Nickel-catalyzed reductive ketone synthesis and stoichiometric reactivity of nickel(II) acyl halide complexes with organic halides

Thesis (Ph. D.)--University of Rochester. Dept. of Chemistry, 2016Chapter one focuses on the formation of ketones by nickel-catalyzed cross electrophile coupling of activated carboxylic acid derivatives and functionalized alkyl halides to give functionalized alkyl alkyl ketones. Use of this method allows for functionalized substrates to be used, including amines alcohols and even boronic esters. Stearicly hindered ketones can also be made by this method, a significant challenge for other procedures. The published work demonstrates 16 examples with 71% average yield and several more that are unpublished. Chapter two discusses a catalytic carbonylative cross-electrophile coupling of alkyl and aryl halides to form ketones. Only a small hand full of catalytic carbonylative cross-electrophile coupling reactions have been published. This method provides a convenient alternative to electrochemical and stoichiometric methods. The procedure allows for the rapid construction of aryl alkyl ketones from stable starting materials. The published work includes eight examples with 60% average yield. Chapter three, covers the previously unknown stoichiometric reactivity of bipyridine ligated acylnickel(II) halide complexes with alkyl and aryl halides. Acylnickel(II) complexes have been implicated as intermediates in several nickelcatalyzed reactions including acylation and carbonylation reactions discussed in chapters 1 and 2. This work reveals that these intermediates may be involved in the catalytic cycles for both carbonylation and acylation reactions. Selectivity for cross-ketone in the reactions of acylnickel complexes with organic halides ranges from 3:1 up to 20:1 with yields of the cross ketone up to 76% isolated

Synthesis of Functionalized Dialkyl Ketones from Carboxylic Acid Derivatives and Alkyl Halides

Unsymmetrical dialkyl ketones can be directly prepared by the nickel-catalyzed reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with alkyl iodides or benzylic chlorides. A wide variety of functional groups are tolerated by this process, including common nitrogen protecting groups and C–B bonds. Even hindered ketones flanked by tertiary and secondary centers can be formed. The mechanism is proposed to involve the reaction of a (L)Ni(alkyl)₂ intermediate with the carboxylic acid derivative

Stoichiometric Reactions of Acylnickel(II) Complexes with Electrophiles and the Catalytic Synthesis of Ketones

Acylnickel­(II) complexes feature prominently in cross-electrophile coupling (XEC) reactions that form ketones, yet their reactivity has not been systematically investigated. We present here our studies on the reactivity of acylnickel­(II) complexes with a series of carbon electrophiles. Bromobenzene, α-chloroethylbenzene, bromooctane, and iodooctane were reacted with (dtbbpy)­Ni^II(C­(O)­C₅H₁₁)­(Br) (<b>1b</b>) and (dtbbpy)­Ni^II(C­(O)­tolyl)­(Br) (<b>1c</b>) to form a variety of organic products. While reactions with bromobenzene formed complex mixtures of ketones, reactions with α-chloroethylbenzene were highly selective for the cross-ketone product. Reactions with iodooctane and bromooctane also produced the cross-ketone product, but in intermediate yield and selectivity. In most cases the presence or absence of a chemical reductant (zinc) had only a small effect on the selectivity of the reaction. The coupling of <b>1c</b> with iodooctane (60% yield) was translated into a catalytic reaction, the carbonylative coupling of bromoarenes with primary bromoalkanes (six examples, 60% average yield)