Master of Science (M.Sc.)
Robert J Hinkle
Christopher J Abelt
Heterocyclic aromatic compounds and their derivatives are ubiquitous in the pharmaceutical and photochemical industries. Naphthochromene derivatives in particular have garnered great interest for their photochemical properties and biological activity. Herein, the effects of electronics on a three-step cascade reaction between aryl substituted 2-(4-aryl-3-((triethylsilyl)oxy)but-1-yn-1-yl)phenols and structurally diverse aldehydes is explored. The cascade is initiated by alkynyl substrate addition to BF3-activated aldehydes. The aldehyde undergoes condensation with the substrate phenol moiety forming an oxocarbenium ion, this initiates the alkynyl-Prins cyclization forming a new six-membered heterocyclic ring with an internal alkenyl cation. The cation is subsequently trapped by a Friedel-Crafts (FC) reaction by the substituted ring and the cascade sequence is terminated by a dehydration step to afford 6H-naphtho[2,1-c]chromenes, adjoining an additional ring to the aromatic system. Substitution of the ring involved in Friedel-Crafts reaction with electron donating methyl groups and electron-withdrawing halogens afforded good yields of naphthochromenes, whereas the slightly electron-withdrawing methoxy- substituted substrate afforded extremely poor yields potentially due to deactivation of the ring to FC through coordination to Lewis acid or possible competitive dehydrative reactions. Further structural studies were carried out with 2-(3-(p-aryloxy)prop-1-yn-1-yl)phenols producing 6H,7H-chromeno[3,4-c]chromenes. Our findings followed expected trends with electron donating groups on the aryl ring participating in the FC reaction increasing overall yields and the deactivating nitro group affording the lowest yields with all aldehydes. Single crystal analysis of the dimethyl substituted tetracyclic product, 7dA, revealed a 55° out-of-plane twist between the two aromatic systems to decrease steric interactions.
© The Author
Burns, Caleb Lee, "Electronic Effects In A Cyclization Cascade To Diversified, Polycyclic, Helical Molecules" (2021). Dissertations, Theses, and Masters Projects. William & Mary. Paper 1638386822.
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