Remote Substituent Effects Research Articles

Synthesis of Functionalized Pyrans by Domino Metathesis Reaction of Oxabicyclo Derivatives: Dramatic Effect of Remote Substituents on Reactivity and Selectivity.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Radical-anionic cyclizations of enediynes: remarkable effects of benzannelation and remote substituents on cyclorearomatization reactions.

The reasons for large changes in the energetics of C1-C5 and C1-C6 (Bergman) cyclizations of enediynes upon one-electron reduction were studied by DFT and Coupled Cluster computations. Although both of these radical-anionic cyclizations are significantly accelerated relative to their thermal counterparts, the acceleration is especially large for benzannelated enediynes, whose reductive cyclizations are predicted to proceed readily under ambient conditions. Unlike their thermal analogues, the radical-anionic reactions can be efficiently controlled by remote substitution, and the effect of substituent electronegativity is opposite of the effect on the thermal cycloaromatization reactions. For both radical-anionic cyclizations, large effects of benzannelation and increased sensitivity to the properties of remote substituents result from crossing of out-of-plane and in-plane MOs in the vicinity of transition states. This crossing leads to restoration of the aromaticity decreased upon one-electron reduction of benzannelated enediynes. Increased interactions between nonbonding orbitals as well as formation of new aromatic rings (five membered for the C1-C5 cyclization and six membered for C1-C6 cyclizations) are the other sources of increased exothermicity for both radical-anionic cyclizations. The tradeoff between reduction potentials and cyclization efficiency as well as the possibilities of switching of enediyne cyclization modes (exo or C1-C5 vs endo or C1-C6)) under kinetic or thermodynamic control conditions are also outlined.

Remote substituent effects on N-X (X = H, F, Cl, CH3, Li) bond dissociation energies in para-substituted anilines.

UB3LYP/6-311++g**//UB3LYP/6-31+g* and ROMP2/6-311++g**//UB3LYP/6-31+g* methods were used to calculate (i) N-X bond dissociation energies (BDE) in 4-YC6H4NH-X and (ii) N-H BDEs in 4-YC6H4NU-H, where Y = H, Me, OCH3, SMe, NH2, NMe2, SiMe3, F, Cl, CN, COOH, CF3, and NO2, X = H, CH3, F, Cl, and Li, and U = H, F, and CH(3). It was found that N-H BDEs of 4-YC6H4NH2 have a positive correlation with the substituent sigma(p+) constants. The slope (rho+) is about 3.0-4.3 kcal/mol, which is in good agreement with the experimental results. It was also found that the substituent effects on N-X BDEs of 4-YC6H4NH-X change considerably when X changes. rho(+)values for N-CH3, N-F, N-Cl, and N-Li BDEs were calculated to be 3.1-4.6, 1.3-1.9, 1.8-2.6, and 4.9-6.8 kcal/mol, respectively. The reason for the variation of substituent effects was proposed to be the ground-state effect, i.e., the interaction between the intact NH-X moiety and the parasubstituents. Finally, alpha-substitution was found to be able to significantly change the substituent effects. rho(+)values for N-H BDEs of 4-C6H4NCH3(-)H and 4-C6H4NF-H are 2.5-4.0 and 1.7-1.9 kcal/mol, respectively.

Structures of the X−Y−NO Molecules and Homolytic Dissociation Energies of the Y−NO Bonds (Y = C, N, O, S)

High-level theoretical methods (UB3LYP/6-311++g(2df,p), RMP2/6-311++g(d,p), CBS-4M, CBS-Q, and G3) were used to study the structures and bond dissociation energies (BDE) of the X−Y−NO molecules. The data were used to evaluate the previous experimental and theoretical results. It was found that the syn conformation is favored by CH3−Y−NO, C2H5−Y−NO, and CH3O−Y−NO (Y = C, N, O, S), whereas the anti conformation is favored by CH3CO−Y−NO and Ph-Y−NO (Y = C, N, O). For Ph−S−NO, the syn conformation is preferred because of the long S−N bond. When X is an alkyl substituent, the Y−NO BDEs increase in the order X−S−NO (∼30 kcal/mol) < X−CH2−NO (∼40 kcal/mol) < X−O−NO (∼43 kcal/mol) < X−NH−NO (48 kcal/mol). When X is an aromatic substituent, the Y−NO BDEs increase in the order X−O−NO (∼21 kcal/mol) < X−S−NO (26 kcal/mol) < X−CH2−NO (∼30 kcal/mol) < X−NH−NO (∼35 kcal/mol). The solvent effects of acetonitrile on the free energy change of C−NO and N−NO homolysis are significant, which are about 3−5 kcal/mol. The solvent effects of acetonitrile on the free energy change of O−NO and S−NO homolysis are relatively small, which are about 1−2 kcal/mol. Finally, we found that the remote substituent effects on C−NO, N−NO, O−NO, and S−NO BDEs have ρ+ values of −0.4∼−0.9, 1.7−1.8, 3.2−3.9, and 1.2−1.7 kcal/mol. These values are significantly different from those on the C−H (0.4−0.6 kcal/mol), N−H (3.4−4.6 kcal/mol), O−H (4.1−5.7 kcal/mol), and S−H (2.0−3.8 kcal/mol) BDEs. Therefore, the ground effects are important for the net substituent effects on BDEs.

Synthesis of functionalized pyrans by domino metathesis reaction of oxabicyclo derivatives: dramatic effect of remote substituents on reactivity and selectivity.

Synthesis of functionalized pyrans by domino metathesis reaction of oxabicyclo derivatives: dramatic effect of remote substituents on reactivity and selectivity.

Remote substituent effect in palladium/pyridinyl-oxazolines catalyzed asymmetric allylic alkylation

The chiral ligands containing pyridinyl moieties and oxazolines bridged by disubstituted methylene 2– 4 were prepared and they provided ee values 17–68% higher than unsubstituted analogues 1 in the palladium-catalyzed enantioselective allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate.

Remote substituent effects on bond dissociation energies of para-substituted aromatic silanes.

UB3LYP/6-31G(d) and ROMP2/6-311++G(d,2p) methods were used to calculate the Si-X bond dissociation energies (BDEs) of a number of para-substituted aromatic silanes (4-Y-C(6)H(4)-SiH(2)X, where X = H, F, Cl, or Li). It was found that the substituent effect on the Si-H BDE of 4-Y-C(6)H(4)-SiH(3) was small, as the slope (rho(+)()) of the BDE- regression was only 0.09 kJ/mol. In comparison, the substituent effect on the Si-F BDE of 4-Y-C(6)H(4)-SiH(2)F was much stronger, whose rho(+ )()value was -2.34 kJ/mol. The substituent effect on the Si-Cl BDE of 4-Y-C(6)H(4)-SiH(2)Cl was also found to be strong with a rho(+)() value of -1.70 kJ/mol. However, the substituent effect on the Si-Li BDE of 4-Y-C(6)H(4)-SiH(2)Li was found to have a large and positive slope (+9.12 kJ/mol) against. The origin of the above remarkably different substituent effects on the Si-X BDEs was found to be associated with the ability of the substituent to stabilize or destabilize the starting material (4-Y-C(6)H(4)-SiH(2)X) as well as the product (4-Y-C(6)H(4)-SiH(2)* radical) of the homolysis. Therefore, the direction and magnitude of the effects of Y-substituents on the Z-X BDEs in compounds such as 4-YC(6)H(4)Z-X should have some important dependence on the polarity of the Z-X bond undergoing homolysis. This conclusion was in agreement with that from earlier studies (for example, J. Am. Chem. Soc. 1991, 113, 9363). However, it indicated that the proposal from a recent work (J. Am. Chem. Soc. 2001, 123, 5518) was unfortunately not justified.

Preparation of orthogonally protected chitosan oligosaccharides: observation of an anomalous remote substituent effect

Orthogonally protected chitosan tetrasaccharides were synthesized in a convergent fashion by trichloroacetimidate activation. The anomeric substituent at the reducing end of the disaccharide acceptor has a remarkably strong influence on glycosidic coupling; a thiophenyl-substituted disaccharide was observed to be an unusually poor glycosyl acceptor in comparison with the corresponding allyloxy-substituted disaccharide.

Remote ligand substituent effects on the properties of oxo-Mo(V) centers with a single ene-1,2-dithiolate ligand

The oxomolybdenum mono-ene-1,2-dithiolate complex (Tp*)MoO(bdtCl 2) ( 3) has been synthesized and characterized (Tp* is hydrotris(3,5-dimethyl-1-pyrazolyl)borate; bdtCl 2 is 3,6-dichloro-1,2-benzenedithiolate). The X-ray structural data show that 3 crystallizes in the monoclinic space group, P2 1/ c, where a=7.963 (3), b=26.272 (11), c=14.016 (6) Å, β=105.352 (7). The (Tp*)MoO(bdtCl 2) molecule exhibits a distorted pseudo-octahedral coordination geometry, with the Mo atom ligated by a terminal oxo atom, two sulfur donor atoms of the bdtCl 2 ligand and three nitrogen atoms of the tridentate facially coordinated Tp* ligand. The coordination environment about the Mo atom is similar to that of (Tp*)MoO(bdt) ( 1) (bdt is 1,2-benzenedithiolate), but the fold angle between the MoS 2 plane and S 2C 2 plane of the bdtCl 2 ligand ( θ=6.9°) is substantially smaller than the feature in 1 ( θ=21.3°). The similar IR, EPR, and electronic absorption spectroscopic results for 1 and 3 indicate that the electron withdrawing nature of the chlorine substituents of 3 does not significantly perturb the electronic structure of the Mo(V) center. However, the solution redox potentials and the gas-phase ionization energies are sensitive to remote substituent effects.

Remote substituent effects on regioselectivity in the Pauson–Khand reaction of 2-substituted norbornenes

The effect of a remote substituent on the regioselectivity in the Pauson–Khand reaction of 2-substituted norbornenes has been investigated. Moderate level of regioselectivity was observed and the regioselectivity increases as the electron-withdrawing power of the remote substituent increases. exo Substituents at C-2 of norbornenes generally gave a higher regioselectivity than the endo substituents.

Effect of solvent and remote ligand substituents on the photochemical behaviour of copper(II) dithiocarbamates and dithiophosphates

The photochemical properties of bis(dithiocarbamato)CuII, Cu(R1dtc)2, and bis(dithiophosphato)CuII, Cu(R22dtp)2, complexes with different remote ligand substituents (R1 = piperidine, morpholine, pyrrolidine and 4-phenylpiperazine; R2 = Me, Et and i-Pr) have been studied in chloromethanes (CCl4, CHCl3, CH2Cl2), chloromethanes/EtOH and PhMe. The monomeric species CuII(R1dtc)Cl and its chloride-bridged dimeric form Cu2(R1dtc)2Cl2 were subsequently obtained during Cu(R1dtc)2 photolysis in chloromethane/EtOH mixtures and the steady-state concentration of Cu2(R1dtc)2Cl2 was found to depend on the EtOH content in the mixed solvents as well as on the nature of R1 and the oxidising ability of the chloromethane. The appearance of the mixed-ligand complex CuII(R22dtp)Cl has been observed as an intermediate photoproduct after longer u.v.-irradiation of Cu(R22dtp)2 in chloromethanes/EtOH.

Ruthenium-catalyzed [2 + 2] cycloadditions of 2-substituted norbornenes.

The studies of remote substituent effects in controlling regio- and stereoselectivities in chemical reactions provide important information in understanding long-range stereoelectronic effects. The effect of remote substituents on ruthenium-catalyzed [2 + 2] cycloadditions of 2-substituted norbornenes has been investigated. The cycloadditions occurred at room temperature in excellent yields, and regioselectivities of 1.2:1 to 7.5:1 were observed with various 2-substituted norbornenes.

Chiral action at a distance: remote substituent effects on the optical activity of calyculins A and B.

[structure--see text] Calyculins A and B differ only by the (E)- vs (Z)-configuration at C(2). Yet, they show a large difference in optical rotations. We demonstrate a new strategy that provides a physical analysis of this long-range chiro-optical effect by Boltzmann-averaged atomic contribution mapping. The polarizability characteristics of the CN substituent rather than the perturbation of the stereogenic centers or the introduction of asymmetry into the polyene chain give rise to the remarkable difference in rotation angles.

Reaction kinetics of electrogenerated 9,10-bis(4-substituted-phenyl)anthracene cation radicals with methanol: A change in mechanism brought about by remote substituents

The reactions of 9,10-bis(4-nitrophenyl)- and 9,10-bis(4-methoxyphenyl)anthracene cation radicals (DNA˙+ and DAA˙+) with methanol (MeOH) in acetonitrile were analyzed using a pulse electrolysis stopped-flow method. The reaction of DNA˙+ was found to proceed via the same rate law as the 9,10-diphenylanthracene cation radical (DPA˙+), i.e. −d[DNA˙+]/dt = k[DNA˙+][MeOH]2, with a reaction rate 6 times faster. In contrast, the rate law governing the reaction of DAA˙+ with MeOH was different from that of DPA˙+, and was found to be −d[DAA˙+]/dt = k[DAA˙+]2[MeOH]. Reflecting this difference in the rate laws, an acceleration of the reaction was observed in the decay of DAA˙+ relative to DPA˙+, though methoxy groups usually stabilize aromatic cation radicals. This unusual remote substituent effect, which involves a change in the reaction mechanism, is discussed in terms of stabilization of intermediates in the proposed reaction mechanisms.

ChemInform Abstract: Remote Substituent Effects on the Enantiomeric Excess of Intramolecular Asymmetric Palladium‐Catalyzed Polyene Cyclizations.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Remote Substituent Effects on the Enantiomeric Excess of Intramolecular Asymmetric Palladium-Catalyzed Polyene Cyclizations

Remote Substituent Effects on the Enantiomeric Excess of Intramolecular Asymmetric Palladium-Catalyzed Polyene Cyclizations

The effect of remote substituents in free radical addition reactions: new evidence for the penultimate unit effect

Ab initio molecular orbital calculations of the barrier for the addition of gamma-substituted propyl radicals to various alkenes indicate that substituents at the gamma position of a radical can significantly affect the barrier. This finding supports recent experimental evidence for an enthalpic penultimate unit effect in free-radical copolymerization. For the reactions studied in the present work, this penultimate unit effect is consistent with a significant polar contribution.

Effects of Adjacent Onium Cations and Remote Substituents on the H−A+ Bond Equilibrium Acidities in Dimethyl Sulfoxide Solution. An Extensive Ylide Thermodynamic Stability Scale and Implication for the Importance of Resonance Effect on Ylide Stabilities

The equilibrium acidities (pKas) of six families of remotely substituted benzyl onium salts (i.e., 4-G-C6H4CH2-E+·Br-, where E+ = Ph3P+, Ph2PO, Et3N+, Me2S+, Me2Se+, and Bu2Te+ and G = H, Me, CF3, CO2Me, CN, and NO2), one family of α-E+ substituted acetophenones (i.e., PhCOCH2-E+·Br-, where E+ = Me2S+, Bu2Te+, Bu3P+, and Ph3As+), and one family of 9-E+-substituted fluorenes (i.e., 9-E+-FlH·Br-, where E+ = Bu2S+, Me2Se+, Bu2Te+, Bu3P+, and Ph3As+) have been determined in a single solvent, dimethyl sulfoxide (DMSO). This allowed meaningful comparisons of the thermodynamic stabilities for an extensive range of Group VB and VIB ylides covering up to six elements (N, P, As; S, Se, Te) to be made for the first time on the basis of a unified standard. A comparison of the pKa values of onium salts with those of their parents shows that all the onium substituents studied in the present work are strongly ylide-stabilizing, covering an anion stabilization energy range of 17−35 kcal/mol (i.e., ΔpK = 12−25 pK units). A further examination of the pKa values also reveals that the thermodynamic stabilities of the Group VB onium ylides are in a decreasing order of P+−C- > As+−C- > N+−C- and of the Group VIB onium ylides in a decreasing order of S+−C- > Se+−C- ∼ Te+−C-, if the substituents on the onium atoms are kept similar. The stability order for the ylides of the third-row elements was found to be S+−C- > P+−C-, as implied by the ΔpKs of 1.7−4.2 for the three R3P+−C-/R2S+−C- pairs compared (see text). The pKas of the eight remotely substituted E+-CH2Ar series all correlate well with the σ- constants (see Table 3) with a decreasing order of slopes as (E+ =) Ph2P(O) (−5.86) > Ph3As+ (−5.35) > Bu3P+ (−5.00) > Ph3P+(−4.46) and Bu2Te+ (−5.50) > Me2Se+ (−5.03) > Me2S+ (−3.40), suggesting a similar trend for the extent of charge localization at the carbanions next to the E+ group. All these observations are consistent with the assumption that at least part of the gained stabilization in the phosphonium and sulfonium ylide cases (especially the latter) has to be attributed to the back-bonding stabilization involving the σ* and/or 3d orbital participation. Discussion for elucidating this view is presented.

ChemInform Abstract: Stereoselective Alkylations in Rigid Systems. Effect of Remote Substituents on π‐Facial Additions to Lactam Enolates. Stereoselectronic and Steric Effects.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Remote Substituent Effects on the Reactivity of 9-Aryl- and 9,10-Diarylanthracene Radical Cations with Anions and Amines

Radical cations of 9-aryl- and 9,10-diarylanthracenes with substituents on the 4 position of the aryl rings (PA-X•+ and DPA-X•+, respectively) have been generated by photoionization in acetonitrile...