity and selectivity in intermolecular insertion reactions of chlorophenylcarbene

Cited by 36 publications

References 12 publications

Dynamics of 1,2-Hydrogen Migration in Carbenes and Ring Expansion in Cyclopropylcarbenes

Dynamics of 1,2-Hydrogen Migration in Carbenes and Ring Expansion in Cyclopropylcarbenes

Insertion of Difluorovinylidene into Hydrogen and Methane

Carbon Atom Insertion into Pyrroles and Indoles Promoted by Chlorodiazirines

Contact Info

Product

Resources

About