The ubiquitous presence of carbon in small molecule exogenous compounds makes it attractive for isotopic labeling. Carbon-11 radiochemistry, despite its relatively short half-life, offers numerous opportunities for tagging molecules with a positron emitter. Nucleophilic [11C]methylations with [11C]CH3I or [11C]CH3OTf have long been used to generate some of the most prominent radiotracers. To expand this field, we seek to build upon a strong foundation of [11C]CO2 radiochemistry and advance mild reduction chemistries. These will permit robust amide reductions to access heteroatom-alkyl chains longer than methyl and for direct methylation of amines through fixation-reduction mechanisms. Moreover, we are seeking to improve the production and expand the reaction scope of underutilized synthons (CH3NO2, CH2O, CHF3, or CF2O).
