Development of a radical Ti(III)-mediated cyclization cascade to synthesize trans-decalones from epoxynitriles

Milkovits, Amanda Anastasia

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https://hdl.handle.net/2142/115798 Copy

Description

Title

Development of a radical Ti(III)-mediated cyclization cascade to synthesize trans-decalones from epoxynitriles

Author(s)

Milkovits, Amanda Anastasia

Issue Date

2022-04-29

Director of Research (if dissertation) or Advisor (if thesis)

Sarlah, David

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• synthesis
• polyene cyclization
• titanocene
• titanium
• epoxide ring-opening
• trans-decalones
• stereoselective
• biomimetic

Abstract

Polyene cyclizations offer an elegant method to transform linear precursors into cyclic products. In particular, trans-decalins can be synthesized through two sequential ring formations. Starting from epoxynitrile olefins, Ti(III) can act as a radical initiator to open up the epoxide forming the tertiary free radical. This radical is then added into the alkene reversibly either kinetically via a 5-exo-trig ¬¬cyclization to give a cyclopentane ring with a secondary radical or thermodynamically via a 6-endo¬-trig cyclization to give the cyclohexane with the more stable tertiary radical. From the 6-membered intermediate, the radical adds into the nitrile to give the imine radical, which is hydrolyzed to the ketone. The goal was to take advantage of the stereochemistry of the epoxide precursors to provide a method for a stereospecific polyene cyclization to synthesize ¬trans-decalins with oxidation in either the equatorial or axial positions. Herein is described how this hypothesis was tested by using the cis and trans ¬isomers of trisubstituted epoxides to get to the axially and equatorially oxidized product respectively. Unfortunately, there was no stereospecificity; in all cases, the product was the equatorially oxidized trans¬-decalin. Disubstituted epoxides were also tested with the epoxide and protected or unprotected secondary alcohol syn to each other to give the equatorial product and with the epoxide and protected or unprotected secondary alcohol anti ¬to each other to give the axial product. Both substrates gave the thermodynamic trans¬-decalin with oxidation in the equatorial position. Overall, this radical cyclization method offers a facile synthesis of the thermodynamic trans-decalone with both the secondary alcohol and oxidized methyl group in the equatorial position. Selective protection of either the secondary or primary alcohol is possible depending on whether the disubstituted or trisubstituted epoxides are used.

Graduation Semester

2022-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 Amanda Milkovits

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