Diastereoselective Synthesis of Planar Chiral N-Substituted Ferrocenes Derived from Epimeric Imidazolones and their Application to Asymmetric Hydrogenation of Quinolines

This thesis describes the synthesis and use of an N-substituted ferrocene bearing a proline-derived chiral directing group and diastereoselective lithiation-electrophile quench of the pro-Sp hydrogen of the ferrocene to give planar chiral products in >95:5 dr. The auxiliary group is found to be stable to lithium bases of types RLi and R2NLi giving the same diastereoselectivity. The anti- epimer of the previously mentioned syn auxiliary induces lithiation of pro Rp rather than pro Sp hydrogen in >95:5 dr. Upon electrophile quench and elimination, the enantiomer of the syn-derived planar chiral imidazolone is obtained. Hence, this method provides a practical way to prepare planar chiral enantiomers in this series without the use of a more expensive D-proline derived starting material. The syn and anti epimers have β, γ-stereogenic centers and the origin of stereoselectivity in lithiation appears to be driven by the conformational bias exerted by the β-silyloxy moiety in each chiral auxiliary. In the thesis, this conclusion is supported using insensitivity of lithiation selectivity to the bulkiness of the base, comparison of enantiomers, deuteration experiments, nOe difference studies and computational modeling of the ground states and lithiation transition states for both substrates. The products are then converted to ligand precursors to make iridium and rhodium complexes. Among them, one of the cationic iridium complex is found to be effective in the asymmetric hydrogenation of 2-substituted quinolines with enantioselectivities up to 80% at pressures as low as 5 atm.

A Bicyclic L-Proline Derived Chiral Auxiliary for Asymmetric Synthesis

This thesis describes the use of an L−proline-derived chiral auxiliary for diastereoselective lithiation and ligand synthesis. Such compounds have been utilized in the Metallinos research group previously for the synthesis of N−substituted planar chiral ferrocenes. The first project describes the use of this chiral auxiliary as a directing group for N−benzyl substitution, providing products in up to 10:1 diastereomeric ratio (dr). These derivatives may serve as chiral ylidene precursors to serve as ligands in transition metal catalysis. In addition, an N−substituted planar chiral ferrocene ylidene ligand derived from the same chiral auxiliary was used to prepare rhodium complexes that were explored as potential catalysts for asymmetric hydroformylation.

Science Complex Opening

Pictured here from left to right are James Gibson, President Emeritus, R. A. Macleod, Board of Trustees, and Dr. Cecil Shaver, former Chancellor, during the 1984 Science Complex opening - an addition to the Mackenzie Chown Complex now simply known as H Block.

Science Complex Opening

Pictured here from left to right are Henry Tomarin, Board of Trustees, St. Catharines Mayor Roy Adams, R. Campbell, Niagara Region chairman, Peter Misener, and R. Misener, Chancellor, during the 1984 Science Complex opening - an addition to the Mackenzie Chown Complex now simply known as H Block.

Science Complex Opening

Dr. Earp unveils a sign at the joint Science Complex opening ceremony and the Academic Staging Building renaming ceremony. The Academic Staging Building was henceforth called the Mackenzie Chown Complex.

Science Complex Opening

Dr. Alan Earp speaks at the opening ceremony for the Science Complex addition in 1984.

Science Complex Opening

Doris Chown speaking at the Science Complex Opening and the unveiling of a sign in conjunction with the renaming of the Academic Staging Building to the Mackenzie Chown Complex.

Science Complex Opening

Robert S. K. Welch celebrates the opening of the new Science Complex wing, an addition to the Mackenzie Chown Complex, as Dr. Alan Earp (pictured behind Welch) and others look on. The new name for the Academic Staging Building was also unveiled. It was renamed after former mayor Mackenzie Chown.

Science Complex Opening

Rather then cutting a piece of red tape with scissors, the Science students at Brock prepared a laser devise to cut through a specially made piece of metallic ribbon for the opening ceremony of the Science Complex addition. Pictured here is Robert Welch with the laser device as he attempts to 'cut' the tape. Unfortunately the device failed and Dr. Earp resorted to cutting the tape with a Swiss Army knife he had on hand.

Greenhouse and Science Complex

The Aumni Greenhouse and the Science Complex in the background.

Complex Model

Mackenzie Chown Complex model.

Complex Model

View of the Mackenzie Chown Complex model from above.

Science Complex Model

A model showing the Mackenzie Chown complex and the H Block addition.

Complex takes shape

View of the progress of the Mackenzie Chown Complex several months into construction.

Science Complex Construction

Initial groundwork taking place during the construction of the addition.