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Authors: Provencher, Philip Andrew
Advisors: Sorensen, Erik J
Contributors: Chemistry Department
Keywords: Benzocyclobutene
C-H Functionalization
Subjects: Chemistry
Issue Date: 2022
Publisher: Princeton, NJ : Princeton University
Abstract: C‒H functionalization promises the rapid and efficient synthesis of desired molecules from simple starting materials. One can envision a future where short sequences of catalytic C‒H functionalization can rapidly synthesize complex molecules in high yields, however current synthetic strategies tend to use traditional functional group interconversion to build up molecular complexity. In this thesis, we propose the arene unit as a two-carbon synthon to couple C‒H functionalizations in sequence to rapidly and selectively make benzo-fused carbocycles. To do this, an intramolecular arylation methodology was developed and optimized. This process was aided by computational study, which indicated that the transition state of highest energy comprised the first intramolecular step in ring formation, and that the Ag(I) additive was critical in geometric relaxation at the Pd center. This methodology enabled the execution of relay C‒H functionalization to form the indane unit by sequential intermolecular methyl/intramolecular methylene C‒H arylation in a formal {3+2] ring construction. Interestingly, this study presented the question: why does Pd(II) selectively activate methyl C‒H bonds in the presence of equidistant linear methylene C‒H bonds? Subsequently, methodology was developed that formed the benzocyclobutene unit through selective activation of a linear methylene C‒H bond in the presence of equidistant methyl C‒H bonds. Computational study showed that this selectivity was due to a subtle combination of ligand-substrate interaction and the inherent preference of geometry by Pd(IV) formed by oxidative addition. Selective intramolecular arylation of methylene C‒H bonds not only accessed the useful benzocylobutene moiety in a fundamentally interesting and new way, but it also preserved an α-methyl ketone unit, which is a privileged reactive functionality in Pd catalyzed C‒H functionalization and therefore permitted sequential C‒H arylation.
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Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Chemistry

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