Doctor of Philosophy, Harvard University (2016)
Carolyn Bertozzi, Postdoctoral Faculty Sponsor
Catalytic, Enantioselective 1,2-Difluorination of Cinnamamides
2019; 21 (13): 4919–23
The enantio- and diastereoselective synthesis of 1,2-difluorides via chiral aryl iodide-catalyzed difluorination of cinnamamides is reported. The method uses HF-pyridine as a fluoride source and mCPBA as a stoichiometric oxidant to turn over catalyst, and affords compounds containing vicinal, fluoride-bearing stereocenters. Selectivity for 1,2-difluorination versus a rearrangement pathway resulting in 1,1-difluorination is enforced through anchimeric assistance from a N- tert-butyl amide substituent.
View details for DOI 10.1021/acs.orglett.9b00938
View details for Web of Science ID 000474795200001
View details for PubMedID 30963766
Lysosome Targeting Chimeras (LYTACs) for the Degradation of Secreted and Membrane Proteins
View details for DOI 10.26434/chemrxiv.7927061.v1
Catalytic Diastereo- and Enantioselective Fluoroamination of Alkenes
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2018; 140 (14): 4797–4802
The stereoselective synthesis of syn-β-fluoroaziridine building blocks via chiral aryl iodide-catalyzed fluorination of allylic amines is reported. The method employs HF-pyridine as a nucleophilic fluoride source together with mCPBA as a stoichiometric oxidant, and affords access to arylethylamine derivatives featuring fluorine-containing stereocenters in high diastereo- and enantioselectivity. Catalyst-controlled diastereoselectivity in the fluorination of chiral allylic amines enabled the preparation of highly enantioenriched 1,3-difluoro-2-amines bearing three contiguous stereocenters. The enantioselective catalytic method was applied successfully to other classes of multifunctional alkene substrates to afford anti-β-fluoropyrrolidines, as well as a variety of 1,2-oxyfluorinated products.
View details for DOI 10.1021/jacs.8b02143
View details for Web of Science ID 000430155800011
View details for PubMedID 29583001
View details for PubMedCentralID PMC5902804
- Lewis acid enhancement by hydrogen-bond donors for asymmetric catalysis Science 2017; 358: 761-764
- Catalytic 1,3-Difunctionalization via Oxidative C–C Bond Activation Journal of the American Chemical Society 2017; 139 (27): 9152-9155
Catalytic, asymmetric difluorination of alkenes to generate difluoromethylated stereocenters
2016; 353 (6294): 51-54
View details for DOI 10.1126/science.aaf8078
- Catalytic, Diastereoselective 1,2-Difluorination of Alkenes Journal of the American Chemical Society 2016; 138 (15): 5000-5003
Chemoselective pd-catalyzed oxidation of polyols: synthetic scope and mechanistic studies.
Journal of the American Chemical Society
2013; 135 (20): 7593-7602
The regio- and chemoselective oxidation of unprotected vicinal polyols with [(neocuproine)Pd(OAc)]2(OTf)2 (1) (neocuproine = 2,9-dimethyl-1,10-phenanthroline) occurs readily under mild reaction conditions to generate α-hydroxy ketones. The oxidation of vicinal diols is both faster and more selective than the oxidation of primary and secondary alcohols; vicinal 1,2-diols are oxidized selectively to hydroxy ketones, whereas primary alcohols are oxidized in preference to secondary alcohols. Oxidative lactonization of 1,5-diols yields cyclic lactones. Catalyst loadings as low as 0.12 mol % in oxidation reactions on a 10 g scale can be used. The exquisite selectivity of this catalyst system is evident in the chemoselective and stereospecific oxidation of the polyol (S,S)-1,2,3,4-tetrahydroxybutane [(S,S)-threitol] to (S)-erythrulose. Mechanistic, kinetic, and theoretical studies revealed that the rate laws for the oxidation of primary and secondary alcohols differ from those of diols. Density functional theory calculations support the conclusion that β-hydride elimination to give hydroxy ketones is product-determining for the oxidation of vicinal diols, whereas for primary and secondary alcohols, pre-equilibria favoring primary alkoxides are product-determining. In situ desorption electrospray ionization mass spectrometry (DESI-MS) revealed several key intermediates in the proposed catalytic cycle.
View details for DOI 10.1021/ja4008694
View details for PubMedID 23659308