Strategic Applications of New Redox Transformations in Organic Synthesis

Krabbe, Scott

Strategic Applications of New Redox Transformations in Organic Synthesis Public Deposited

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March 19, 2019

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Krabbe, Scott
- Affiliation: College of Arts and Sciences, Department of Chemistry

Abstract

The dissertation contains three distinct parts. Part A: Aerobic hydroperoxidation of Meldrum's acid derivatives via a Cu(II)-catalyzed process is presented. The mild reaction conditions are tolerant to pendant unsaturation allowing the formation of endoperoxides via electrophilic activation. Cleavage of the O-O bond provides 1,n-diols with differentiation of the hydroxy groups. Part B: High-throughput screening enabled the development of a Cu-based catalyst system for the asymmetric hydrogenation of prochiral aryl and heteroaryl ketones that operates at H2 pressures as low as 5 bar. A ligand combination of (R,S)-N-Me-3,5-xylyl-BoPhoz and tris(3,5-xylyl)phosphine provided benzylic alcohols in good yields and enantioselectivities. The electronic and steric characteristics of the ancillary triarylphosphine were important in determining both reactivity and selectivity. A library of novel chiral trisphosphine ligands was also prepared and investigated. Part C: The asymmetric total syntheses of the alpha-benzylidene-gamma-butyrolactone natural products megacerotonic acid and shimobashiric acid A have been accomplished in nine and eleven steps, respectively, from simple, commercially available starting materials. The key step for each synthesis is the (arene)RuCl(monosulfonamide)-catalyzed dynamic kinetic resolution-asymmetric transfer hydrogenation (DKR-ATH) of racemic alpha,delta-diketo-beta-aryl esters to establish the absolute stereochemistry. Intramolecular diastereoselective Dieckmann cyclization forms the lactone core and ketone reduction/alcohol elimination installs the alpha-arylidene.

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