Investigating Materials that Promote New Organic Methodology and Remediation of Volatile Organic Compounds

The need for environmentally safe reagents for the promotion of organic transformations is critical in order to reduce hazardous waste and byproducts associated with industrial-scale chemical processes. We have developed two practical methods that obviate the need for harsh oxidative and toxic brominating reagents in electrophilic halogenation reactions. In our hands, a catalytic loading of the inexpensive, commercially available V2O5 (~$0.25/g) promotes the bromolactonization of a series of substituted alkenoic acids in isolated yields up to 97% by means of the in situ generation of bromenium (Br+) from bromide (Br−) at room temperature. This process obviates the need for molecular bromine (Br2), known for its potent toxicity and threat to the human nervous system, instead relying on the use of less toxic bromide salts, such as ammonium bromide (NH4Br). The oxidation of halides to halenium equivalents has previously relied on the use of harsh oxidants like lead acetate or Oxone®. The system used by our group is promoted by the mild organic oxidant, urea-hydrogen peroxide (UHP), thereby making this process more environmentally benign. The methodology can be extended to afford high yields of α-brominated β-diketones. Our group’s interest in vanadium catalysis through next turned to an investigation of polyoxometalates. Specifically, highly functional, anionic polyoxovanadates (POVs) developed in the Hwu laboratory posed a particular interest as possible catalysts for organic oxidations. A room temperature oxidation of alcohols using reduced polyoxovanadates Cs5(V14As8O42Cl) (III-2) and Cs11Na3(V15O36Cl)Cl5 (III-3) was explored. The selective oxidation of various substituted secondary benzylic alcohols were promoted in good to quantitative yields using only 2 mol % of catalyst III-2 in the presence of the terminal co-oxidant tert-butyl hydrogen peroxide (t-BuOOH). Further investigation has focused on kinetic studies of the transformation. In a separate focus area, our group, in collaboration with the Alexis laboratory developed the preparation of nanoparticles comprised of a Poly(D,L-lactic acid)-poly(ethylene glycol)-poly(ethyleneimine) (i.e. PDLLA-PEG-PEI) tri-block co-polymer. These nanoparticles are capable of selectively capturing environmental contaminants of broad concern bearing aldehyde and carboxylic acid functional groups in the gas phase. These materials effected greater than 80% and 76% reduction of aldehyde and carboxylic acid vapors, respectively, with reductions of up to 98% in some cases. Further, we demonstrated the functionalization of kaolinite and montmorillonite clays with PEI on a multi-gram scale using wet impregnation preparative methods. The synthesized amino-kaolinite clay revealed significant efficiency in capturing volatile aldehydes, carboxylic acids, and sulfides with most of these assays showing 100% reduction of these vapors. Future studies will focus on similar evaluation of the remediation capabilites, with the MMT and MMT-PEI clay minerals

Recent advances in stereoselective bromofunctionalization of alkenes using N-bromoamide reagents

10.1039/C3CC43950JChemical Communications49737985-799

Applications of enantioselective halolactonization reactions, synthesis of photocaged compounds for identifying neurons based on function, and progress towards the total synthesis of alstoscholarisine E

Recently the Martin group developed a bifunctional organic catalyst that promotes highly efficient enantioselective halolactonization reactions for olefinic acids. Using the BINOL-amidine catalyst we invented, our group was able to perform halolactonization reactions on a broad array of substrates. Herein we describe the synthetic utility of this method through a concise synthesis of (+)-disparlure, along with the preparation of F ring synthons for the natural product kibdelone C. As part of a separate project, in collaboration with the Zemelman research group, we are working to design a system for identifying behaviorally relevant assemblies of neurons in awake animals. This novel technique identifies active neurons and tags them using fluorescent proteins that are expressed upon irradiation of the neuron with visible light. This system hinges on the preparation on light sensitive derivatives of a variety of repressor protein ligands using “cages” or “photocages.” Toward this end, we prepared photocaged derivatives of anhydrotetracycline and vanillic acid. Finally, we disclose our progress towards the total synthesis of alstoscholarisine E, a natural product isolated in 2014 that was found to be a strong promoter of adult neuronal stem cell proliferation. We envisioned a convergent synthesis where skatole and a hetero-Diels-Alder product could be joined through a metal catalyzed coupling to form the tetracyclic core of the molecule, which could then be easily transformed to alstoscholarisine E through an olefin reduction followed by a reductive cyclization. Accessing our desired hetero-Diels-Alder product quickly was paramount to the effectiveness of this route, and thus, we developed a method to access hetero-Diels-Alder precursors in one step starting from readily available hexahydrotriazines.Chemistr

ORGANOCATALYTIC HALOFUNCTIONALIZATION OF OLEFINS

Ph.DDOCTOR OF PHILOSOPH

Organocatalysis [review article]

Reactions carried out with substoichiometric quantities of organic molecules as catalysts have received much attention over the past decade. This review highlights progress in 2011 towards highly enantioselective organocatalytic systems and the natural product/biologically active compounds that can be prepared using these types of processes

2,2\u27,6,6\u27-Tetrasubstituted Diarylethynes: Models to Test Proximity and Position in Catalysis.

Enzymes exhibit extraordinary efficiency and specificity in catalysis. A source of the catalytic power observed in enzymes has been attributed to the ability of the enzyme-substrate complex to bring the substrate into close proximity to the catalytic groups with proper orientation for reaction. However, the contributions of proximity and of orientation to the origin of catalytic power have not been quantified. A series of tethered and untethered 2,2\sp\prime,6,6\sp\prime-tetrasubstituted diarylethynes have been proposed to study the effect of proximity of the catalytic group to the substrate on catalysis. The syntheses of the diarylethyne models require efficient procedures for the synthesis of 2,6-disubstituted arylethynes and unsymmetrical 2,2\sp\prime,6,6\sp\prime-tetrasubstituted diarylethynes. A literature search for the preparation of mono- and diarylethynes has revealed no examples of 2,6-disubstituted arylethynes with oxygen substituents or unsymmetrical 2,2\sp\prime,6,6\sp\prime-tetrasubstituted diarylethynes. The methodology developed for synthesizing these mono- and diarylethynes serves as a basis for synthesizing the models. Two procedures have been developed for the synthesis of arylethynes. The first method involves a modification of a classic procedure for synthesizing arylethynes from acetophenones. The second procedure involves a palladium-mediated coupling of aryl iodides with trimethyl ((trimethylsilyl)ethynyl) stannane, followed by cleaving the trimethylsilyl group. The advantages and disadvantages of these procedures are discussed. Six new arylethynes have been synthesized by these methods. Unsymmetrical diaryl- and arylnaphthylethynes have been synthesized by palladium-mediated coupling of arylethynes with aryl triflates or halides. The arylnaphthylethynes serve as precursors to another series of models, which have different distances and orientations between the functional groups, to test proximity on catalysis. A close precursor to the untethered diarylethyne, 2- (2-methoxy-6-(methoxymethoxy)-phenylethynyl) -3-methoxybenzoate, was synthesized. One pathway for the synthesis of the tethered models has been eliminated; however, three additional pathways are proposed. The ortho-substituted functional groups of the 2,2\sp\prime,6,6\sp\prime-tetrasubstituted diarylethynes react with ethyne to form three heterocycles. The robust chemistry of the demethylation and lactonization of the diarylethynes provides an easy entry to unusual and highly substituted 2-arylbenzofurans, 3-arylbenzopyranones, and 3-benzylideneisobenzofuranones

BINOL-derived bifunctional sulfide catalysts for asymmetric synthesis of 3,3-disubstituted phthalides via bromolactonization

An efficient enantioselective synthesis of 3,3-disubstituted phthalides possessing a chiral quaternary carbon center was achieved via catalytic asymmetric bromolactonization that utilized BINOL-derived bifunctional sulfide catalysts. Transformations of the bromo group in optically active phthalide products were also performed to demonstrate the utility of this novel synthetic protocol

Butenolide Synthesis via Cation-Initiated Ring Expansion/Elimination of β-Lactones

An area of recent research in the Black research group is an exploration of the potential of cation-initiated β-lactone ring expansions, accompanied by the elimination of a proton or other electrofuge, as a protocol for the synthesis of multisubstituted butenolides. Γ-Bromo β-lactones were prepared via bromolactonization of the appropriate β,Γ-unsaturated acids under basic conditions. The nucleofugal bromine atom on the Γ-carbon was then employed to effect carbocation formation adjacent to the lactone ring oxygen atom; the most efficacious reagent combination was found to be silver nitrate in refluxing acetic acid. Generation of this cation initiated a migration of the β-lactone ring oxygen atom to the Γ-position, whereupon loss of the α-proton produced butenolides in 30 to 75% yield. Successful implementation of this conceptually novel strategy will provide a versatile and expedient route for the synthesis of butenolides bearing a wide range of substitution patterns. Cycloaddition of α-trimethylsilylketene (TMS ketene) to aldehydes bearing carbocation progenitors in the α-position provided α-trimethylsilyl β-lactones which were then examined as substrates for the ring expansion/elimination sequence. In contrast to aldehydes, ketones were transformed into α,β-unsaturated acids under the same conditions