| Molecules containing two quaternary bridgehead carbon atoms connected by four non-zero-length bridges are commonly referred to as [n.o.p.q]paddlanes, where n, o, p and q represent the lengths in descending order of the four bridges. When the carbon atoms adjacent to these bridgeheads incorporate ketone groups, the molecules are known as [n.o.p.q]paddlanediones. This thesis presents syntheses and x-ray crystal structures of three homologous paddlanediones---[14.2.2.2]paddlanedione, [12.2.2.2]paddlanedione, and [10.2.2.2]paddlanedione---and new synthetic methodologies of general applicability that were developed in the course of their preparation.;Bridgehead functionalized bicyclo[2.2.2]octanes are important systems for physical organic studies as well as useful building blocks for synthesis and materials science. Dimethyl bicyclo[2.2.2]octane-1,4-dicarboxylate and its half-ester, monomethyl bicyclo[2.2.2]octane-1,4-dicarboxylate, serve as precursors to most bridgehead functionalized bicyclo[2.2.2]octanes. Neither is sold commercially and their availability, traditionally, has been limited to low-yielding or otherwise inconvenient preparations. This thesis describes short (two- and three-step, respectively), high-yielding syntheses of both materials starting from the commercially available and inexpensive reagents, dimethyl cyclohexane-1,4-dicarboxylate and 1-bromo-2-chloroethane. These syntheses are amenable to scale-up and circumvent all difficulties associated with earlier routes.;The classical Claisen formylation of ketones, one of the oldest and most widely invoked reactions in organic synthesis, remained the only ketone condensation reaction not yet successfully performed under conditions of kinetic control. This thesis describes the first general method for direct formylation of kinetically-generated ketone enolates. When 2,2,2-trifluoroethyl formate was added to ether solutions of preformed, kinetically-generated ketone enolates at -78°C, the corresponding alpha-formyl ketones were obtained in good yield. This method enables a complete reversal in the regioselectivity of the classical Claisen reaction and provides a superior method for the alpha'-formylation of alpha,beta-unsaturated ketones. |
