Formation of a phosphorus-phosphorus bond by successive one-electron reductions of a two-phosphinines-containing macrocycle: crystal structures, EPR, and DFT investigations.

Chemical and electrochemical reductions of the macrocycle 1 lead to the formation of a radical monoanion anion [1](*)(-) whose structure has been studied by EPR in liquid and frozen solutions. In accord with experimental (31)P hyperfine tensors, DFT calculations indicate that, in this species, the unpaired electron is mainly localized in a bonding sigma P-P orbital. Clearly, a one-electron bond (2.763 A) was formed between two phosphorus atoms which, in the neutral molecule, were 3.256 A apart (crystal structure). A subsequent reduction of this radical anion gives rise to the dianion [1](2)(-) which could be crystallized by using, in the presence of cryptand, Na naphthalenide as a reductant agent. As shown by the crystal structure, in [1](2)(-), the two phosphinine moieties adopt a phosphacyclohexadienyl structure and are linked by a P-P bond whose length (2.305(2) A) is only slightly longer than a usual P-P bond. When the phosphinine moieties are not incorporated in a macrocycle, no formation of any one-electron P-P bond is observed: thus, one-electron reduction of 3 with Na naphthalenide leads to the EPR spectrum of the ion pair [3](*)(-) Na(+); however, at high concentration, these ion pairs dimerize, and, as shown by the crystal structure of [(3)(2)](2)(-)[(Na(THF)(2))(2)](2+) a P-P bond is formed (2.286(2) A) between two phosphinine rings which adopt a boat-type conformation, the whole edifice being stabilized by two carbon-sodium-phosphorus bridges.     

EPR and DFT studies of the one-electron reduction product of phospholium cations

Cyclic voltammetry and EPR spectroscopy show that cationic phospholium groups are good electron acceptors whose reduction leads to a neutral radical where the unpaired electron is mainly delocalized on the carbon atoms of the five-membered ring. DFT calculations together with the crystal structure of phospholiums indicate that the electron addition causes a drastic diminution of the exocyclic CPC angle. The SOMO of reduced phospholium is compared to the SOMO of the phosphole radical anion.     

Evidence for Extensive Single‐Electron‐Transfer Chemistry in Boryl Anions: Isolation and Reactivity of a Neutral Borole Radical

Despite the synthesis of a boryl anion by Yamashita et al. in 2006, compounds that show boron‐centered nucleophilicity are still rare and sought‐after synthetic goals. A number of such boryl anions have since been prepared, two of which were reported to react with methyl iodide in apparent nucleophilic substitution reactions. One of these, a borolyl anion based on the borole framework, has now been found to display single‐electron‐transfer (SET) reactivity in its reaction with triorganotetrel halides, which was confirmed by the isolation of the first neutral borole‐based radical. The radical was characterized by elemental analysis, single‐crystal X‐ray crystallography, and EPR spectroscopy, and has implications for the understanding of boron‐based nucleophilic behavior and the emergent role of boron radicals in synthesis. This radical reactivity was also exploited in the synthesis of compounds with rare B? Sn and B? Pb bonds, the latter of which was the first isolated and structurally characterized compound with a “noncluster” B? Pb bond.     

Heat of hydrogenation of 1,5-dehydroquadricyclane. A computational and experimental study of a highly pyramidalized alkene

The radical anion of the highly pyramidalized alkene 1,5-dehydroquadricyclane (1) was generated in the gas phase from the Squires reaction of 1,5-bis(trimethylsilyl)quadricyclane with F-/F2. The electron binding energy and proton affinity of 1*- were determined by bracketing experiments to be 0.6 +/- 0.1 eV and 386 +/- 5 kcal/mol, respectively. These values are in good agreement with values predicted by density functional theory (B3LYP/6-31+G*) and ab initio (CASPT2/6-31+G*) calculations. The experimental heat of hydrogenation of 1, obtained from a thermochemical cycle, was found to be 91 +/- 9 kcal/mol. This value of deltaH(H2) leads to values of 67 +/- 9 kcal/mol for the olefin strain energy (OSE) of 1, 172 +/- 9 kcal/mol for its heat of formation, and 23 +/- 9 kcal/mol for its pi bond dissociation enthalpy. Since the retro-Diels-Alder reaction of neutral 1 is computed to be highly exothermic, the finding that 1*- apparently does not undergo a retro-Diels-Alder reaction is of particular interest. The B3LYP/6-31+G* optimized geometry of 1 suggests that the bonding in this alkene is partially delocalized, presumably because the highly pyramidalized double bond in 1 interacts with the distal cyclopropane bonds in a manner that eventually leads to a retro-Diels-Alder reaction. The good agreement of the B3LYP and (2/2)CASPT2 values for the heat of hydrogenation and OSE of 1 with the experimentally derived values provides indirect evidence for the correctness of the B3LYP prediction that the equilibrium geometry of 1 lies part way along the reaction coordinate to the transition structure for the retro-Diels-Alder reaction.     

Design of Leaving Groups in Radical CC Fragmentations: Through‐Bond 2c–3e Interactions in Self‐Terminating Radical Cascades

Radical cascades terminated by β‐scission of exocyclic C?C bonds allow for the formation of aromatic products. Whereas β‐scission is common for weaker bonds, achieving this reactivity for carbon–carbon bonds requires careful design of radical leaving groups. It has now been found that the energetic penalty for breaking a strong σ‐bond can be compensated by the gain of aromaticity in the product and by the stabilizing two‐center, three‐electron “half‐bond” present in the radical fragment. Furthermore, through‐bond communication of a radical and a lone pair accelerates the fragmentation by selectively stabilizing the transition state. The stereoelectronic design of radical leaving groups leads to a new, convenient route to Sn‐functionalized aromatics.     

Intramolecular electron transfer in cofacially pi-stacked fluorenes: evidence of tunneling

The one-electron reduction of neutral pi-stacked di- and trifluorenes (F-2 and F-3) in HMPA, where ion association is absent, results in the formation of anion radicals in which the odd electron resides predominantly on just one of the external fluorene moieties, as established by EPR spectroscopy. However, in the case of tetrafluorene, introduction of a single electron leads to a kinetically controlled anion radical F-4(int)*- in which the odd electron undergoes rapid exchange between two central fluorene rings, where the anionic charge is partially shielded from solvation due to the presence of external fluorene rings. On a time scale of minutes, anion radical F-4(int)*- converts to a thermodynamically stabilized anion radical F-4(ext)*-, with the electron exhibiting coupling from the protons on an external fluorene moiety. The charge and spin residing on an external moiety allow efficient solvation of the anionic charge. A similar fast exchange of a single electron (probably with the involvement of quantum mechanical tunneling) among three and four internal fluorene moieties is initially observed via EPR spectroscopy in the penta- and hexafluorene derivatives, F-5 and F-6, respectively.     

Making Aromatic Phosphorus Heterocycles More Basic and Nucleophilic: Synthesis,Characterization and Reactivity of the First Phosphinine Selenide

The synthesis and isolation of a phosphinine selenide was achieved for the first time by reacting red selenium with 2,6-bis(trimethylsilyl)phosphinine. The rather large coupling constant of ¹J_P,Se=883 Hz is in line with a P−Se bond of high s-character. The σ-electron donating Me₃Si-substituents significantly increase the energy of the phosphorus lone pair and hence its basicity, making the heterocycle considerably more basic and nucleophilic than the unsubstituted phosphinine C₅H₅P, as confirmed by the calculated gas phase basicities. NBO calculations further reveal that the lone pairs of the selenium atom are stabilized through donor-acceptor interactions with antibonding orbitals of the aromatic ring. The novel phosphinine selenide shows a distinct reactivity towards hexafluoro-2-butyne, Au(I)Cl as well as ⁱPrOH. Our results pave the way for new perspectives in the chemistry of phosphorus in low coordination.     

Tunneling and sterically induced ring puckering in a substituted [8]annulene anion radical

Electron paramagnetic resonance (EPR) studies have revealed that the steric interaction between the methyl hydrogens on a tert-butoxy substituent and the cyclooctatetraene (COT) ring system sterically induces a puckering of the eight-membered ring in the anion radical of tert-butoxy-COT. The induced nonplanarity of the COT ring system causes a large attenuation of the EPR coupling constants. Since the C-D bond length is slightly shorter than is the C-H bond length, replacement of the tert-butyl group with a tert-butyl-d(9) group results in less steric interaction and measurably larger electron proton coupling constants. The oscillation between the two close to planar alternating bond length (ABL) D(2d) conformers of the COT moiety was found to be extremely rapid (k > 10(12) s(-1)) and quantum mechanical tunneling is proposed to be involved.     

3‐Bromo‐2‐Pyrone: An Alternative and Convenient Route to Functionalized Phosphinines

The facile access to 3‐bromo‐2‐pyrone allows the preparation of 6‐bromo‐2‐trimethylsilyl‐phosphinine by a [4+2] cycloaddition with Me₃Si‐C≡P for the first time. The regioselectivity of this reaction could be verified by means of single crystal X‐ray diffraction of the corresponding W⁰ complex. In the presence of ZnBr₂ and dppp (1,3‐bis(diphenylphosphino)propane) as a bidentate ligand, the bromo‐phosphinine quantitatively undergoes a Negishi cross‐coupling reaction with PhLi that selectively leads to 6‐phenyl‐2‐trimethylsilyl‐phosphinine. This heterocycle could again be characterized by means of X‐ray diffraction as a W⁰ complex. These results describe a new and convenient route to 2,6‐disubstituted phosphinines that makes use of readily available starting materials.     

Theoretical study on structures and aromaticities of P5(-) anion, [Ti (eta(5)-P5)]- and sandwich complex [Ti(eta(5)-P5)2]2-

The equilibrium geometries, energies, harmonic vibrational frequencies, and nucleus independent chemical shifts (NICSs) of the ground state of P5(-) (D(5h)) anion, the [Ti (eta(5)-P5)]- fragment (C(5v)), and the sandwich complex [Ti(eta(5)-P5)2]2- (D(5h) and D(5d)) are calculated by the three-parameter fit of the exchange-correlation potential suggested by Becke in conjunction with the LYP exchange potential (B3LYP) with basis sets 6-311+G(2d) (for P) and 6-311+G(2df) (for Ti). In each of the three molecules, the P-P and Ti-P bond distances are perfectly equal: five P atoms in block P5(-) lie in the same plane; the P-P bond distance increases and the Ti-P bond distance decreases with the order P5(-), [Ti(eta(5)-P5)2]2-, and [Ti (eta(5)-P5)]-. The binding energy analysis, which is carried out according to the energy change of hypothetic reactions of the three species, predicts that the three species are all very stable, and [Ti (eta(5)-P5)]- (C(5v)), more stable than P5(-) and [Ti(eta(5)-P5)2]2- synthesized in the experiment, could be synthesized. NICS values, computed for the anion and moiety of the three species with GIAO-B3LYP, reveal that the three species all have a larger aromaticity, and NICS (0) of moiety, NICS (1) of moiety, and minimum NICS of the inner side of ring P5 plane in magnitude increase with the order P5(-), [Ti(eta(5)-P5)2]2-, and [Ti (eta(5)-P5)]-. By analysis of the binding energetic and the molecular orbital (MO) and qualitative MO correlation diagram, and the dissection of total NICS, dissected as NICS contributions of various bonds, it is the main reason for P5(-) (D(5h)) having the larger aromaticity that the P-P sigma bonds, and pi bonds have the larger diatropic ring currents in which NICS contribution are negative, especially the P-P sigma bond. However, in [Ti (eta(5)-P5)]- (C(5v)) and [Ti(eta(5)-P5)2]2- (D(5h), and D(5d)), the reason is the larger and more negative diatropic ring currents in which the NICS contributions of P-P pi bonds and P5-Ti bonds including pi, delta, and sigma bonds, especially P5-Ti bonds, are much more negative and canceled the NICS contributions of P and Ti core and lone pair electrons.     

The isolable cation radical of disilene: synthesis, characterization, and a reversible one-electron redox system

The highly twisted tetrakis(di-tert-butylmethylsilyl)disilene 1 was treated with Ph3C+.BAr4- (BAr4-: TPFPB = tetrakis(pentafluorophenyl)borate) in toluene, producing disilene cation radical 3 upon one-electron oxidation. Cation radical 3 was isolated in the form of its borate salt as extremely air- and moisture-sensitive red-brown crystals. The molecular structure of 3 was established by X-ray crystallography, which showed a highly twisted structure (twisting angle of 64.9 degrees) along the central Si-Si bond with a bond length of 2.307(2) A, which is 2.1% elongated relative to that of 1. The cation radical is stabilized by sigma-pi hyperconjugation by the four tBu2MeSi groups attached to the two central sp2-Si atoms. An electron paramagnetic resonance (EPR) study of the hyperfine coupling constants (hfcc) of the 29Si nuclei indicates delocalization of the spin over the central two Si atoms. A reversible one-electron redox system between disilene, cation radical, and anion radical is also reported.     

Kinetic and thermodynamic characterization of Co(II)-substrate radical pair formation in coenzyme B12-dependent ethanolamine ammonia-lyase in a cryosolvent system by using time-resolved, full-spectrum continuous-wave electron paramagnetic resonance spectroscopy

The formation of the Co(II)-substrate radical pair catalytic intermediate in coenzyme B12 (adenosylcobalamin)-dependent ethanolamine ammonia-lyase (EAL) from Salmonella typhimurium has been studied by using time-resolved continuous-wave electron paramagnetic resonance (EPR) spectroscopy in a cryosolvent system. The 41% v/v DMSO/water cryosolvent allows mixing of holoenzyme and substrate, (S)-2-aminopropanol, at 230 K under conditions of kinetic arrest. Temperature step from 230 to 234-248 K initiates the cleavage of the cobalt-carbon bond and the monoexponential rise (rate constant, k(obs) = tau(obs)(-1)) of the EPR-detected Co(II)-substrate radical pair state. The detection deadtime: tau(obs) ratio is reduced by >10(2), relative to millisecond rapid mixing experiments at ambient temperatures. The EPR spectrum acquisition time is 5tau(obs), the approximately 10(2)-fold slower rate of the substrate radical rearrangement reaction relative to k(obs), and the reversible temperature dependence of the amplitude indicate that the Co(II)-substrate radical pair and ternary complex are essentially at equilibrium. The reaction is thus treated as a relaxation to equilibrium by using a linear two-step, three-state mechanism. The intermediate state in this mechanism, the Co(II)-5'-deoxyadenosyl radical pair, is not detected by EPR at signal-to-noise ratios of 10(3), which indicates that the free energy of the Co(II)-5'-deoxyadenosyl radical pair state is >3.3 kcal/mol, relative to the Co(II)-substrate radical pair. Van't Hoff analysis yields DeltaH13 = 10.8 +/- 0.8 kcal/mol and DeltaS13 = 45 +/- 3 cal/mol/K for the transition from the ternary complex to the Co(II)-substrate radical pair state. The free energy difference, DeltaG13, is zero to within one standard deviation over the temperature range 234-248 K. The extrapolated value of DeltaG13 at 298 K is -2.6 +/- 1.2 kcal/mol. The estimated EAL protein-associated contribution to the free energy difference is DeltaG(EAL) = -24 kcal/mol at 240 K, and DeltaH(EAL) = -13 kcal/mol and DeltaS(EAL) = 38 cal/mol/K. The results show that the EAL protein makes both strong enthalpic and entropic contributions to overcome the large, unfavorable cobalt-carbon bond dissociation energy, which biases the reaction in the forward direction of Co-C bond cleavage and Co(II)-substrate radical pair formation.     

Sterically crowded bicyclo[1.1.0]butane radical cations

The variability of carbon-carbon single bonds by steric and electronic effects is probed by DFT calculations of sterically crowded bicyclo[1.1.0]butanes and their radical cations. The interplay of sterics and electronics on the gradual weakening and breaking of bonds was studied by investigating bridgehead substitution in 1,3-di-tert-butylbicyclo[1.1.0]butane and 2,2',4,4'-tetramethyl-1,3-di-tert-butylbicyclo[1.1.0]butane and geminal substitution in 2,2'-di-tert-butylbicyclo[1.1.0]butane and 2,2',4,4'-tetra-tert-butylbicyclo[1.1.0]butane. Bridgehead substitution leads to a lengthening of the central bond, whereas bisubstitution on the geminal carbon leads to a shortening of this bond due to a Thorpe-Ingold effect. Although the character of the central bond can be modulated by substitution and electron transfer over a range of 0.35 A, the state forbidden ring planarization does not occur. Sterically crowded bicyclo[1.1.0]butane radical cations are therefore promising candidates for the investigation of extremely long carbon-carbon single bonds.     

Dynamic study of photosensitized one-electron oxidation of polyG by menadione

Quinones including menadione are ubiquitous in nature. They play important roles in aerobic respira- tion and photosynthesis[1,2]. In addition, exogenous quinones are used as antibiotics and anticancer drugs. Their function is closely related to their red…     

Regioselective bond cleavage in the dissociative electron transfer to benzyl thiocyanates: the role of radical/ion pair formation

Important aspects of the electrochemical reduction of a series of substituted benzyl thiocyanates were investigated. A striking change in the reductive cleavage mechanism as a function of the substituent on the aryl ring of the benzyl thiocyanate was observed, and more importantly, a regioselective bond cleavage was encountered. A reductive alpha-cleavage (CH(2)-S bond) was seen for cyano and nitro-substituted benzyl thiocyanates leading to the formation of the corresponding nitro-substituted dibenzyls. With other substituents (CH(3)O, CH(3), H, Cl, and F), both the alpha (CH(2)-S) and the beta (S-CN) bonds could be cleaved as a result of an electrochemical reduction leading to the formation of the corresponding substituted monosulfides, disulfides, and toluenes. These final products are generated through either a protonation or a nucleophilic reaction of the two-electron reduction-produced anion on the parent molecule. The dissociative electron transfer theory and its extension to the formation/dissociation of radical anions, as well as its extension to the case of strong in-cage interactions between the produced fragments ("sticky" dissociative electron transfer (ET)), along with the theoretical calculation results helped rationalize (i) the observed change in the ET mechanism, (ii) the dissociation of the radical anion intermediates formed during the electrochemical reduction of the nitro-substituted benzyl thiocyanates, and more importantly (iii) the regioselective reductive bond cleavage.     

Sulfur radical cation-peptide bond complex in the one-electron oxidation of S-methylglutathione

Neighboring group participation was investigated in the *OH-induced oxidation of S-methylglutathione in aqueous solutions. Nanosecond pulse radiolysis was used to obtain the spectra of the reaction intermediates and their kinetics. Depending on the pH, and the concentration of S-methylglutathione, pulse irradiation leads to different transients. The transients observed were an intramolecularly bonded [>S thereforeNH2]+ intermediate, intermolecularly S thereforeS-bonded radical cation, alpha-(alkylthio)alkyl radicals, alpha-amino-alkyl-type radical, and an intramolecularly (S thereforeO)+-bonded intermediate. The latter radical is of particular note in that it supports recent observations of sulfur radical cations complexed with the oxygen atoms of peptide bonds and thus has biological and medical implications. This (S thereforeO)+-bonded intermediate had an absorption maximum at 390 nm, and we estimated its formation rate to be >or=6x10(7) s(-1). It is in equilibrium with the intermolecularly S thereforeS-bonded radical cation, and they decay together on the time scale of a few hundred microseconds. The S thereforeS-bonded radical cation is formed from the monomeric sulfur radical cation (>S*+) and an unoxidized S-methylglutathione molecule with the rate constant of 1.0x10(9) M(-1) s(-1). The short-lived [>S thereforeNH2]+ intermediate is a precursor of decarboxylation, absorbs at approximately 390 nm, and decays on the time scale of hundreds of nanoseconds. Additional insight into the details of the association of sulfur radical cations with the oxygen atoms of the peptide bonds was gained by comparing the behavior of the S-methylglutathione (S thereforeO+-bonded five-membered ring) with the peptide gamma-Glu-Met-Gly (S thereforeO+-bonded six-membered ring). Conclusions from experimental observations were supported by molecular modeling calculations.     

Enolates de l'acetylacetate d'ethyle. Structure et reactivite du sel de potassium en presence d'ether couronne et de cryptand

It is shown that, through the addition of 18-crown-6 or cryptand (2.2.2) to potassium ethyl acetoacetate enolate solutions in tetrahydrofuran, 1:1 complexes are formed. A single crystal of the 1:1 potassium énolate-18-crown-6 complex has been obtained. Its structure has been determined by X-ray diffraction. The crystal includes entities formed from an enolate anion chelating a potassium cation externally complexed by the crown-ether. The vibrational spectrometry shows that the structure of the entity is kept in solution. In the species formed through the addition of cryptand (2.2.2), the enolate anion has a structure (IR spectroscopy) and a reactivity very close to that of the free anion, observed in a dissociating solvent (DMSO, HMPA). When crown ether is added, a contact ion pair is formed, in which the cation is externally solvated by the crown. On the other hand, the cation encapsulation by the cryptand leads to a released anion with an “ S-trans” or “W” structure. The reactivity and the orientation of the alkylation reactions of these entities have been measured in THF solutions. They are discussed in relation to the structure of the species present in the reaction medium.     

New insight into the electronic structure of iron(IV)‐oxo porphyrin compound I. A quantum chemical topological analysis

The electronic structure of iron‐oxo porphyrin π‐cation radical complex Por^·+Fe^IV?O (S? H) has been studied for doublet and quartet electronic states by means of two methods of the quantum chemical topology analysis: electron localization function (ELF) η(r) and electron density ρ(r). The formation of this complex leads to essential perturbation of the topological structure of the carbon–carbon bonds in porphyrin moiety. The double C?C bonds in the pyrrole anion subunits, represented by pair of bonding disynaptic basins V_i=1,2(C,C) in isolated porphyrin, are replaced by single attractor V(C,C)_i=1–20 after complexation with the Fe cation. The iron–nitrogen bonds are covalent dative bonds, N→Fe, described by the disynaptic bonding basins V(Fe,N)_i=1–4, where electron density is almost formed by the lone pairs of the N atoms. The nature of the iron–oxygen bond predicted by the ELF topological analysis, shows a main contribution of the electrostatic interaction, Fe^δ+···O^δ?, as long as no attractors between the C(Fe) and C(O) core basins were found, although there are common surfaces between the iron and oxygen basines and coupling between iron and oxygen lone pairs, that could be interpreted as a charge‐shift bond. The Fe? S bond, characterized by the disynaptic bonding basin V(Fe,S), is partially a dative bond with the lone pair donated from sulfur atom. The change of electronic state from the doublet (M = 2) to quartet (M = 4) leads to reorganization of spin polarization, which is observed only for the porphyrin skeleton (?0.43e to 0.50e) and S? H bond (?0.55e to 0.52e). © 2012 Wiley Periodicals, Inc.     

Characterization of electron donor sites on Al2O3 surface

Formation of radical anions after adsorption of 1,3,5-trinitrobenzene (TNB) on electron donor sites of fully oxidized Al(2)O(3) samples with different phase compositions is studied by EPR. It is shown that the maximum concentration of the radical anions does not substantially depend on the choice of solvent and reaction temperature, and can be used to measure the total concentration of the donor sites. The donor sites are observed in almost the same concentration about 5 × 10(16) m(-2) on all alumina polymorphs except for α-Al(2)O(3). The formation rate of the TNB radical anions and the activation energy of this process are found to depend on the donor properties of the solvent. The EPR in situ experiments showed that a substantial amount of the adsorbate forming a liquid phase is required for generation of the radical anions. These results prove that the sites measured by the formation of the TNB radical anions are not genuine electron donor sites capable of direct electron transfer to the adsorbed TNB molecules. A model of the observed paramagnetic species based on the obtained experimental data and the results of quantum chemical simulations is suggested. According to this model, a TNB radical anion substitutes a hydroxyl group forming a neutral ion pair with a surface aluminum cation. The suggested mechanism for the formation of such ion pairs involves the migration of simple radicals and does not require long-distance charge separation. It is supposed that the donor site where the process is initiated includes a negatively charged surface hydroxyl group.     

Formation of a 1-bicyclo[1.1.1]pentyl anion and an experimental determination of the acidity and C-H bond dissociation energy of 3-tert-butylbicyclo[1.1.1]pentane

Decarboxylation of 1-bicyclo[1.1.1]pentanecarboxylate anion does not afford 1-bicyclo[1.1.1]pentyl anion as previously assumed. Instead, a ring-opening isomerization which ultimately leads to 1,4-pentadien-2-yl anion takes place. A 1-bicyclo[1.1.1]pentyl anion was prepared nevertheless via the fluoride-induced desilylation of 1-tert-butyl-3-(trimethylsilyl)bicyclo[1.1.1]pentane. The electron affinity of 3-tert-butyl-1-bicyclo[1.1.1]pentyl radical (14.8 plus minus 3.2 kcal/mol) was measured by bracketing, and the acidity of 1-tert-butylbicyclo[1.1.1]pentane (408.5 +/- 0.9) was determined by the DePuy kinetic method. These values are well-reproduced by G2 and G3 calculations and can be combined in a thermodynamic cycle to provide a bridgehead C-H bond dissociation energy (BDE) of 109.7 +/- 3.3 kcal/mol for 1-tert-butylbicyclo[1.1.1]pentane. This bond energy is the strongest tertiary C-H bond to be measured, is much larger than the corresponding bond in isobutane (96.5 +/- 0.4 kcal/mol), and is more typical of an alkene or aromatic compound. The large BDE can be explained in terms of hybridization.