From stable carbenes to stable Blatter-type radicals

Abstract

The overall theme of this project was investigation of the proton-transfer of stable carbene species. Stable carbenes, such as N-heterocyclic carbenes (NHCs) have recently been the focus of a great deal of research, due to their useful nature as organocatalysts for a wide range of synthetic transformations. As NHCs are typically generated in situ by deprotonation of their conjugate acids, the kinetics of protontransfer of NHCs and related species are highly important areas of research.
Using a kinetic method, the C(3)H acidity of a series of NHC conjugate acids, (imidazolium and triazolium based) was investigated at I = 1.0, 25 °C. The acidity was probed by H/D exchange experiments monitored by 1H NMR spectroscopy in D2O solutions at varied pD, from which the pseudo first-order rate constants of exchange kex (s−1) could be determined. Comparing the kex values at various pDs allows determination of the second-order rate constant of exchange kDO (M−1 s−1), for each azolium ion, and using a secondary solvent isotope effect (kDO/kHO = 2.4), estimates of pKa could be made by kinetic acidity, as the reprotonation of carbenes in water is known to be limited by solvent reorganisation (kHOH = kreorg = 1011 s−1).
pD rate profiles of ortho-halogen substituted triazolium salts studied by this method showed an altered dependence on pD at low pD, an effect which has previously been observed in an N-C6F5 triazolium salt. This effect is believed to originate from N1 protonation of the triazolium ring system under acidic conditions, to generate a dicationic triazolium species. Ortho-halogen substitution is believed to promote this effect by raising the pKa of the N1 position.
Two imidazolium salts with fused furan rings and exocyclic nitrogen atoms were also studied by this method and did not show altered dependence on pD. The carbon acidity C(3)H positions of these salts was significantly higher than is generally predicted for N-aryl imidazolium salts. The origin of this increased acidity is assigned to increased σ-electron withdrawal and π-donation by the O atom of the fused furan ring.
Bis(amino)cyclopropenylidenes (BACs) are a relatively new field of stable carbenes, and the only family with no α-heteroatoms to the carbene centre. Several BAC conjugate acids were prepared using existing literature procedures, however, attempts to prepare of N-aryl BACs by the use of N-methylaniline produced only trisubstituted cyclopropenium species. Hydrolysis of this to cyclopropenone, followed by
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chlorination and reaction with triphenylphosphine produced a phosphonium salt, instead of the desired BAC conjugate acid. Using diethylamine produced a mixture of disubstituted and trisubstituted cyclopropenium salts. The disubstituted product could not be purified after the use of triphenylphosphine. Replacement with triethyl phosphite afforded a stable phosphonato cyclopropenium salt. Base hydrolysis of the phosphonate yielded N-ethyl BAC conjugate acid, with competing elimination of ethanol.
The carbon acidity of the C(3)H position of two bis(amino)cyclopropenium salts was studied by the same kinetic acidity method used to investigate NHC conjugate acids. Control experiments determined a lack of buffer catalysis and confirmed H/D exchange had occurred. The lack of buffer catalysis suggests that as with NHCs, reprotonation of BACs is limited by solvent reorganisation (kHOH = kreorg = 1011 s−1). The determined values of kDO could be converted to kHO (kDO/kHO = 2.4), which in turn was used to estimate pKa (~22). This value is between the approximate acidity of N-aryl and N-alkyl imidazolium salts. Despite the lack of α-heteroatoms, the BAC is believed to be stabilised by a highly acute bond angle at the carbene centre and by σ-withdrawal and π-donation from the exocyclic nitrogen substituents.
The unusual hydrolytic behaviour of the phosphonato-cyclopropenium species was investigated. Further phosphonato-cyclopropenium salts were prepared by reaction of alkyl phosphites with chloro-cyclopropenium salts. Hydrolysis of these phosphonates largely favoured elimination of a BAC compared to ethoxide, contrary to what would be expected from the respective pKa values of the leaving groups. The kinetics of hydrolysis was investigated using 31P NMR spectroscopy at 25°C, I = 1.0 M in various K2CO3 buffers in H2O and D2O. A first-order dependence on hydroxide/deuteroxide was observed with no significant solvent kinetic isotope effect. Variable temperature experiments suggested an associative mechanism, and at varied temperature, ionic strength and basicity, identical ratios of products were produced. From this information, it is proposed that hydrolysis proceeds via either an AN+DN or SN2@P mechanism. The unusual ratio of products could be potentially be explained by rate-limiting pseudorotation during an AN+DN mechanism.
Investigation of the organocatalytic chemistry of BACs involved following the BACcatalysed intramolecular Stetter reaction by 1H NMR spectroscopy at 25 °C. The degree of steric hindrance around the BAC was of vital importance, as the reaction did not
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proceed using bulky catalysts. A similar 2-substituent effect of aryl aldehydes in reaction with NHCs was observed with BACs. Several hydroxy-aryl adducts of BACs were prepared and isolated, and the formation of a d1-acyl anion equivalent was investigated by H/D exchange experiments. Exchange was observed under organocatalytic conditions, and experiments monitored by 1H NMR in highly basic aqueous (D2O, I = 1.0, 25 °C) conditions found exchange to occur. The second-order rate constants of exchange kDO showed a moderate aryl substituent effect between adducts.
Finally, the serendipitous discovery of a “Blatter”-type radical formed from carbenoid species Nitron found by previous MChem student Jacob A. Grant was investigated. A further radical derivative compound was discovered and both were fully characterised. Further synthetic and spectroscopic experiments suggested a possible mechanism for the formation of these radicals. Both radicals’ properties were found to be largely similar to previous examples of “Blatter”-type radicals through cyclic voltammetry and EPR experiments.