Joseph P. Konopelski

Pyrene-Functionalized Ruthenium Nanoparticles as Effective Chemosensors for Nitroaromatic Derivatives

Pyrene-functionalized Ru nanoparticles were synthesized by olefin metathesis reactions of carbene-stabilized Ru nanoparticles with 1-vinylpyrene and 1-allylpyrene (the resulting particles were denoted as Ru=VPy and Ru=APy, respectively) and examined as sensitive chemosensors for the detection of nitroaromatic compounds, such as 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), 1-chloro-nitrobenzene (CNB), and nitrobenzene (NB), by their effective quenching of the nanoparticle fluorescence. It was found that the detection sensitivity increased with increasing nitration of the molecules. Additionally, in comparison to monomeric pyrene derivatives, both Ru=VPy and Ru=APy nanoparticles exhibited markedly enhanced performance in the detection of nitroaromatic explosives, most probably as a result of the enhanced collision frequency between the fluorophores and the quencher molecules. Furthermore, Ru=VPy nanoparticles displayed much higher sensitivity (down to the nanomolar regime for TNT) than Ru=APy in the detection of these nitroaromatic explosives, which was ascribed to the extended intraparticle conjugation that provided efficient pathways for energy/electron transfer and consequently amplified the analyte binding events.

Nanoparticle-Mediated Intervalence Transfer

Nanoparticle-mediated intervalence transfer was reported with ferrocene moieties that were attached onto the ruthenium nanoparticle surface by ruthenium-carbene pi bonds. The resulting particles exhibited two pairs of voltammetric waves with a potential spacing of about 200 mV and a rather intense absorption peak in the near-infrared range (approximately 1930 nm) at mixed valence. Both features suggested Class II characteristics of the intraparticle intervalence transfer that mainly arose from through-bond interactions between the metal centers. Quantum calculations based on density functional theory showed that the nanoparticle core electrons served as conducting band states for the effective charge delocalization between particle-bound ferrocene moieties.

Enantiomerically Pure trans-β-Lactams from α-Amino Acids via Compact Fluorescent Light (CFL) Continuous Flow Photolysis

Photolysis of alpha-diazo-N-methoxy-N-methyl (Weinreb) beta-ketoamides derived from enantiomerically pure (EP) alpha-amino acids affords the corresponding EP beta-lactams via an intramolecular Wolff rearrangement. The photochemistry is promoted with either standard UV irradiation or through the use of a 100 W compact fluorescent light; the latter affords a safe and environmentally friendly alternative to standard photolysis conditions. A continuous-flow photochemical reactor made from inexpensive laboratory equipment reduced reaction times and was amenable to scale-up. The diastereoselectivity (cis or trans) of the product beta-lactams has been shown to vary from modest to nearly complete. An extremely facile, atom-economical method for the epimerization of the product mixture to the trans isomer, which is generally highly crystalline, has been developed. Evidence for C3 epimerization of Weinreb amide structures via a nonbasic, purely thermal route is presented. Subsequent transformations of both the Weinreb amide at C3 (beta-lactam numbering) and the amino acid side chain at C4 are well-tolerated, allowing for a versatile approach to diverse beta-lactam structures. The technology is showcased in the synthesis of a common intermediate used toward several carbapenem-derived structures starting from unfunctionalized aspartic acid.

SELF-REPRODUCTION OF CHIRALITY. ASYMMETRIC SYNTHESIS OF BETA -ARYL-BETA -AMINO ACIDS FROM ENANTIOMERICALLY PURE DIHYDROPYRIMIDINONES

Enantiomerically pure dihydropyrimidinone 1 reacts with aryl iodides in the presence of catalytic amounts of Pd(OAc) 2 and added phosphine to afford dihydropyrimidinone 4, in which a formal conjugate addition of the aryl group to the α,β-unsaturated system has occurred. Application of this methodology to the synthesis of a protected version of the tripeptide portion of the natural product jasplakinolide is presented

Computational study of bridge-assisted intervalence electron transfer.

Intervalence electron transfer reactions were studied computationally by means of density functional theory and constrained density functional theory (CDFT). Two ferrocene moieties, connected via various bridge structures, were used as model mixed-valence compounds in the computational investigation. Features of the frontier orbitals were analyzed to offer a qualitative account of the intervalence characteristics of the model complexes. The effective electronic coupling between the donor and acceptor sites was calculated using the CDFT method, which provided a quantitative measure of the intervalence electronic communication. The relationship between the bridge linkage and the effectiveness of intervalence transfer was discussed on the basis of the theoretical results and compared to experimental data available in the literature.

Alkyne-Stabilized Ruthenium Nanoparticles: Manipulation of Intraparticle Charge Delocalization by Nanoparticle Charge States†

Monolayer-protected transition metal nanoparticles are a unique family of functional nanomaterials in which the properties of the materials can be readily manipulated not only by the chemical nature of the metal cores and the organic protecting ligands, but also the metal–ligand interfacial bonding interactions. The latter is largely motivated by recent progress in nanoparticle passivation by metal–carbon covalent bonds, where intraparticle charge delocalization may occur as a result of the strong metal–carbon interfacial bonding interactions, in sharp contrast to nanoparticles that are functionalized by mercapto derivatives. For instance, when ferrocene moieties are bound onto a ruthenium nanoparticle surface by ruthenium–carbene p bonds, effective intervalence transfer occurs between the ferrocenyl metal centers at mixed valence, as manifested in electrochemical and near-infrared (NIR) spectroscopic measurements and density functional calculations. Furthermore, when fluorophores are attached onto the nanoparticle surface by the same conjugated linkage, novel emission characteristics emerge that are consistent with those of dimeric derivatives with a conjugated spacer. In a more recent study, effective intraparticle charge delocalization was also observed with ruthenium nanoparticles passivated by alkynyl fragments. This result was ascribed to the unique interfacial bonding interactions (Ru C ) formed by ruthenium and sphybridized carbon atoms of the ligands. In these studies, the nanoparticle metal cores serve as the conducting media to facilitate charge transfer between the functional moieties covalently bound onto the nanoparticle surface. Therefore it is anticipated that the extent of intraparticle conjugation may be readily controlled by the nanoparticle charge state, which is the primary motivation of the present study. Experimentally, by exploiting the molecular capacitor characters of Ru C nanoparticles, the charge states of the nanoparticles were varied by simple chemical reduction or oxidation. The impacts of the nanoparticle charge states on the particle optical and electronic properties were then carefully examined by FTIR spectroscopy, X-ray photoelectron spectroscopy (XPS), and photoluminescence measurements, and compared to those of the as-prepared nanoparticles. The synthetic procedure for the preparation of ruthenium nanoparticles passivated by 1-octynyl fragments (Ru-OC) has been detailed previously. TEM measurements showed that the nanoparticles exhibited an average core diameter of (2.55 0.15) nm. The nanoparticle charge states were then varied by chemical redox reactions. Specifically, to render the nanoparticles negatively charged, in a typical reaction, 5 mg of Ru-OC nanoparticles were dissolved in dichloromethane (1 mL); a freshly prepared water solution of NaBH4 (1 mL, 5 mgmL ) was then added. The mixture was stirred for 30 min and then water was removed. The resulting nanoparticles exhibited negative net charges and were denoted as Ru-OCRed. Positively charged nanoparticles were prepared in a similar fashion by mixing the nanoparticle solution with an aqueous solution of saturated Ce(SO4)2 for 30 min. The resulting nanoparticles were denoted as Ru-OCOx. Transition metal nanoparticles passivated with a lowdielectric organic protecting layer have long been known to act as nanoscale molecular capacitors. In fact, based on a concentric structural model, the nanoparticle capacitance (CMPC) can be estimated by CMPC= 4pe0e(r+d) r d, where e0 is the vacuum permittivity, e is the effective dielectric constant of the organic protecting layer, r is the radius of the metal core, and d is the length of the organic protecting ligand. For the octyne-passivated ruthenium (Ru-OC) nanoparticles, r= 1.275 nm, d= 0.848 nm (estimated by Hyperchem), and e= 2.6. Thus, the nanoparticle capacitance can be estimated to be about 0.92 aF. To quantify the change of the nanoparticle charge state after reduction or oxidation, we measured the open circuit potentials of the nanoparticles electrochemically. It was found that the as-prepared Ru-OC nanoparticles exhibited an open circuit potential of + 0.140 V (versus Ag/AgCl). After reduction by NaBH4, it decreased to + 0.024 V, whereas after oxidation by ceric sulfate, it increased to + 0.250 V. This result indicated that the reduced nanoparticles (Ru-OCRed) exhibited an average charging of 0.67 electrons per nanoparticle, whereas the oxidized nanoparticles (Ru-OCOx) were formed by an average discharging of 0.63 electrons per nanoparticle. Interestingly, despite these subtle changes of nanoparticle charge states, rather drastic impacts were observed on the nanoparticle optoelectronic properties. Figure 1 depicts the FTIR spectra of the nanoparticles before and after reduction or oxidation. For the as-prepared Ru-OC nanoparticles, the C C stretching band appeared at 1965 cm 1 (inset). In comparison to octyne monomers, for which the C C stretch[*] X. W. Kang, N. B. Zuckerman, Prof. J. P. Konopelski, Prof. S. W. Chen Department of Chemistry and Biochemistry, University of California 1156 High Street, Santa Cruz, CA 95064 (USA) Fax: (+1)831-459-2935 E-mail: shaowei@ucsc.edu Homepage: http://chemistry.ucsc.edu/~ schen

Progress toward the Total Synthesis of Psymberin/Irciniastatin A

In this paper, we describe our synthesis of four key building blocks for the total synthesis of psymberin (1) and its C4 epimer (2). Despite early difficulties in processing material to the advanced intermediate stage, we have been successful in developing high-yielding syntheses for the pyran core, natural side chain, 4-epi side chain, and aryl fragments of the molecule. Our findings from the optimization process are presented herein.

TURNING THE CORNER: RECENT ADVANCES IN THE SYNTHESIS OF THE WELWITINDOLINONES

INTRODUCTION ...................................................................................................................... 413 I . RECENT ADVANCES IN THE SYNTHESIS OF WELWITINDOLINONE C ISOTHIOCYANATE .......................................................... 415 2 . Building the Skeletonfrom an Zndole Scaffold (Shea’s Approach) .......................... 416 2 . Seven-membered Macrocyclic Closure ........................................................................ 417 a) Simpkins’ Approach ................................................................................................. 417 b) Rawal’s Approach .................................................................................................... 419 3 . Late Stage Indole Annelation (Funk’s Approach) ...................................................... 421 I1 . TOTAL SYNTHESES OF WELWITINDOLINONE A ISONITRILE ........................ 426 1 . Wood’s Synthesis ........................................................................................................... 426 2 . Baran’s Synthesis ........................................................................................................... 431 I11 . CONCLUSION .................................................................................................................... 438 APPENDIX A .............................................................................................................................. 438 APPENDIX B .............................................................................................................................. 440 ACKNOWLEDGEMENTS ....................................................................................................... 442 REFERENCES ........................................................................................................................... 442

Acylketene acetals in organic synthesis.

Abstract The preparation and reactivity of achiral and enantiomerically pure acylketene acetals are described. The key reactions of these substrates involve facile conjugate hydroboration and organolithium addition. Enantiomerically pure acylketene acetals were employed to generate a homochiral β-keto ketal through a highly diastereoselective lithium enolate quench. This β-keto ketal, which was also prepared through a desymmetrization ketalization reaction on a meso dione, was employed in the synthesis of the insect pheromone sitophilure.

ASYMMETRIC ALKYLATIONS OF N-ACYL DIHYDROPYRIMIDINONES

Abstract Enantiomerically pure dihydropyrimidin-4-one 1 has been employed as a chiral auxiliary for enantioselective alkylation reactions. Acylation of 1 , followed by enolate formation, alkylation and acyl cleavage, affords α-alkylated carboxylic acids in high chemical yield and enatiomeric purity.