Investigation of new coupling reactions: Chromium mediated beta-lactone synthesis, palladium(II) catalyzed macrocyclization to form polyene macrocycles, and noncatalyzed functionalization of ethers with trimethylsilyl ketene

beta-Lactones are useful targets in organic chemistry owing to their rich reactivity, their occurrence in biologically active natural products, and most importantly their utility as "masked" aldol equivalents. The possibility of using Fischer chromium carbene complexes as an in situ source of ketene in a cycloaddition with aldehydes was investigated. It was found that when this reaction was catalyzed by DMAP the diastereoselectivity of the process was extremely high. Furthermore, unactivated aldehydes are effective substrates for this transformation suggesting the mechanism differs from that of Wynberg lactonization. A new mechanism has been postulated wherein aninitially formed chromium bound ammomium enolate acts to activate the aldehyde and cyclization occurs via a chair-like transition state.; In another investigation, the palladium(II) catalyzed intramolecular cyclization of bisvinylboronates to generate E,E diene macrocycles has been pursued and shown to be effective. This means of preparing polyene macrocycles is advantageous over existing palladium(0) catalyzed routes (e.g., the Stille or Suzuki reactions) because it utilizes a symmetrically substituted precursor that may be prepared in fewer synthetic manipulations. Macrocyclization occurs through a series of two transmetallation between the palladium(II) catalyst and the two binylboronates under dilute conditions to generate a macropalladicycle. Reductive elimination results in formation of the desired macrocycle and palladium(0) is reoxidized to palladium(II) by a stoichiometric oxidant.; Finally, we have discovered that TMS-ketene reacts with ethers to functionalize the latter at the alpha-carbon leading to a-silyl ketones in good yields. The reaction is proposed to occur by means of a proton transfer of an initially formed ketene-ether complex followed by [1,2] Stevens type shift to generate the a-silyl ketones.