The mechanism of the rhodium(I)-catalyzed [2 + 2 + 1] carbocyclization reaction of dienes and CO: a computational study.

The rhodium(I) catalyzed [2 + 2 + 1] carbocyclization of tethered diene-enes to afford substituted hexahydropentalenones with high levels of diastereoselectivity was modeled using density functional theory. Previously, this transformation was observed to be facile, whereas the analogous bis-ene substrate could not be cyclized under any reasonable conditions. To establish a conceptual understanding of the carbocyclization mechanism and to identify the functional role of the diene fragment we analyzed the simulated reaction mechanisms using the two parent systems. We discovered a thus far unrecognized, but intuitively plausible, role of the CO ligand for controlling the electron density at the metal center, which affects the feasibility of oxidative addition and reductive elimination steps that are key components of the mechanism. Our calculations suggest that the diene moiety is unique and required because of its ability to undergo a eta(2)-->eta(4) reorganization allowing for the thermoneutral expulsion of one CO ligand, which in turn generates an electron-rich, coordinatively saturated Rh(I) center that can efficiently promote the oxidative addition with a low barrier. A number of functionalization strategies were considered explicitly to derive a rational plan for optimizing the catalysis and to expose the roles of the different components of the reactant-catalyst complex.

Studies of the generation and pericyclic behavior of cyclic pentadienyl carbanions. Alkylation reactions as an efficient route to functionalized cis-bicyclo[3.3.0]octenes.

Carbolithiation has been studied with alkyllithium reagents in a series of six- through nine-membered 3-methylene-1,4-cycloalkadienes, efficiently producing the corresponding cyclic pentadienyl carbanions. These pentadienyl anions display unique reactivity, depending on ring size. Cyclooctadienyl anions readily undergo disrotatory electrocyclization to cis-bicyclo[3.3.0]octenyl systems, which are trapped with a variety of electrophiles to stereoselectively provide functionalized cis-bicyclo[3.3.0]octenes. The carbolithiation and electrocyclization processes are examined using low-temperature (1)H NMR experiments. An expedient synthesis of a linear triquinane illustrates this methodology. Electrocyclization of the corresponding cyclononadienyl anion requires unusually high temperatures (120 degrees C), and computational studies provide insights into this change in reactivity. Cycloheptadienyl and cyclohexadienyl anions, generated via carbolithiation, provide functionalized cycloheptadienes and cyclohexadienes upon electrophilic capture. Trapping experiments reveal that the cycloheptadienyl anions are transformed to heptatrienyl anions. A series of experiments have been designed to explore evidence for the feasibility of equilibration of open and closed anionic systems, and these studies report the first isolation of a cis-bicyclo[3.1.0]hexene derived from electrocyclization of a cyclohexadienyl carbanion.

Direct nitric oxide detection in aqueous solution by copper(II) fluorescein complexes.

A series of FL(n) (n = 1-5) ligands, where FL(n) is a fluorescein modified with a functionalized 8-aminoquinoline group as a copper-binding moiety, were synthesized, and the chemical and photophysical properties of the free ligands and their copper complexes were investigated. UV-visible spectroscopy revealed a 1:1 binding stoichiometry for the Cu(II) complexes of FL(1), FL(3), and FL(5) in pH 7.0 buffered aqueous solutions. The reactions of FL(2) or FL(4) with CuCl(2), however, appear to produce a mixture of 1:1 and 1:2 complexes, as suggested by Job's plots. These binding modes were modeled by the synthesis and X-ray crystal structure determination of Cu(II) complexes of 2-[(quinolin-8-ylamino)methyl]phenol (modL), employed as a surrogate of the FL(n) ligand family. Two kinds of crystals, [Cu(modL)(2)](BF(4))(2) and [Cu(2)(modL')(2)(CH(3)OH)](BF(4))(2) (modL' = 2-[(quinolin-8-ylamino)methyl]phenolate), were obtained. The structures suggest that one oxygen and two nitrogen atoms of the FL(n) ligands most likely bind to Cu(II). Introduction of nitric oxide (NO) to pH 7.0 buffered aqueous solutions of Cu(FL(n)) (1 microM CuCl(2) and 1 microM FL(n)) at 37 degrees C induces an increase in fluorescence. The fluorescence response of Cu(FL(n)) to NO is direct and specific, which is a significant improvement over commercially available small molecule-based probes that are capable of detecting NO only indirectly. The NO-triggered fluorescence increase of Cu(FL(5)) occurs by reduction of Cu(II) to Cu(I) with concomitant dissociation of the N-nitrosated fluorophore ligand from copper. Spectroscopic and product analyses of the reaction of the FL(5) copper complex with NO indicated that the N-nitrosated fluorescein ligand (FL(5)-NO) is the species responsible for fluorescence turn-on. Density functional theory (DFT) calculations of FL(5) versus FL(5)-NO reveal how N-nitrosation of the fluorophore ligand brings about the fluorescence increase. The copper-based probes described in the present work form the basis for real-time detection of nitric oxide production in living cells.

Regioselective organocadmium alkylations of substituted quinones.

A series of substituted quinones was alkylated with diethylcadmium. Regiochemistry of addition shifted from quinol formation to conjugate addition as a function of the steric and electronic effects of the substituents.