PubMed Health⌕ Search

Biomedical subjects

Howard E Zimmerman

Publications and source records attributed to Howard E Zimmerman.

13 recordsLinked to original sources
PubMed2006

Conical intersection control of heterocyclic photochemical bond scission.

The photochemistry of the heterocycle 5,6-dihydro-1-methyl-5,5-diphenylpyridin-2(1H)-one (compound 1 in the text) leads to two competitive reactions (the reactions are depicted in the Introduction to the article). These arise from fission of bond a, between the nitrogen (N-6) and C-1, and bond b, between C-4, with the two phenyl substituents, and C-5, adjacent to the nitrogen. Scission of bond a alone leads to a zwitterionic intermediate which can be trapped by nucleophiles, while cleavage of bonds a and b together affords two fragments--a ketene and an imine. The ketene could be intercepted with nucleophiles and the imine trimerized. Computation reveals little weakening of bonds a and b. But as stretching begins, conical intersections are encountered, leading to ground-state products.

Journal Article↗
PubMed2006

Control of stereoselective protonation of enols1,2.

A decalyl framework with a siloxy enolic moiety and proximate proton transferring groups was synthesized. On enolate generation with fluoride two competitive reaction modes were possible: (a) intermolecular protonation, and (b) intramolecular proton transfer by the proximate group. Control of the protonation stereochemistry proved possible by varying the proximate group and by changing the acidity of the medium. With the groups -CH2OH, -CH=O, and -CH2OCH2OCH3 as the proximate groups, only intermolecular proton transfer was observed with no dependence on acidity. In contrast, with -COO- and COOH, only intramolecular protonation resulted but again with no dependence on acidity of the medium. In contrast, with -CH2NH2 as the proximate group, intramolecular proton transfer predominated with a dependence on the effective pH of the medium. A kinetic analysis provided a linear-log relationship of the ratio of the two stereoisomers with the medium acidity. The analysis revealed that two acetic acid molecules are involved in providing the proton to the enolate moiety. A theoretical analysis was developed paralleling the experimental results. In the ketonization transition state, the hybridization was shown to be close to sp2 hybridized at the alpha-enolate carbon.

Acetic Acid↗
PubMed2005

Control of proton transfer: intramolecular vs intermolecular.

[reaction: see text] Proton transfer in ketonization of enolates is a critical step in a myriad of organic reactions. Its stereochemistry has been the object of our studies since we reported kinetic protonation from the less hindered face of the molecule under kinetic control some decades ago. Very recently, we have succeeded in reversing the stereochemistry using 2-pyridyl groups to deliver the proton. We now report intramolecular delivery by other moieties and control of intramolecular versus intermolecular proton delivery.

Journal Article↗
PubMed2003

The alpha-effect in the stereochemistry of kinetic ketonization of enols.

Kinetic control of the stereoselectivity of protonation of enolates and other strongly delocalized anionic species is involved in a large number of organic reactions. Protonation occurring from the less hindered side of the, e.g., enolic system affords the less stable of two diastereomers. However, one apparent discrepancy has been in the synthesis of prostaglandins. The present research deals with the source of this behavior. A curious effect of the substituent at the enolic alpha carbon was uncovered. In certain instances an alpha substituent is forced to twist into a conformation blocking the proton donor from its side, thus reversing the stereochemistry of protonation. In the course of this research, a number of five-ring enols of varying structure were investigated. Finally, the ketonization reaction course has been studied theoretically.

Journal Article↗
PubMed2003

Regioselectivity of the tri-pi-methane rearrangement: mechanistic and exploratory organic photochemistry.

The di-pi-methane rearrangement with two pi-groups attached to the central "methane carbon" of the reactant and which leads to a pi-substituted cyclopropane has been studied intensively. Our present research had the goal of elucidating the regioselectivity of the tri-pi-methane counterpart. The reactants with three pi groups attached to the central carbon mechanistically are capable of affording both di-pi-methane and tri-pi-methane photoproducts. In common with the di-pi-methane system, bridging of two of the pi-systems affords a cyclopropyldicarbinyl diradical intermediate that opens to an allyl carbinyl diradical. This diradical has the option of closing to a three-membered or a five-membered ring. It was found that the regioselectivity of the initial pi-pi-bridging step and the three-ring opening of the cyclopropyldicarbinyl diradical exhibit regioselectivity parallel to that of the di-pi counterpart. Both three-ring and five-ring photoproducts were formed with the ratio varying with conversion. Since the three-ring (i.e. di-pi-methane) photoproducts were found to ring expand to the five-ring (i.e. tri-pi-methane) products, kinetics were employed to determine to what extent the reaction proceeds in a two-step versus direct formation of the five-ring product. It was found that the direct route was the major one.

Journal Article↗
PubMed2003

An experimental and theoretical study of the type C enone rearrangement: mechanistic and exploratory organic photochemistry.

We recently described a new photochemical rearrangement which we termed a Type C process. The reaction involves a delta to alpha aryl migration in 5-disubstituted cyclohexenones also having bulky C-3 substituents. In contrast to most cyclohexenone rearrangements, the reaction occurs via a twisted pi-pi excited triplet rather than the usual n-pi state. The electronic nature of the rearrangement was assessed using migration selectivity with p-anisyl and p-cyanophenyl groups. A synthesis of the reactants was elaborated, and the product structures were established by X-ray and NMR analysis. The reaction mechanism was established further with DFT and CASSCF computations. In the latter, localized NBO basis orbitals permitted proper selection of the active space. The nature of the diradical intermediates as well as the transition states was established computationally. Sensitization experiments with regioselectivities the same as those in direct irradiation confirmed the triplet multiplicity of the process.

Journal Article↗
PubMed2003

Solution and crystal lattice effects on the photochemistry of 6-substituted cyclohexenones(1)(,)(2).

The photochemistry of 13 4,4-diphenylcyclohexenones, substituted at carbon-6, was investigated in solution and in the crystalline state. The stereoselectivity was of particular interest. In the solution photochemistry of C-6 monosubstituted enones in benzene, there was a unique preference for migration of the cis-phenyl group with formation of bicyclo[3.1.0]hexanone photoproducts, with the original 6-substituent having an endo configuration at carbon-3 of the product. In methanol the reaction was diverted to afford 3,4-diphenylcyclohex-2-enes understood as arising from a hydrogen-bonded zwitterionic intermediate. The solid-state photochemistry was also investigated. There was a dramatic absence of the 3,4-diphenylcyclohex-2-ene products in accord with the absence of the hydrogen bonding encountered in methanol. Further, the solid-state reactivity correlated with a vector analysis using X-ray atomic coordinates. This established that the migrating phenyl group required an orientation facing the enone beta-carbon. While the interesting preference for the cis-endo migration was not intuitively predicted, ab initio computations on the alternative phenyl-bridged triplet intermediates did lead to an understanding of the selectivity.

Journal Article↗
PubMed2002

Inter- and intramolecular stereoselective protonation of enols(1,2).

Kinetic control of the stereoselectivity of protonation of enolates and other delocalized species commonly affords the less stable diastereomer as a consequence of the considerable exothermicity and resulting sp(2) transition-state hybridization of the alpha-carbon. Protonation then is from the less hindered face of the enolate. The present study is aimed at reversing this phenomenon by intramolecular delivery of the proton. The approach employed required the synthesis of two enolate precursors, one with a 2-pyridyl group strategically close to the alpha-carbon and the other with a phenyl group in the same location. The synthesis required 15 steps and involved new methodology. Intramolecular proton transfer, reversing the usual stereoselectivity, was successful. The selectivity proved to depend on several factors including the exo versus endo configuration of the diastereomer reacting, the proton donor employed, and the concentration of the proton donor. A kinetic analysis permitted the determination of the relative reaction orders of the protonation on the two faces of the enolate.

Journal Article↗
PubMed2002

Intramolecular proton transfer.

[structure: see text] Reversal of the normal kinetic protonation stereochemistry results as a consequence of intramolecular delivery.

Journal Article↗
PubMed2002

Quantitative cavities and reactivity in stages of crystal lattices: mechanistic and exploratory organic photochemistry.

In continuing our research on solid-state organic photochemistry, we have been investigating the phenomenon of reactivity in stages. In this study we present new examples where the photochemical reactivity changes discontinuously at some point in the conversion. In these instances, the reaction course of the solid differs from that in solution. One example is the reaction of 2-methyl-4,4-diphenylcyclohexenone, where an unusual reaction course was encountered in the solid state; and, of two possible mechanisms, one was established by isotopic labeling. A second case is that of 4,5,5-triphenylcyclohexenone. The solid-state reaction of this enone was found to give a new photochemical transformation, the Type C rearrangement, a process that involves a delta to alpha aryl migration. In the case of 3-tert-butyl-5,5-diphenylcyclohexenone the Type C rearrangement occurred even in solution. The stage behavior was investigated using X-ray analysis and Quantum Mechanics/Molecular Mechanics computations. This permitted us to determine the sources and details of the stage phenomenon. The analysis revealed how a product molecule as a neighbor affects reactivity. The computations were employed to follow the course of a solid-state reaction from reactant through the succeeding stages. Additionally, the Delta-Density Analysis was utilized to ascertain the electronic nature of molecular changes. Besides product composition changing with extent of conversion, the reaction quantum yield was found to change as one stage gave way to a succeeding one.

Journal Article↗
PubMed2002

Development of experimental and theoretical crystal lattice organic photochemistry: the quantitative cavity. Mechanistic and exploratory organic photochemistry.

The photochemistry of organic reactants in the crystalline state has a long history. What has been lacking is comprehensive theory defining what controls the course of these reactions which quite often afford products not obtainable in solution. Also lacking has been solid-state rearrangement chemistry with accompanying theory. In our research over the past two decades we have developed theoretical treatments of solid-state reactivity. This report describes the development of this research from its primitive beginnings to the present.

Journal Article↗