Cyclopropylmethyl Radical Research Articles

Simple Synthesis of 1,2-Dideoxy-2-Vinyl Carbohydrates by Tin-Free Radical Reactions of Xanthates.

Vinyl-substituted carbohydrates have been synthesized from glycals derived from hexoses and pentoses. Key step is the radical reaction of xanthates in the presence of triethylborane, a non-toxic reagent. The mechanism has been investigated by isolation of various side products, which speak for a reversibility of the cyclopropylmethyl radical ring-opening. Compared to reactions with tributyltin hydride, higher regioselectivities in favor of the 2-vinyl-substituted sugars have been obtained. Yields are slightly lower with triethylborane, but all products have been isolated in analytically pure form. The new reaction is applicable to benzyl- and silyl-protected carbohydrates, which makes free sugars accessible as well. Overall, more than 15 1,2-dideoxy-2-vinyl carbohydrates have been synthesized from simple precursors in only few steps.

Structural and Electronic Noninnocence of α-Diimine Ligands on Niobium for Reductive C–Cl Bond Activation and Catalytic Radical Addition Reactions

A d0 niobium(V) complex, NbCl3(α-diimine) (1a), supported by a dianionic redox-active N,N'-bis(2,6-diisopropylphenyl)-1,4-diaza-2,3-dimethyl-1,3-butadiene (α-diimine) ligand (ene-diamido ligand) served as a catalyst for radical addition reactions of CCl4 to α-olefins and cyclic alkenes, selectively affording 1:1 radical addition products in a regioselective manner. During the catalytic reaction, the α-diimine ligand smoothly released and stored an electron to control the oxidation state of the niobium center by changing between an η4-(σ2,π) coordination mode with a folded MN2C2 metallacycle and a κ2-(N,N') coordination mode with a planar MN2C2 metallacycle. Kinetic studies of the catalytic reaction elucidated the reaction order in the catalytic cycle: the radical addition reaction rate obeyed first-order kinetics that were dependent on the concentrations of the catalyst, styrene, and CCl4, while a saturation effect was observed at a high CCl4 concentration. In the presence of excess amounts of styrene, styrene coordinated in an η2-olefinic manner to the niobium center to decrease the reaction rate. No observation of oligomers or polymers of styrene and high stereoselectivity for the radical addition reaction of CCl4 to cyclopentene suggested that the C-C bond formation proceeded inside the coordination sphere of niobium, which was in good accordance with the negative entropy value of the radical addition reaction. Furthermore, reaction of 1a with (bromomethyl)cyclopropane confirmed that both the C-Br bond activation and formation proceeded on the α-diimine-coordinated niobium center during transformation of the cyclopropylmethyl radical to a homoallyl radical. With regard to the reaction mechanism, we detected and isolated NbCl4(α-diimine) (6a) as a transient one-electron oxidized species of 1a during reductive cleavage of the C-X bonds; in addition, the monoanionic α-diimine ligand of 6a adopted a monoanionic canonical form with selective one-electron oxidation of the dianionic ene-diamido form of the ligand in 1a.

Mechanistic Study of SmI2‐Mediated Reformatsky Reaction for Macrolactam Formation Using a Cyclopropyl Group as a Probe

AbstractA mechanistic study using a cyclopropylmethyl radical clock as a probe to investigate the formation of a macrolactam ring via an SmI2‐mediated intramolecular Reformatsky reaction is experimentally explored. The results of our study indicate that the key SmIII‐enolate intermediate is formed by cleavage of a C−Br bond in an anion‐mediated β‐elimination, and then eventually undergoes an intramolecular aldol condensation to form the macrolactam ring.

A Radical Pathway for Direct Substitution of Benzyl Alcohols with Water‐Soluble Copper Catalyst in Water

AbstractWe have developed a novel strategy for the direct substitution of benzyl alcohols with anthranilic acids using water‐soluble copper catalysts through a radical pathway in water, which offers efficient and environmentally friendly N‐, S‐, and C‐benzylations under neutral conditions. Radical scavengers strongly inhibited the benzylation. Radical clock experiments using α‐cyclopropylbenzyl alcohol were conducted to observe the rapid isomerization of the cyclopropylmethyl radical to the allylmethyl radical. Hammett plots could be fitted to a two‐parameter Hammett relationship containing both radical and polar contributions [log (kX/kH)=−1.24 σ.–0.38 σ, R2=0.99]. The relative parameter ρ./ρ of 3.3 suggested that these reactions involved a strong radical character with minor polar influence at the transition state.magnified image

ChemInform Abstract: Radical Clocks as Probes of 1,4-Biradical Intermediates in the Photochemical Cycloaddition Reactions of 2-Cyclopentenone with Alkenes.

The products of the photochemical reaction of 2-cyclopentenone with 1,6-heptadiene and with vinylcyclopropane have been examined. With 1,6-heptadiene the products were cyclobutanes, which arise from 2 + 2 photocycloaddition between the cyclopentenone carbon–carbon double bond and one of the two terminal double bonds of the heptadiene. The 1,4-biradical that is an intermediate in this reaction contains a derivative of a 1-hexenyl radical; no products derived from cyclization of this intermediate to a cyclopentylmethyl radical were observed. With vinylcyclopropane some of the products isolated also arose from 2 + 2 photocycloaddition; in addition, comparable quantities of products resulting from rearrangement of the intermediate 1,4-biradical were obtained. In this case the initially produced intermediate 1,4-biradical contains a cyclopropylmethyl radical that can rearrange to a homoallylic radical; the products isolated were derived from intramolecular disproportionation in the new 1,7-biradical containing...

Theoretical prediction of the ionization energies of the C4H7 radicals: 1-Methylallyl, 2-methylallyl, cyclopropylmethyl, and cyclobutyl radicals

The ionization energies (IEs) for the 1-methylallyl, 2-methylallyl, cyclopropylmethyl, and cyclobutyl radicals have been calculated by the wave function based ab initio CCSD(T)/CBS approach, which involves the approximation to the complete basis set (CBS) limit at the coupled cluster level with single and double excitations plus quasiperturbative triple excitation [CCSD(T)]. The zero-point vibrational energy correction, the core-valence electronic correction, and the scalar relativistic effect correction are included in these calculations. The present CCSD(T)/CBS results are then compared with the IEs determined in the photoelectron experiment by Schultz et al. [J. Am. Chem. Soc. 106, 7336 (1984)] The predicted IE value (7.881 eV) of 2-methylallyl radical is found to compare very favorably with the experimental value of 7.90+/-0.02 eV. Two ionization transitions for cis-1-methylallyl and trans-1-methylallyl radicals have been considered here. The comparison between the predicted IE values and the previous measurements shows that the photoelectron peak observed by Schultz et al. likely corresponds to the adiabatic ionization transition for the trans-1-methylallyl radical to form trans-1-methylallyl cation. Although a precise IE value for the cyclopropylmethyl radical has not been directly determined, the experimental value deduced indirectly using other known energetic data is found to be in good accord with the present CCSD(T)/CBS prediction. We expect that the Franck-Condon factor for ionization transition of c-C4H7-->bicyclobutonium is much less favorable than that for ionization transition of c-C4H7-->planar-C4H7+, and the observed IE in the previous photoelectron experiment is likely due to the ionization transition for c-C4H7-->planar-C4H7+. Based on our CCSD(T)/CBS prediction, the ionization transition of c-C4H7-->bicyclobutonium with an IE value around 6.92 eV should be taken as the adiabatic ionization transition for the cyclobutyl radical. The present study provides support for the conclusion that the CCSD(T)/CBS approach with high-level energetic corrections can be used to provide reliable IE predictions for C4 hydrocarbon radicals with an uncertainty of +/-22 meV. The CCSD(T)/CBS predictions to the heats of formation for the aforementioned radicals and cations are also presented.

On the Mechanism of Cytochrome P450-Catalyzed Oxidations: Reaction of a New Enzyme Model with a Radical Clock

trans-2-Phenyl-methylcyclopropane was oxidized using PhIO and a P450 enzyme model carrying a SO3 - ligand coordinating to iron. Analysis of the product distribution revealed a ratio of 9:1 of the non-rearranged cyclopropyl methanol 18 over 1,1-allyl phenyl methanol 16. Given the rate of rearrangement k = 1.8·1011 sec-1 of the phenyl cyclopropyl methyl radical 14 in solution, the life time of the intermediate radical cluster I C-H can be calculated as 625 fsec. The hydroxylation proceeds by concerted non-synchronous ‘O’-insertion into the C-H bond of the methyl group.

A Tandem Radical Cyclization Route to Tricyclo[4.3.n.01,5]alkanes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A tandem radical cyclization route to tricyclo[4.3. n.0 1,5]alkanes

A facile route to tricyclo[4.3. n.0 1,5]alkane skeletons from conjugated cyclic enones was developed through tandem free radical cyclization reaction sequence involving the cyclopropylmethyl radical mediated rearrangement. The scope and limitation of the reaction was investigated.

Conformational Memory in Enantioselective Radical Reductions and a New Radical Clock Reaction

The radical decarboxylation of acid 1 led to tetrahydropyran 3 with significant optical activity. This transfer of chirality is an example of a conformational memory effect and derives from the slow ring inversion of the atropisomer 2 and its enantiomer 2‘. A similar conformational memory effect was observed in the reductive decyanation and reductive lithiation of cyanohydrin 4. We propose that the racemization of radicals with chiral conformations such as 2 could be used as new radical clocks. The rate of racemization of 2 was evaluated and used to determine the rate of H atom transfer to 2 by different H atom donors. The rate of racemization of 2 is 5.7 × 108 s-1 at 22 °C, which is about five times faster than ring opening of a cyclopropylmethyl radical.

Homolytic C−S Bond Scission in the Desulfurization of Aromatic and Aliphatic Thiols Mediated by a Mo/Co/S Cluster: Mechanistic Aspects Relevant to HDS Catalysis

The kinetics of the reaction of a series of aromatic and aliphatic thiols with cluster 1 were determined. These reactions form cluster 2 and the arene or alkane corresponding to the thiol: Cp‘2Mo2Co2S3(CO)4 (1) + RSH → Cp‘2Mo2Co2S4(CO)2 (2) + RH + 2CO. These reactions are first order in thiol and first order in cluster 1 with appreciable negative entropies of activation. These data suggest that the rate determining step of the desulfurization reaction is the initial association of the thiol to the cluster. The more nucleophilic thiolate anions react with 1 at −40 °C to form an adduct in which the thiolate anion is bound η1 to the Co atom. At −25 °C, the initial adduct rearranges to a fluxional μ2, η1-bound thiolate. The fluxional process is proposed to involve a concerted “walking” of the thiolate and a μ2-bound sulfide ligand on the surface of the cluster. Near 35 °C, the thiolate−cluster adduct undergoes C−S bond homolysis to give the paramagnetic anion of cluster 1 and the phenyl or alkyl radical. The radical nature of the C−S bond cleavage was confirmed by the desulfurization of the radical clock reagents, cyclopropylmethanethiol and -thiolate anion, that form the cyclopropylmethyl radical which rearranged to the butenyl radical. The possible similarity in the C−S bond cleavage mechanism in these desulfurization reactions to those occurring in hydrodesulfurization (HDS) over Co/Mo/S catalysts is discussed.

Lifetime of the 1,4-Biradical Derived from Alkyl Phenylglyoxylate Triplets: An Estimation Using the Cyclopropylmethyl Radical Clock.

Lifetime of the 1,4-Biradical Derived from Alkyl Phenylglyoxylate Triplets: An Estimation Using the Cyclopropylmethyl Radical Clock.

Short-Lived 1,5-Biradicals Formed from Triplet 1-Alkoxy- and 1-(Benzyloxy)-9,10-anthraquinones

The cyclopropylmethyl and (trans-2-phenylcyclopropyl)methyl radical clocks were used to estimate the lifetimes of triplet state biradicals formed from substituted 1-alkoxy-9,10-anthraquinones by photoexcitation and subsequent 1,5-hydrogen atom transfer. Irradiation (350 nm) of 1-(cyclopropylmethoxy)-2-methyl-9,10-anthraquinone (1cp) in argon-purged methanol generated the primary anthrahydroquinone product (2). Upon exposure to air, 2 was rapidly converted to cyclopropanecarboxaldehyde and 1-hydroxy-2-X-9,10-anthraquinone (3). In contrast, irradiation of 1-{(trans-2-phenylcyclopropyl)methoxy}-2-benzyl-9,10-anthraquinone (1pcp) under similar conditions produced only small amounts of 3 and the corresponding aldehyde, trans-(2-phenylcyclopropyl)carboxaldehyde. In addition, products resulting from rearrangement of the 1,5-biradical to a homoallylic 1,8-biradical were also obtained. Using the known rate constant for the rearrangement of the phenylcyclopropylmethyl radical to the homoallylic radical and the obse...

Ion and Radical Rearrangements as a Probe of the Mechanism of a Surface Reaction: The Desulfurization of Cyclopropylmethanethiol and 3-Butene-1-thiol on Mo(110)

Rearrangement reactions were used to probe the transient intermediates in thiol desulfurization induced by Mo(110) by studying cyclopropylmethanethiol and 3-butene-1-thiol. Thiolate intermediates were identified in both cases using vibrational spectroscopy, which indicates facile S-H bond scission on Mo(110). Heterolytic C-S bond scission, leading to a cationic intermediate, is excluded based on the lack of rearrangement products in the reactions of 3-butene-1-thiolate and the absence of cyclobutane or cyclobutene in the reaction of cyclopropylmethyl thiolate on Mo(110). Hydrogenolysis without rearrangement is the primary pathway for both thiols investigated. The lack of rearrangement in the 3-butene-1-thiolate indicates that C-S bond scission and C-H bond formation occur nearly simultaneously. Evidence for the radical pathway is obtained from the production of 1,3-butadiene formed via the rearrangement of cyclopropylmethyl group following C-S bond scission in the cyclopropylmethyl thiolate and by related studies of cyclopropylmethyl bromide. The investigation of the cyclopropylmethyl bromide also demonstrates that trapping of the cyclopropylmethyl radical is favored over selective {beta}-dehydrogenation. This is the first study in which radical rearrangements have been used to obtain detailed information about the nature of extremely short-lived reactions in a surface process. 39 refs., 5 figs., 3 tabs.

Malonate radical cyclisations of methylenecyclopropane derivatives

Cyclisations of various methylenecyclopropyl substituted malonate radicals have been studied. Radicals derived from malonates 4 and 9 underwent exclusive 5- exo cyclisation onto the methylenecyclopropane alkene, followed by opening of the resulting cyclopropylmethyl radical, to give methylenecyclohexane products. Radicals derived from malonates 5 and 10 largely gave bicyclo[1.5.0]octane products, in good yields, as a result of 7- endo cyclisation. Cyclisation of the radical derived from malonate 11 gave a bicyclo[1.5.0]nonane derivative in 31% yield, as a result of an 8- endo cyclisation.

Radical reactions of epoxides. 2. intramolecular competition between cyclopropylmethyl and oxiranylmethyl radical ring‐opening rearrangements

AbstractThe erythro‐thioimidazole precursor to the cyclopropyloxiranylmethyl radical has been prepared. Treatment with 7–19 equiv. of triphenyltin hydride at 70°C gave only 3‐cyclopropylprop‐2‐en‐1‐ol, the product of epoxide ring opening. No product in which the cyclopropyl ring had opened was observed. Kinetic analysis allowed the assignment of a lower limit for the rate of oxiranylcarbinyl radical rearrangements of 1 × 1010 s−1 at this temperature.

A novel sequence of radical rearrangements involving the 5-exo cyclisation of a 3-(methylenecyclopropyl)propyl radical

Radical 10, generated from the corresponding imidazolethiocarbonyl derivative 3 or the phenyl selenide 4, rearranges in a six-step process to give the cyclohexene 5, after reduction; this rearrangement sequence includes the selective 5-Exo cyclisation of a (methylenecyclopropyl)propyl radical and opening of the intermediate cyclopropylmethyl radical to give a ring-expanded product.

Radical clocks as probes of 1,4-biradical intermediates in the photochemical cycloaddition reactions of 2-cyclopentenone with alkenes

The products of the photochemical reaction of 2-cyclopentenone with 1,6-heptadiene and with vinylcyclopropane have been examined. With 1,6-heptadiene the products were cyclobutanes, which arise from 2 + 2 photocycloaddition between the cyclopentenone carbon–carbon double bond and one of the two terminal double bonds of the heptadiene. The 1,4-biradical that is an intermediate in this reaction contains a derivative of a 1-hexenyl radical; no products derived from cyclization of this intermediate to a cyclopentylmethyl radical were observed. With vinylcyclopropane some of the products isolated also arose from 2 + 2 photocycloaddition; in addition, comparable quantities of products resulting from rearrangement of the intermediate 1,4-biradical were obtained. In this case the initially produced intermediate 1,4-biradical contains a cyclopropylmethyl radical that can rearrange to a homoallylic radical; the products isolated were derived from intramolecular disproportionation in the new 1,7-biradical containing the homoallylic radical. The rate constant for the rearrangement of the cyclopropylmethyl radical to the homoallylic radical is known and was used as a clock to estimate the lifetime of the initially produced 1,4-biradical. The value estimated is of the order of 50 ns. The structures of the products indicate that the initial bonding between the excited cyclopentenone and vinylcyclopropane takes place at both the α-position and the β-position of the enone and not exclusively at the α-position as a recent report claims. Keywords: enone photocycloaddition, 1,4-biradicals, radical clocks.

Transition-metal-centered radicals in organic synthesis. Titanium(III)-induced cyclization of epoxy olefins

We wish to report a solution to this problem which allows the direct synthesis of functionalized cyclopentane derivatives. This new reaction is based on an analogy to the extremely facile rearrangement of cyclopropylmethyl radical to homoallyl radical (eq 2). A a-complex of an epoxide with a paramagnetic transition metal4 having a half-filled (*-symmetry) d orbital represents an electronic analogue of the cyclopropylmethyl moiety. By analogy to eq 2, release of ring strain might be expected to drive the homolytic C-0 bond cleavage in eq 3.

Determination of the stabilization energy of the cyclopropylmethyl radical by EPR spectroscopy

AbstractCyclopropylmethyl radicals were generated from cyclopropylmethyl bromide and studied at low temperatures by EPR spectroscopy. From the exchange broadening in the spectra the internal rotation barrier about the C‐β‐C‐α. bond was found to be 11.5±0.8 kJ mol−1. Hence, the stabilization energy of the cyclopropylmethyl radical is 10±2.3 kJ mol−1 and DH° (cyclopropylmethyl‐H) = 400 kJ mol−1. The radical's structure, conformation and C‐β‐C‐α. rotation barrier were calculated by the semi‐empirical MNDO‐UHF method.