Hydrogen bond energy estimation (H-BEE) in large molecular clusters: A Python program for quantum chemical investigations.

A procedure, derived from the fragmentation-based molecular tailoring approach (MTA), has been proposed and extensively applied by Deshmukh and Gadre for directly estimating the individual hydrogen bond (HB) energies and cooperativity contributions in molecular clusters. However, the manual fragmentation and high computational cost of correlated quantum chemical methods make the application of this method to large molecular clusters quite formidable. In this article, we report an in-house developed software for automated hydrogen bond energy estimation (H-BEE) in large molecular clusters. This user-friendly software is essentially written in Python and executed on a Linux platform with the Gaussian package at the backend. Two approximations to the MTA-based procedure, viz. the first spherical shell (SS1) and the Fragments-in-Fragments (Frags-in-Frags), enabling cost-effective, automated evaluation of HB energies and cooperativity contributions, are also implemented in this software. The software has been extensively tested on a variety of molecular clusters and is expected to be of immense use, especially in conjunction with correlated methods such as MP2, CCSD(T), and so forth.

Green Synthesis of Electrophilic Alkenes Using a Magnesium Catalyst under Aqueous Conditions and Mechanistic Insights by Density Functional Theory.

A green approach for the synthesis of electrophilic alkenes has been developed via Knoevenagel condensation between active methylene compounds and carbonyl compounds using Mg powder under aqueous conditions. In this strategy, Mg(OH)2 acts as a catalyst, which was generated in situ by the reaction between metallic Mg (20 mol %) and water. Mg was found to be an efficient, nontoxic, and inexpensive metal catalyst system for producing a range of electrophilic alkenes in excellent yields (≤98%). A gram-scale synthesis of electrophilic alkenes has been developed, and Mg metal was recovered and recycled up to three times without an appreciable loss of catalytic activity. A catalytic cycle was proposed, and the reaction mechanism was investigated using density functional theory. The key steps are enolization of ethyl cyanoacetate, C-C bond formation, and then regeneration of the catalyst via metathesis with H2O. The overall reaction occurs easily with a maximum ΔG°â§§ value of 7.9 kcal/mol for the rate-determining C-C bond formation step. Our protocol has several advantages and can be further extended to one-pot sequential Knoevenagel condensation and Michael addition, and one-pot sequential Knoevenagel condensation and chemoselective reduction can be used for the synthesis of valuable precursors of pharmaceutical products under green and aqueous conditions.

Interplay of Hydrogen, Pnicogen, and Chalcogen Bonding in X(H2O)n=1-5 (X = NO, NO+, and NO-) Complexes: Energetics Insights via a Molecular Tailoring Approach.

Nitric oxide (NO) and its redox congeners (NO+ and NO-), designated as X, play vital roles in various atmospheric and biological events. Understanding the interaction between X and water is inevitable to explain the different reactions that occur during these events. The present study is a unified attempt to explore the noncovalent interactions in microhydrated networks of X using the MP2/aug-cc-pVTZ//MP2/6-311++G(d,p) level of theory. The interactions between X and water have been probed by the molecular electrostatic potential (MESP) by exploiting the features of the most positive (Vmax) and most negative potential (Vmin) sites. The individual energy and cooperativity contributions of various types of noncovalent interactions present in X(H2O)n=1-5 complexes are estimated with the help of a molecular tailoring-based approach (MTA-based). The MTA-based analysis reveals that among various possible interactions in NO(H2O)n complexes, the water···water hydrogen bonds (HBs) are the strongest. Neutral NO can form hydrogen and pnicogen bonds (PBs) with water depending on the orientation; however, such HBs and PBs are the weakest. On the other hand, in the NO+(H2O)n complexes, the NO+···water interactions that occur through PBs are the strongest; the next one is the chalcogen bonding (CB), and the water···water HBs are the weakest. In the case of the NO-(H2O)n complexes, the HB interactions via both N and O atoms of NO- and water molecules are the strongest ones. The strength of water···water HB interactions is also seen to increase with the increase in the number of water molecules in NO-(H2O)n. The present study exemplifies the applicability of MTA-based calculations for quantifying various types of individual noncovalent interactions and their interplay in microhydrated networks of NO and its related ions.

Palladium(II)-Catalyzed Decarboxylative Difunctionalization of Alkynoic Acids To Access (E)-ß-Sulfonylacrylamides and DFT Study.

A palladium(II)-catalyzed regio- and stereoselective difunctionalization of alkynoic acids has been achieved using sodium sulfinates and isocyanides to synthesize (E)-ß-sulfonylacrylamides. The reaction proceeds via decarboxylative isocyanide addition, followed by sulfonylation. This three-component process works well with aromatic, heteroaromatic, and aliphatic alkynoic acids with good functional group tolerance and excellent regio- and stereoselectivity. DFT calculations were carried out to explain the reaction mechanism and the stereoselective formation of (E)-ß-sulfonylacrylamides.

On the Short-Range Nature of Cooperativity in Hydrogen-Bonded Large Molecular Clusters.

The variation in the hydrogen bond (HB) strength has considerable consequences on the physicochemical properties of molecular clusters. Such a variation mainly arises due to the cooperative/anti-cooperative networking effect of neighboring molecules connected by HBs. In the present work, we systematically study the effect of neighboring molecules on the strength of an individual HB and the respective cooperativity contribution toward each of them in a variety of molecular clusters. For this purpose, we propose a use of a small model of a large molecular cluster called the spherical shell-1 (SS1) model. This SS1 model is constructed by placingg the spheres of an appropriate radius centered on X and Y atoms of the X-H···Y HB under consideration. The molecules falling within these spheres constitute the SS1 model. Utilizing this SS1 model, the individual HB energies are calculated within the molecular tailoring approach-based framework and the results are compared with their actual counterparts. It is found that the SS1 is a reasonably good model of large molecular clusters, providing 81-99% of the total HB energy estimated using the actual molecular clusters. This in turn suggests that the maximum cooperativity contribution toward a particular HB is due to the fewer number of molecules (in the SS1 model) directly interacting with two molecules involved in its formation. We further demonstrate that the remaining part of the energy or cooperativity (∼1 to 19%) is captured by the molecules falling in the second spherical shell (SS2) centered on the hetero-atom of the molecules in the SS1 model. The effect of increasing size of a cluster on the strength of a particular HB, calculated by the SS1 model, is also investigated. The calculated value of the HB energy remains unchanged with the increase in the size of a cluster, emphasizing the short-ranged nature of the HB cooperativity in neutral molecular clusters.

Fragments-in-fragments method for efficient and reliable estimates of individual hydrogen bond energies in large molecular clusters.

The knowledge of individual hydrogen bond (HB) strength in molecular clusters is indispensable to get insights into the bulk properties of condensed systems. Recently, we have developed the molecular tailoring approach based (MTA-based) method for the estimation of individual HB energy in molecular clusters. However, the direct use of this MTA-based method to large molecular clusters becomes progressively difficult with the increase in the size of a cluster. To overcome this caveat, herein, we propose the use of linear scaling method (such as the original MTA method) for the estimation of single-point (SP) energies of large-sized parent molecular cluster and their respective fragments. Because the fragments of the MTA-based method, for the estimation of HB energy, are further fragmented, this proposed strategy is called as Fragments-in-Fragments (Frags-in-Frags) method. The SP energies of fragments and parent cluster calculated by the Frags-in-Frags approach were utilized to estimate the individual HB energy. The estimated individual HB energies, in various molecular clusters, by Frags-in-Frags method are found to be in excellent linear agreement with their MTA-based counterparts (R2 = 0.9975 of 348 data points). The difference being less than 0.5 kcal/mol in most of the cases. Furthermore, RMSD is 0.43 kcal/mol, MAE is 0.33 kcal/mol, and the standard deviation is 0.44 kcal/mol. Importantly, the Frags-in-Frags method not only enables the reliable estimation of HB energy in large molecular clusters but also requires less computational time and can be possible even with off-the-shelf hardware.

Characterization of non-covalent contacts in mono- and di-halo substituted acetaldehydes: probing the substitution effects of electron donating and withdrawing groups.

In the current work, a systematic evaluation of the different types of non-covalent interactions (NCIs) in acetaldehyde dimers, including dimers of mono-halo (XCH2CHO)2, di-halo (X2CHCHO)2 and tri-halo substituted (X3CCHO)2 acetaldehydes via the associated stabilization energy of these dimers has been performed. Furthermore, a topological analysis of the electron density based on the quantum theory of atoms in molecules (QTAIM) and non-covalent interaction reduced density gradient (NCI-RDG) isosurfaces has also been performed to evaluate the nature of these NCIs. The geometrical and electronic characteristics have been evaluated via the presence of different electron-donating groups (EDGs) and electron-withdrawing groups (EWGs) or substituents in dimers of these molecules, namely, XCH(Y)CHO and X2C(Y)CHO (wherein X = -F, -Cl, and -Br and Y = -SO3H, -CN, -NO2, -NH2, -CH3, -OCH3, and -SMe3). The C-H⋯O, C-H⋯X, X⋯X, X⋯O and C⋯O tetrel bonded contacts have been recognized to play an important role in the stabilization of the formed dimers. This study also establishes the fact that the overall stability of the dimeric assemblies is governed by the contributions from the mutual and complex interplay of a variety of interactions in the investigated dimers. Hence considerations based on strong H-bond donor-acceptor characteristics hold relevance for simple systems only, but slight alteration in the electronic environment can affect the overall stabilization energies of the system being investigated and the nature of the interactions that contribute towards the same.

Two-Step ONIOM Method for the Accurate Estimation of Individual Hydrogen Bond Energy in Large Molecular Clusters.

The study of molecular clusters to understand the properties of condensed systems has been the subject of immense interest. To get insight into these properties, the knowledge of various noncovalent interactions present in these molecular clusters is indispensable. Our recently developed molecular tailoring approach-based (MTA-based) method for the estimation of the individual hydrogen bond (HB) energy in molecular clusters is useful for this purpose. However, the direct application of this MTA-based method becomes progressively difficult with the increase in the size of the cluster. This is because of the difficulty in the evaluation of single-point energy at the correlated level of theory. To overcome this caveat, herein, we propose a two-step method within the our own N-layer integrated molecular orbital molecular mechanics (ONIOM) framework. In this method, the HB energy evaluated by the MTA-based method employing the actual molecular cluster at a low Hartree-Fock (HF) level of theory is added to the difference in the HB energies evaluated by the MTA-based method, employing an appropriate small model system, called the shell-1 model, calculated at high (MP2) and low (HF) levels of theory. The shell-1 model of a large molecular cluster is made up of only a few molecules that are in direct contact (by a single HB) with the two molecules involved in the formation of an HB under consideration. We tested this proposed two-step ONIOM method to estimate the individual HB energies in various molecular clusters, viz., water (Wn, n = 10-16, 18 and 20), (H2O2)12, (H2O3)8, (NH3)n and strongly interacting (HF)15 and (HF)m(W)n clusters. Furthermore, these estimated individual HB energies by the ONIOM method are compared with those calculated by the MTA-based method using actual molecular clusters. The estimated individual HB energies by the ONIOM method, in all these clusters, are in excellent linear one-to-one agreement (R2 = 0.9996) with those calculated by the MTA-based method using actual molecular clusters. Furthermore, the small values of root-mean-square deviation (0.06), mean absolute error (0.04), |ΔEmax| (0.21) and Sε (0.06) suggest that this two-step ONIOM method is a pragmatic approach to provide accurate estimates of individual HB energies in large molecular clusters.

One-pot C-C, C-N, and C-S bond construction for synthesis of 3-sulfenylindoles directly from unactivated anilines involving dual palladium catalysis and mechanistic insights from DFT.

An efficient dual Pd-catalytic system was developed for one-pot synthesis of 3-sulfenylindoles via C-C, C-N and C-S bond construction directly from unactivated 2-iodo(NH)anilines under mild reaction conditions. Furthermore, 3-selenyl/halo/carbon-functionalized indoles were synthesized in good yields and a short reaction time. The synthetic utility of 3-sulfenylindole was also demonstrated. The key role of solvent in palladium catalysis was unravelled by DFT.

A Tug of War between the Self- and Cross-associating Hydrogen Bonds in Neutral Ammonia-Water Clusters: Energetic Insights by Molecular Tailoring Approach.

In the present work, the energies of various types of individual HBs observed in neutral (NH3 )m (H2 O)n , (m+n=2 to 7) clusters were estimated using the molecular tailoring approach (MTA)-based method. The calculated individual HB energies suggest that the O-H…N HBs are the strongest (1.21 to 12.49 kcal mol-1 ). The next ones are the O-H…O (3.97 to 9.30 kcal mol-1 ) HBs. The strengths of N-H…N (1.09 to 5.29 kcal mol-1 ) and N-H…O (2.85 to 5.56 kcal mol-1 ) HBs are the weakest. The HB energies in dimers also follow this rank ordering. However, the HB energies in dimers are much smaller than those obtained by the MTA-based method due to the loss in cooperativity contribution in the dimers. Thus, the calculated cooperativity contributions, for different types of HBs, fall in the range 0.64 to 5.73 kcal mol-1 . We wish to emphasize based on the energetic rank ordering obtained by the MTA-based method that the O-H of water is a better HB donor than the N-H of ammonia. The reasons for the observed energetic rank ordering are two folds: (i) intrinsically stronger O-H…N HBs than the O-H…O ones as revealed by dimer energies and (ii) the higher cooperativity contribution in the former than the later ones. Indeed, the MTA-based method is useful in providing the missing energetic rank ordering of various type of HBs in neutral (NH3 )m (H2 O)n clusters, in the literature.

Hydration shell model for expeditious and reliable individual hydrogen bond energies in large water clusters.

Recently, we have developed and tested a method, based on the molecular tailoring approach (MTA-based) to directly estimate the individual hydrogen bond (HB) energies in molecular clusters. Application of this MTA-based method to large molecular clusters is prohibitively difficult due to the evaluation of the energy of large-sized fragments. We propose here a smaller model system called the shell model, to overcome this difficulty. The shell model represents the first hydration shell of water molecules involved in the formation of HB under consideration. Utilizing the shell model as a parent system, fragmentation is carried out, in a fashion similar to the actual MTA-based method, to estimate individual HB energies in large water clusters (Wn, n = 10-16, 18 and 20). The estimated individual HB energies in these Wn clusters, employing the shell model, fall between 0.2 and 12.5 kcal mol-1 at the MP2/aug-cc-pVTZ level, with no net loss in the cooperativity contribution. We have also applied this shell model-based approach to estimate individual HB energies in the two lowest energy conformers of ammonia octamers (NH3)8 and mixed hydrogen fluoride-water clusters. The estimated individual HB energies employing the shell model, in all these molecular clusters studied in this work, are in good agreement with their actual MTA-based counterparts. The typical difference is less than 1 kcal mol-1. Importantly, the shell model has a huge computational time advantage over the actual MTA-based method and it requires only modest hardware.

Energetic Ordering of Hydrogen Bond Strengths in Methanol-Water Clusters: Insights via Molecular Tailoring Approach.

In this work, we examine the strength of various types of individual hydrogen bond (HB) in mixed methanol-water Mn Wm , (n+m=2 to 7) clusters, with an aim to understand the relative order of their strength, using our recently proposed molecular tailoring-based approach (MTA). Among all the types of HB, it is observed that the OM -H…OW HBs are the strongest (6.9 to 12.4 kcal mol-1 ). The next ones are OM -H…OM HBs (6.5 to 11.6 kcal mol-1 ). The OW -H…OW (0.2 to 10.9 kcal mol-1 ) and OW -H…OM HBs (0.3 to 10.3 kcal mol-1 ) are the weakest ones. This energetic ordering of HBs is seen to be different from the respective HB energies in the dimer i. e., OM -H…OM (5.0 to 6.0 kcal mol-1 )>OW -H…OM (1.5 to 6.0 kcal mol-1 )>OM -H…OW (3.8 to 5.6 kcal mol-1 )>OW -H…OW (1.2 to 5.0 kcal mol-1 ). The plausible reason for the difference in the HB energy ordering may be attributed to the increase or decrease in HB strengths due to the formation of cooperative or anti-cooperative HB networks. For instance, the cooperativity contribution towards the different types of HB follows: OM -H…OW (2.4 to 8.6 kcal mol-1 )>OM -H…OM (1.3 to 6.3 kcal mol-1 )>OW -H…OW (-1.0 to 6.5 kcal mol-1 )>OW -H…OM (-1.2 to 5.3 kcal mol-1 ). This ordering of cooperativity contribution is similar to the HB energy ordering obtained by the MTA-based method. It is emphasized here that, the interplay between the cooperative and anti-cooperative contributions are indispensable for the correct energetic ordering of these HBs.

Unusually Large Hydrogen-Bond Cooperativity in Hydrogen Fluoride Clusters, (HF)n, n = 3 to 8, Revealed by the Molecular Tailoring Approach.

In this work, our recently proposed molecular tailoring approach (MTA)-based method is employed for the evaluation of individual hydrogen-bond (HB) energies in linear (L) and cyclic (C) hydrogen fluoride clusters, (HF)n (n = 3 to 8). The estimated individual HB energies calculated at the MP2(full)/aug-cc-pVTZ level for the L-(HF)n are between 6.2 to 9.5 kcal/mol and those in the C-(HF)n lie between 7.9 to 11.4 kcal/mol. The zero-point energy corrections and basis set superposition corrections are found to be very small (less than 0.6 and 1.2 kcal/mol, respectively). The cooperativity contribution toward individual HBs is seen to fall between 1.0 to 4.8 kcal/mol and 3.2 to 6.9 kcal/mol for linear and cyclic clusters, respectively. Interestingly, the HB energies in dimers, cleaved from these clusters, lie in a narrow range (4.4 to 5.2 kcal/mol) suggesting that the large HB strength in (HF)n clusters is mainly due to the large cooperativity contribution, especially for n ≥ 5 (50 to 62% of the HBs energy). Furthermore, the HB energies in these clusters show a good qualitative correlation with geometrical parameters (H···F distance and F-H···F angles), stretching frequencies of F-H bonds, and electron density values at the (3, -1) bond critical points.

Appraisal of individual hydrogen bond strengths and cooperativity in ammonia clusters via a molecular tailoring approach.

In this work, we propose and test a method, based on the molecular tailoring approach (MTA), for the evaluation of individual hydrogen bond (HB) energies in ammonia (NH3)n clusters. This methodology was tested, in our earlier work, on water clusters. Liquid ammonia being a universal, non-aqueous ionizing solvent, such information of individual HB strength is indispensable in many studies. The estimated HB energies by an MTA-based method, in (NH3)n for n = 3-8, were calculated to be in the range of 0.65 to 5.54 kcal mol-1 with the cooperativity contribution falling between -0.54 and 1.88 kcal mol-1 both calculated at the MP2(full)/aug-cc-pVTZ level of theory. It is seen that the strong HBs in (NH3)n clusters were additionally strengthened by the large contribution of HB cooperativity. The accuracy of these estimated HB energies was validated by approximately estimating the molecular energy of a given cluster by adding the sum of HB energies to the sum of monomer energies. This approximately estimated molecular energy of a given cluster was found to be in excellent agreement with the actual calculated values. The negligibly small difference (less than 5.6 kcal mol-1) in these two values suggests that the estimated individual HB energies in ammonia clusters are quite reliable. Furthermore, these estimated HB energies by MTA are in excellent qualitative agreement with the other indirect measures of HB strength, such as HB bond distances and angles, N-H stretching frequency and the electron density values at the (3,-1) bond critical points.

Molecular Tailoring Approach for Estimating Individual Intermolecular Interaction Energies in Benzene Clusters.

There is no general method available for the estimation of individual intermolecular interaction energies in weakly bound molecular clusters, and such studies are limited only to the dimer. Recently, we proposed a molecular tailoring approach-based method for the estimation of individual O-H···O hydrogen bond energies in water clusters. In the present work, we extend the applicability of this method for estimating the individual intermolecular interaction energies in benzene clusters, which are expected to be small. The basis set superposition error (BSSE)-corrected individual intermolecular interaction energies in linear (LN) benzene clusters, LN-(Bz)n n = 3-7, were calculated to be in the range from -1.75 to -2.33 kcal/mol with the cooperativity contribution falling between 0.05 and 0.20 kcal/mol, calculated at the MP2.5/aug-cc-pVDZ level of theory. In the case of non-linear (NLN) benzene clusters, NLN-(Bz)n n = 3-5, the BSSE-corrected individual intermolecular interaction energies exhibit a wider range from -1.16 to -2.55 kcal/mol with cooperativity contribution in the range from 0.02 to -0.61 kcal/mol. The accuracy of these estimated values was validated by adding the sum of interaction energies to the sum of monomer energies. These estimated molecular energies of clusters were compared with their actual calculated values. The small difference (<0.3 kcal/mol) in these two values suggests that our estimated individual intermolecular interaction energies in benzene clusters are quite reliable.

Molecular Tailoring Approach for the Estimation of Intramolecular Hydrogen Bond Energy.

Hydrogen bonds (HBs) play a crucial role in many physicochemical and biological processes. Theoretical methods can reliably estimate the intermolecular HB energies. However, the methods for the quantification of intramolecular HB (IHB) energy available in the literature are mostly empirical or indirect and limited only to evaluating the energy of a single HB. During the past decade, the authors have developed a direct procedure for the IHB energy estimation based on the molecular tailoring approach (MTA), a fragmentation method. This MTA-based method can yield a reliable estimate of individual IHB energy in a system containing multiple H-bonds. After explaining and illustrating the methodology of MTA, we present its use for the IHB energy estimation in molecules and clusters. We also discuss the use of this method by other researchers as a standard, state-of-the-art method for estimating IHB energy as well as those of other noncovalent interactions.

Direct and Reliable Method for Estimating the Hydrogen Bond Energies and Cooperativity in Water Clusters, Wn, n = 3 to 8.

No direct method for estimating the individual O-H···O hydrogen bond (H-bond) energies in water clusters (Wn) exists in the literature. In this work, we propose such a direct method based on the molecular tailoring approach, which also enables the estimation of the cooperativity contributions. The calculated H-bond energies at MP2(full)/aug-cc-pVTZ and CCSD(T)/aug-cc-pVDZ levels for Wn, n = 3 to 8, agree well with one another and fall between 0.3 and 11.6 kcal mol-1 with the cooperativity contributions in the range of -1.2 and 7.0 kcal mol-1. For gauging the accuracy of our H-bond energies for a cluster, the H-bond energy sum is added to the sum of monomer energies, and the results are compared with the respective total energy. These two values agree with each other to within 8.3 mH (∼5 kcal mol-1), testifying the accuracy of our estimated H-bond energies. Further, these H-bond strengths show a good correlation with the respective O-H stretching frequencies and the molecular electron density values at the (3, -1) O-H···O H-bond critical point.

Theoretical prediction of Ni(I)-catalyst for hydrosilylation of pyridine and quinoline.

Catalytic synthesis of dihydropyridine by transition-metal complex is one of the important research targets, recently. Density functional theory calculations here demonstrate that nickel(I) hydride complex (bpy)NiI H (bpy = 2,2'-bipyridine) 1 is a good catalyst for hydrosilylation of both quinoline and pyridine. Two pathways are possible; in path 1, substrate reacts with 1 to form stable intermediate Int1. After that, N3 ─C1 bond of substrate inserts into Ni─H bond of 1 via TS1 to afford N-coordinated 1,2-dihydroquinoline Int2 with the Gibbs activation energy (ΔG°‡ ) of 21.8 kcal mol-1 . Then, Int2 reacts with hydrosilane to form hydrosilane σ-complex Int3; this is named path 1A. In the other route (path 1B), Int1 reacts with phenylsilane in a concerted manner via hydride-shuttle transition state TS2 to afford Int3. In TS2, Si atom takes hypervalent trigonal bipyramidal structure. Formation of hypervalent structure is crucial for stabilization of TS2 (ΔG°‡ = 17.3 kcal mol-1 ). The final step of path 1 is metathesis between Ni─N3 bond of Int3 and Si─H bond of PhSiH3 to afford N-silylated 1,2-dihydroproduct and regenerate 1 (ΔG°‡ = 4.5 kcal mol-1 ). In path 2, 1 reacts with hydrosilane to form Int5, which then forms adduct Int6 with substrate through Si-N interaction between substrate and PhSiH3 . Then, N-silylated 1,2-dihydroproduct is produced via hydride-shuttle transition state TS5 (ΔG°‡ = 18.8 kcal mol-1 ). The absence of N-coordination of substrate to NiI in TS5 is the reason why path 2 is less favorable than path 1B. Quinoline hydrosilylation occurs more easily than pyridine because quinoline has the lowest unoccupied molecular orbital at lower energy than that of pyridine. © 2019 Wiley Periodicals, Inc.

Theoretical Study of Nickel-Catalyzed Selective Alkenylation of Pyridine: Reaction Mechanism and Crucial Roles of Lewis Acid and Ligands in Determining the Selectivity.

Selective alkenylation of pyridine is challenging in synthetic organic chemistry due to the poor reactivity and regioselectivity of the aromatic ring. We theoretically investigated Ni-catalyzed selective alkenylation of pyridine with DFT. The first step is coordination of the pyridine-AlMe3 adduct with the active species Ni(0)(NHC)(C2H2) 1 in an η2-fashion to form an intermediate Int1. After the isomerization of Int1, the oxidative addition of the C-H bond of pyridine across the nickel-acetylene moiety occurs via a transition state TS2 to form a Ni(II)(NHC) pyridyl vinyl intermediate Int3. This oxidative addition is rate-determining. The next step is C-C bond formation between pyridyl and vinyl groups leading to the formation of vinyl-pyridine (P1). One of the points at issue in this type of functionalization is how to control the regioselectivity. With the use of Ni(NHC)/AlMe3 catalyst, the C4- and C3-alkenylated products (ΔG°â§§ = 17.4 and 21.5 kcal mol-1, respectively) are formed preferably to the C2 one (ΔG°â§§ = 22.0 kcal mol-1). The higher selectivity of the C4-alkenylation over the C3 and the C2 ones is attributed to the small steric repulsion between NHC and AlMe3 in the C4-alkenylation. Interestingly, with Ni(P(i-Pr)3)/AlMe3 catalyst, the C2-alkenylation occurs more easily than the C3 and C4 ones. This regioselectivity arises from the smaller steric repulsion induced by P(i-Pr)3 than by bulky NHC. It is notable that AlMe3 accelerates the alkenylation by inducing the strong CT from Ni to pyridine-AlMe3. In the absence of AlMe3, pyridine strongly coordinates with the Ni atom through the N atom, which increases Gibbs activation energy (ΔG°â§§ = ∼27 kcal mol-1) of the C-H bond activation. In other words, AlMe3 plays two important roles, acceleration of the reaction and enhancement of the regioselectivity for the C4-alkenylation.

Structures, stability and hydrogen bonding in inositol conformers.

Various ab initio calculations using the density-functional (DFT), the second order Möller-Plesset perturbation (MP2) and self-consistent reaction field (SCRF) theories were performed on thirteen theoretically possible inositol stereoisomers. Gas phase calculations reveal that the myo- and neo-isomers of inositol (bearing one and two axial hydroxyl groups, respectively) are marginally more stable (by 0.5 kcal mol(-1)) than the all equatorially substituted scyllo-inositol. The calculations when done in different polar solvents show that the scyllo-inositol becomes the most stable inositol isomer, a fact attributed to weaker intramolecular hydrogen bonds. The individual hydrogen bond energy in all the isomers of inositol was also estimated using the molecular tailoring approach (MTA). The calculated hydrogen bond energies in these isomers are in excellent agreement with reported O-H···O hydrogen bond distances and ν(O-H) stretching frequencies. The estimated H-bond energy values suggest that the order of the intramolecular hydrogen bond strength follows: axial-axial > equatorial-axial > axial-equatorial > equatorial-equatorial hydrogen bonds. The intramolecular hydrogen bonds in the scyllo isomer are much weaker than those in other conformers, thus making this isomer more stable in polar solvents.