PUBLICATIONS
An overview of my published research
Every project I've worked on came with both unforeseeable challenges and opportunities. The publications that arose from these challenges were the result of great teams, collaborators, and scientific rigor. I'm truly grateful to have worked with so many dedicated people from whom I'm learned so much.
DIRECT LEWIS ACID CATALYZED CONVERSION OF ENANTIOENRICHED N-ACYLOXAZOLIDINONES TO CHIRAL ESTERS, AMIDES, AND ACIDS
November 19, 2018
The identification of Yb(OTf)3 through a multivariable high-throughput experimentation strategy has enabled a unified protocol for the direct conversion of enantioenriched N-acyloxazolidinones to the corresponding chiral esters, amides, and carboxylic acids. This straightforward and catalytic method has shown remarkable chemoselectivity for substitution at the acyclic N-acyl carbonyl for a diverse array of N-acyloxazolidinone substrates. The ionic radius of the Lewis acid catalyst was demonstrated as a key driver of catalyst performance that led to the identification of a robust and scalable esterification of a pharmaceutical intermediate using catalytic Y(OTf)3.
UTILIZING NATIVE DIRECTING GROUPS: SYNTHESIS OF A SELECTIVE IKUR INHIBITOR, BMS-919373, VIA A REGIOSELECTIVE C–H ARYLATION
November 5, 2018
BMS-919373 is a highly functionalized quinazoline under investigation as a selective, potent IKurcurrent blocker. By utilizing the aminomethylpyridine side chain at C-4, a selective C–H functionalization at C-5 was invented, enabling the efficient synthesis of this molecule. The strategy of leveraging this inherent directing group allowed the synthesis of this complex heterocycle in only six steps from commodity chemicals. The scope of the C–H activation was further investigated, and the generality of the transformation across a series of bicyclic aromatic heterocycles was explored.
ADVANCES IN BASE-METAL CATALYSIS: DEVELOPMENT OF A SCREENING PLATFORM FOR NICKEL-CATALYZED BORYLATIONS OF ARYL (PSEUDO)HALIDES WITH B2(OH)4
August 14, 2018
Investigations into nickel-catalyzed borylation reactions have led to the development of an experimental design of 24 reaction conditions for rapid lead identification. A case study on the borylation of a model aryl bromide with B2(OH)4 prompted a series of mechanistic and stability studies to better understand the catalytic cycle and factors that affect robustness. HTEx was employed to study the effect of a series of scavengers on the remediation of nickel from the reaction stream. These combined results have generated an increased understanding of nickel-catalyzed borylation reactions and set the stage for their expanded use in process chemistry.
TCFH–NMI: DIRECT ACCESS TO N-ACYL IMIDAZOLIUMS FOR CHALLENGING AMIDE BOND FORMATIONS
June 29, 2018
Challenging couplings of hindered carboxylic acids with non-nucleophilic amines to form amide bonds can be accomplished in high yields, and in many cases, with complete retention of the adjacent stereogenic centers using the combination of N,N,N′,N′-tetramethylchloroformamidinium hexafluorophosphate (TCFH) and N-methylimidazole (NMI). This method allows for in situgeneration of highly reactive acyl imidazolium ions, which have been demonstrated to be intermediates in the reaction. The reagent delivers high reactivity similar to acid chlorides with the ease of use of modern uronium reagents.
ADVENTURES IN ATROPISOMERISM: TOTAL SYNTHESIS OF A COMPLEX ACTIVE PHARMACEUTICAL INGREDIENT WITH TWO CHIRALITY AXES
June 17, 2018
A strategy to prepare compounds with multiple chirality axes, which has led to a concise total synthesis of compound 1A with complete stereocontrol, is reported.
CITU: A PEPTIDE AND DECARBOXYLATIVE COUPLING REAGENT
November 08, 2017
Tetrachloro-N-hydroxyphthalimide tetramethyluronium hexafluorophosphate (CITU) is disclosed as a convenient and economical reagent for both acylation and decarboxylative cross-coupling chemistries. Within the former set of reactions, CITU displays reactivity similar to that of common coupling reagents, but with increased safety and reduced cost. Within the latter, increased yields, more rapid conversion, and a simplified procedure are possible across a range of reported decarboxylative transformations.
IMPROVING ROBUSTNESS: IN SITU GENERATION OF A PD(0) CATALYST FOR THE CYANATION OF ARYL BROMIDES
June 8, 2017
Conditions have been developed for the palladium-catalyzed cyanation of aryl bromides utilizing the air-stable XantPhos-PdCl2 precatalyst. By employing a trialkylamine as a reducing agent, the active Pd(0) species is generated in situ, alleviating the need to employ the air-sensitive Pd2(dba)3. Twenty-two substituted benzonitriles have been synthesized using this method.
ANNUAL REVIEW OF CHEMICAL AND BIOMOLECULAR ENGINEERING
January 20, 2017
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ENANTIOSELECTIVE Α-ALKENYLATION OF ALDEHYDES WITH BORONIC ACIDS VIA THE SYNERGISTIC COMBINATION OF COPPER(II) AND AMINE CATALYSIS
July 13, 2013
The enantioselective α-alkenylation of aldehydes has been accomplished using boronic acids via the synergistic combination of copper and chiral amine catalysis. The merger of two highly utilized and robust catalytic systems has allowed for the development of a mild and operationally trivial protocol for the direct formation of α-formyl olefins employing common building blocks for organic synthesis.
TOTAL SYNTHESIS OF IRCINIASTATIN A (PSYMBERIN)
May 01, 2010
The total synthesis of (+)-irciniastatin A (psymberin) is reported in 19 steps and 6% overall yield. Key reactions include a highly convergent enolsilane-oxocarbenium ion union to generate the C8-C25 fragment and a late-stage coupling of a hemiaminal and acid chloride to complete the synthesis.
TOTAL SYNTHESIS OF IRCINIASTATIN A (PSYMBERIN)
August 11, 2009
The total synthesis of (+)-irciniastatin A (psymberin) is reported in 19 steps and 6% overall yield. Key reactions include a highly convergent enolsilane-oxocarbenium ion union to generate the C8-C25 fragment and a late-stage coupling of a hemiaminal and acid chloride to complete the synthesis.
SYNTHESIS AND SAR OF VINCA ALKALOID ANALOGUES
February 15, 2009
Versatile intermediates 12′-iodovinblastine, 12′-iodovincristine and 11′-iodovinorelbine were utilized as substrates for transition metal based chemistry which led to the preparation of novel analogues of the vinca alkaloids. The synthesis of key iodo intermediates, their transformation into final products, and the SAR based upon HeLa and MCF-7 cell toxicity assays is presented. Selected analogues 27 and 36 show promising anticancer activity in the P388 murine leukemia model.