Mariappan Manoharan

Dissected Nucleus-Independent Chemical Shift Analysis of π-Aromaticity and Antiaromaticity

Analysis of the basic π-aromatic (benzene) and antiaromatic (cyclobutadiene) systems by dissected nucleus-independent chemical shifts (NICS) shows the contrasting diatropic and paratropic effects, but also reveals subtleties and unexpected details.

Radical cascade transformations of tris(o-aryleneethynylenes) into substituted benzo[a]indeno[2,1-c]fluorenes.

Oligomeric o-aryleneethynylenes with three triple bonds undergo cascade radical transformations in reaction with a Bu 3SnH/AIBN system. These cascades involve three consecutive cycle closures with the formation of substituted benzo[ a]indeno[2,1- c]fluorene or benzo[1,2]fluoreno[4,3- b]silole derivatives. The success of this sequence depends on regioselectivity of the initial attack of the Bu 3Sn radical at the central triple bond of the o-aryleneethynylene moiety. The cascade is propagated through the sequence of 5-exo-dig and 6-exo-dig cyclizations which is followed by either a radical attack at the terminal Ar substituent or radical transposition which involves H-abstraction from the terminal TMS group and 5-endo-trig cyclization. Overall, the transformation has potential to be developed into an approach to a new type of graphite ribbons.

Rehybridization as a general mechanism for maximizing chemical and supramolecular bonding and a driving force for chemical reactions

Dynamic variations in hybridization patterns (rehybridization) were analyzed at B3LYP/6–31G** and MP2/6–31+G* levels. Computations clearly illustrate the generality of rehybridization in a variety of chemical phenomena, which involve structural reorganization in hydrogen‐bonded complexes, nonhyperconjugative stereoelectronic effects in saturated heterocycles, Mills‐Nixon effect, and contrasting substituent effects in cycloaromatization reactions.

In Search of Efficient 5-Endo-dig Cyclization of a Carbon-Centered Radical: 40 Years from a Prediction to Another Success for the Baldwin Rules

Despite being predicted to be stereoelectronically favorable by the Baldwin rules, efficient formation of a C-C bond through a 5-endo-dig radical cyclization remained unknown for more than 40 years. This work reports a remarkable increase in the efficiency of this process upon beta-Ts substitution, which led to the development of an expedient approach to densely functionalized cyclic 1,3-dienes. Good qualitative agreement between the increased efficiency and stereoselectivity for the 5-endo-dig cyclization of Ts-substituted vinyl radicals and the results of density functional theory analysis further confirms the utility of computational methods in the design of new radical processes. Although reactions of Br atoms generated through photochemical Ts-Br bond homolysis lead to the formation of cyclic dibromide side products, the yields of target bromosulfones in the photochemically induced reactions can be increased by recycling the dibromide byproduct into the target bromosulfones through a sequence of addition/elimination reactions at the exocyclic double bond. Discovery of a relatively efficient radical 5-endo-dig closure, accompanied by a C-C bond formation, provides further support to stereoelectronic considerations at the heart of the Baldwin rules and fills one of the last remaining gaps in the arsenal of radical cyclizations.

Direct Observation of the Ion-Pair Dynamics at a Protein–DNA Interface by NMR Spectroscopy

Ion pairing is one of the most fundamental chemical interactions and is essential for molecular recognition by biological macromolecules. From an experimental standpoint, very little is known to date about ion-pair dynamics in biological macromolecular systems. Absorption, infrared, and Raman spectroscopic methods were previously used to characterize dynamic properties of ion pairs, but these methods can be applied only to small compounds. Here, using NMR (15)N relaxation and hydrogen-bond scalar (15)N-(31)P J-couplings ((h3)J(NP)), we have investigated the dynamics of the ion pairs between lysine side-chain NH3(+) amino groups and DNA phosphate groups at the molecular interface of the HoxD9 homeodomain-DNA complex. We have determined the order parameters and the correlation times for C-N bond rotation and reorientation of the lysine NH3(+) groups. Our data indicate that the NH3(+) groups in the intermolecular ion pairs are highly dynamic at the protein-DNA interface, which should lower the entropic costs for protein-DNA association. Judging from the C-N bond-rotation correlation times along with experimental and quantum-chemically derived (h3)J(NP) hydrogen-bond scalar couplings, it seems that breakage of hydrogen bonds in the ion pairs occurs on a sub-nanosecond time scale. Interestingly, the oxygen-to-sulfur substitution in a DNA phosphate group was found to enhance the mobility of the NH3(+) group in the intermolecular ion pair. This can partially account for the affinity enhancement of the protein-DNA association by the oxygen-to-sulfur substitution, which is a previously observed but poorly understood phenomenon.

Hybridization trends for main group elements and expanding the Bent's rule beyond carbon: more than electronegativity.

Trends in hybridization were systematically analyzed through the combination of DFT calculations with NBO analysis for the five elements X (X = B, C, N, O, and F) in 75 HnX-YHm compounds, where Y spans the groups 13-17 of the periods 2-4. This set of substrates probes the flexibility of the hybridization at five atoms X through variations in electronegativity, polarizability, and orbital size of Y. The results illustrate the scope and limitations of the Bents rule, the classic correlation between electronegativity and hybridization, commonly used in analyzing structural effects in carbon compounds. The rehybridization effects are larger for fluorine- and oxygen-bonds than they are in the similar bonds to carbon. For bonds with the larger elements Y of the lower periods, trends in orbital hybridization depend strongly on both electronegativity and orbital size. For charged species, the effects of substituent orbital size in the more polarizable bonds to heavier elements show a particularly strong response to the charge introduction at the central atom. In the final section, we provide an example of the interplay between hybridization effects with molecular structure and reactivity. In particular, the ability to change hybridization without changes in polarization provides an alternative way to control structure and reactivity, as illustrated by the strong correlation of strain in monosubstituted cyclopropanes with hybridization in the bond to the substituent.

Drawing from a Pool of Radicals for the Design of Selective Enyne Cyclizations

Despite the possibility of intermolecular attack at four different locations, the Bu3Sn-mediated radical cyclization of aromatic enynes is surprisingly selective. The observed reaction path originates from the least stable of the equilibrating pool of isomeric radicals produced by intermolecular Bu3Sn attack at the π-bonds of substrates. The radical pool components are kinetically self-sorted via 5-exo-trig closure, the fastest of the four possible cyclizations. The resulting Sn-substituted indenes are capable of further transformations in reactions with electrophiles.

Fast Oxy-Cope Rearrangements of Bis-alkynes: Competition with Central C-C Bond Fragmentation and Incorporation in Tunable Cascades Diverging from a Common Bis-allenic Intermediate

Fast anionic oxy-Cope rearrangements of 1,5-hexadiyn-3,4-olates can be incorporated into cascade transformations which rapidly assemble densely functionalized cyclobutenes or cyclopentenones via a common bis-allenic intermediate. The competition between fragmentation, 4π-electrocyclic closure, and aldol condensation can be efficiently controlled by the nature of the acetylenic substituents. The rearrangement of bis-alkynes with two hydroxyl substituents opens a conceptually interesting entry in the chemistry of ε-dicarbonyl compounds and suggests a new approach to analogues of rocaglamide/aglafolin.

Cycloaromatization reactions: the testing ground for theory and experiment

Publisher Summary This chapter describes the testing ground for the theory and experiment for cycloaromatization reactions. An interesting breakdown of the tendency for the conservation of chemical bonds occurs in the so-called cycloaromatization reactions. In these reactions, a σ-bond is formed at the expense of two π-bonds, and thus, the process leads to a net loss of one chemical bond that is intrinsically unfavorable thermodynamically. The role of electron repulsion relative to bond breaking and antiaromaticity effects on a quantitative basis using Natural Bond Orbital (NBO) analysis has been recently analyzed. In the case of the Bergman cyclization and the C1–C5 cyclization of enediynes, both the activation barrier for cyclization as well as the thermodynamics of the reaction became more favorable upon one-electron reduction compared to the thermal counterparts. Even though some of the general factors controlling the Bergman cyclization are applicable to newly discovered cycloaromatization reactions, new phenomena such as communication of orthogonal orbitals in radical-anionic, radical-cationic and dianionic cycloaromatizaton, and cyclorearomatization will continue to stimulate future development of this interesting field.

ALLENE AND FLUOROALLENES AS DIENOPHILES IN DIELS-ALDER REACTIONS : AN AM1 AND PM3 STUDY

Transition structures and energetics of Diels–Alder reactions of allene with cyclopentadiene and hexachlorocyclopentadiene, and fluoroallenes with cyclopentadiene and furan have been investigated using semiempirical MO methods at AM1 and PM3 levels. Allene and fluoroallenes react through an asynchronous transition structure in which the terminal carbon atom involved in the reaction pyramidalizes and the central carbon atom triangulates and this deformation accounts for almost half the reaction barrier. Allene is found to be a less reactive dienophile compared to ethylene, contrary to expectations, and its reactivity enhances with fluorine substitution up to 1,1-difluoroallene and declines on further substitution of fluorine. Tetrachloroallene is found to be less reactive than allene itself. The reactivity of furan in such cumulene reactions is found to be almost the same as that of cyclopentadiene. While PM3 predictions in certain cases are not reliable AM1 reaction barriers explain reasonably the reactivities and stereochemical preferences of the above reactions.