Nickel-catalyzed hydroarylation, hydroboration and arylative substitution reactions

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2022-05
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Tran, Hai Ngoc
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Stanley, Levi
Kraus, George
VanVeller, Brett
Winter, Arthur
Kovnir, Kirill
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Chemistry
Abstract
This dissertation presents developments of catalytic methods for alkene functionalization reactions using nickel catalysts. These developments include 1) asymmetric hydroarylation of vinylarenes; 2) enantioselective hydroboration of vinylarenes; and 3) arylative substitution of homoallylic alcohols. Chapter II describes the enantioselective hydroarylation of vinylarenes catalyzed by a chiral, non-racemic nickel catalyst as a facile method to generate chiral 1,1-diarylethanes. These reactions proceed via formation of a chiral, non-racemic nickel benzyl intermediate. Transmetalation with arylboron nucleophiles and subsequent reductive elimination enable the formation of a variety of chiral 1,1-diarylethanes. The 1,1-diarylethane products from reactions of arylboronic acids containing electron-donating substituents are formed with typically greater than 90% ee, while the 1,1-diarylethanes generated from reactions of arylboronic acids containing electron-withdrawing groups are generated with typically less than 80% ee. These results are consistent with the rate of transmetalation with an arylboron nucleophile playing a key role in the enantioselectivity of these hydroarylation reactions. This mechanistic insight has led to the development of reactions of neo-pentylglycolate esters of arylboronic acids with vinylarenes that occur with higher enantioselectivities based on increased rates of transmetalation. Chapter III describes the enantioselective hydroboration of vinylarenes catalyzed by a chiral, nonracemic nickel catalyst as a facile method for generating chiral benzylic boronate esters. Various vinylarenes react with bis(pinacolato)diboron (B2pin2) in the presence of MeOH as a hydride source to form chiral boronate esters in up to 92% yield with up to 94% ee. The use of anhydrous Me4NF to activate B2pin2 is crucial for ensuring fast transmetalation to achieve high enantioselectivities. Chapter IV describes the nickel-catalyzed arylative substitution of homoallylic alcohols. Direct coupling of unactivated alcohols remains a challenge in current synthetic chemistry. Current approaches to cross-coupling of alcohol-derived electrophiles often involve activated alcohols such as tosylates or carbonates. We report the direct arylative substitution of homoallylic alcohols catalyzed by a nickel-bisphosphine complex as a facile method to generate allylic arenes. These reactions proceed via formation of an α-aryl allyic alcohol intermediate. Subsequent allylic substitution with arylboroxine nucleophiles enables the formation of a variety of allylic arenes. The presence of p-methoxyphenylboronic acid is crucial to activate the α-aryl allylic alcohol to achieve high product yields.
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