Author Mulrooney, Carol A
Title Substrate scope of the asymmetric biaryl coupling reaction. Asymmetric synthesis of a perylenequinone. Progress toward the synthesis of cercosporin
book jacket
Descript 278 p
Note Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3806
Adviser: Marisa C. Kozlowski
Thesis (Ph.D.)--University of Pennsylvania, 2006
The Kozlowski group has developed an asymmetric copper-catalyzed oxidative biaryl coupling reaction using a novel 1,5-diaza-cis-decalin ligand. This reaction gives good yields and enantioselectivities for a number of 3-substituted 2-naphthols to yield new BINOL derivatives. A substrate scope has been explored yielding insight into the utility and reaction mechanism. Compounds that have chelating groups in the 3-position are optimal for biaryl coupling. A series of 3-sulfone-2-naphthols is described for this reaction. The geometry and the electron-withdrawing character of the substituent are important for optimal coupling. The oxidation potential of the naphthol is important for oxidation, electron-donating substituents placed in the system have an effect on the yield and enantioselectivity of the reaction.*
To explore the utility of the reaction further toward the synthesis of natural products and their derivatives, a series of highly substituted 2-naphthols was synthesized in order to explore the synthesis of perylenequinone natural products. Building on previously established successful biaryl couplings of highly substituted 2-naphthols, a model system was developed toward the synthesis of a perylenequinone derivative with the axial chirality as the only chiral element. Initial progress via an ortho-quinone led to racemized product. A nucleophilic aromatic substitution reaction was utilized to provide the oxygenation needed to transform the highly substituted biaryl 47 to a chiral perylenequinone.*
Steps toward the synthesis of the natural product cercosporin were then developed. A mild decarboxylation reaction was employed to remove the methyl esters that were necessary for asymmetric biaryl coupling but not present in the natural product. An allyl group was introduced in the C7 position that would be later used to introduce the chiral alcohols in the side chains. The 7-membered ring present in cercosporin was introduced by C5/C5' hydroxylation, then a selective deprotection strategy followed by methylenation yielded intermediate 124. Initial studies toward the introduction of the C7/C7' chiral secondary alcohols proved disappointing. A survey of chiral reductions was initiated on a model system with moderate enantioselectivities achieved. Future plans are proposed to introduce the chiral secondary alcohol via reduction of a ketone with various chiral ligands.*
*Please refer to dissertation for diagrams
School code: 0175
DDC
Host Item Dissertation Abstracts International 67-07B
Subject Chemistry, Organic
0490
Alt Author University of Pennsylvania