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A synthetic pathway for PET-labeled amides is described using rhodium-catalyzed coupling of organozinc iodide reagents and in situ prepared carbon-11 isocyanates. A scope prepared using carbon-12 isocyanates yielded products from 13-87% using readily prepared sp 3 and sp 2 organozinc iodides. By manipulation of fixation, dehydration, and coupling conditions, the incorporation of [ 11 C]CO2 into 11 C-amide products proceeded in moderate to strong yields, as determined by radioHPLC. Among the compounds prepared are the biologically-relevant tert-butyl protected [ 11 C]N-acetyl glutamic acid ([ 11 C]6d), the agrochemical [ 11 C]propanil ([ 11 C]6f), and a pharmaceutically-relevant [ 11 C]acetanilide ([ 11 C]4m). The synthetic utility of the labeling methodology was demonstrated through the isolation of [ 11 C]N-(4-fluorophenyl)-4-methoxybenzamide ([ 11 C]6g) with a molar activity of 267 GBq•mol -1 and a radioactivity yield of 12%, 21 minutes after beginning of synthesis.

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Iminophosphoranes are coupled with CO2 and carbon-, nitrogen-, oxygen-, and sulfur-based nucleophiles to synthesize acyclic (radio)pharmaceuticals in high yield.

Iminophosphoranes are reported as convenient precursors to amides, ureas, carbamates and other carbonyl-containing molecules through CO2-fixation. Key to this transformation with stable isotopes and carbon-11 is interception of the reactive isocyanate intermediate. Automated synthesis and isolation of PET radiopharmaceuticals is achieved.

a-Amino acids are among the essential chemical building blocks of life. These structures are embedded in many small molecule pharmaceuticals and are the primary components of peptide-based therapeutics and biologics. Isotopically labeled a-amino acids and their derivatives have widespread use in structural and mechanistic biochemistry, quantitative proteomics, absorption distribution metabolism and excretion (ADME) profiling, and as imaging agents in positron emission tomography (PET) techniques. The preparation of carbon-labeled a-amino acids remains difficult and time consuming, with established methods involving label incorporation at an early stage of synthesis. This explains the high cost and scarcity of C-labeled products and presents a major challenge in 11C applications (11C t1/2 = 20 min). Here we report that simple aldehydes catalyze the isotopic carboxylate exchange of native a-amino acids with *CO2 (* = 14, 13, 11). Proteinogenic a-amino acids and many non-natural variants containing diverse functional groups undergo labeling. The reaction likely proceeds via the trapping of *CO2 by imine-carboxylate intermediates to generate aminomalonates that are prone to monodecarboxylation. Tempering catalyst electrophilicity was key to preventing irreversible aldehyde consumption. The pre-generation of the imine carboxylate intermediate allows for the rapid and late-stage 11C-radiolabeling of a-amino acids in the presence of 11CO2.

Iminophosphoranes are reported as convenient precursors to amides, ureas, carbamates and other carbonyl-containing molecules through CO2-fixation. Key to this transformation with stable isotopes and carbon-11 is interception of the reactive isocyanate intermediate. Automated synthesis and isolation of PET radiopharmaceuticals is achieved.

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