Two different strategies examine intramolecular cyclizations of chiral, metalated nitriles. Cyclizations onto allylic electrophiles through competitive SN2 or SN2' displacements have different trajectories reflecting the different conformations within the forming ring. Deuterium labeling with allylic electrophiles reveals an inherent preference for SN2 displacements reflecting the optimal orbital overlap for the two different geometries. / Bayer School of Natural and Environmental Sciences; / Chemistry and Biochemistry / MS; / Thesis;

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20395号 / 工博第4332号 / 新制||工||1671(附属図書館) / 京都大学大学院工学研究科物質エネルギー化学専攻 / (主査)教授 中村 正治, 教授 大江 浩一, 教授 村田 靖次郎 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

The ultimate goal of organic chemistry is understanding the processes involved in carbon-carbon bond formation. Metalated nitriles are perfectly suited for the regio- and stereospecific creation of sterically congested quaternary centers. These traits are dependent on the metal and the metal's preference for coordination to either the nitrile nitrogen lone pair of electrons or the electron pair of the "anionic" carbon bearing the nitrile. This thesis outlines the structural differences in solution between lithiated, cuprated, and magnesiated nitriles, providing the first such study of magnesiated nitriles. Nuclear magnetic resonance, which has become a powerful tool for a wide variety of structural elucidation, indicates both C- and N- binding modes for magnesium with a high dependence on other functionality present within the nitrile substrate. Carbon-carbon bond formation by the attack of a magnesiated nitrile on an alkene is highly unusual. An intramolecular carbo-magnesiation was serendipitously discovered that involves attack on a terminal alkene followed by addition to the nitrile to give a cyclobutanone. Microwave heating greatly enhances the carbometalation process although the carbometalation has only been achieved in two closely related substrates. Insight into the mechanism was obtained although the reaction scope has not yet been extended to other substrates. / Bayer School of Natural and Environmental Sciences; / Chemistry and Biochemistry / MS; / Thesis;

This thesis describes new methods of carbon-carbon bond formation using metalated nitriles generated via metal exchange reactions. Sulfinylnitriles undergo a sulfinyl-metal exchange to yield lithiated, magnesiated and zincated nitriles, which can trap a range of electrophiles. The sulfinyl-metal exchange is effective with vinylic, quaternary and tertiary substitution patterns and addresses the long-standing problem of alkylating secondary nitriles. This method was then further extended to other oxidation states of sulfur, namely sulfonyl-metal exchange and relatively unknown sulfide-metal exchange. The sulfide metal exchange overcomes the problem related to the propensity of highly substituted sulfinylnitriles to eliminate. Sulfide-metal exchange is synthetically attractive because of the numerous methods for generating arylsulfides and the high tolerance of arylsulfides to numerous reagents. <br>A copper-catalyzed arylation reaction of aryl iodides and metalated nitriles was developed using catalytic Cu (I) and an amine ligand. A proof of principle has been established, providing a sound basis for developing the reaction. A new strategy has been developed for alkylation of alkenenitrile using LDA as base in presence of catalytic CuCN. Subsequent trapping with an electrophile, affords alkylated alkenenitriles in which the olefin is no longer in conjugation with the nitrile. <br>The distinct structural differences between N- & C-metalated nitriles have been harnessed in a series of chemoselective alkylations. Lithiated nitriles are found to be particularly reactive toward alkyl halides whereas magnesiated nitriles react selectively with oxygenated electrophiles. Using this strategy allows chemoselective alkylation of metalated nitriles. / Bayer School of Natural and Environmental Sciences; / Chemistry and Biochemistry / PhD; / Dissertation;

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第17062号 / 工博第3611号 / 新制||工||1548(附属図書館) / 29782 / 京都大学大学院工学研究科物質エネルギー化学専攻 / (主査)教授 中村 正治, 教授 小澤 文幸, 教授 辻 康之 / 学位規則第4条第1項該当