This Account summarizes predominately our own experiences in developing microwave-heated palladium-catalyzed Mo(CO)₆-mediated gas-free carbonylative reactions, although contributions from other groups, including non-palladium-catalyzed examples, have also been covered. Presented reactions include amino-, amido-, and alkoxycarbonylations as well as carbonylative cyclizations and carbonylative cross-couplings, using Mo(CO)₆ as a solid source of CO. The methodology was developed mainly for rapid small-scale applications, avoiding the problematic use of gaseous CO in a standard laboratory. In most cases, the reported Mo(CO)₆-mediated carbonylations were conducted in sealed vessels and with reaction times of less than 1 hour. The Account also highlights relevant applications in medicinal and high-speed chemistry. 1 Introduction 2 Mo(CO)₆-Promoted Carbonylations - The Beginning 3 Aminocarbonylations 4 Amidocarbonylations 5 Alkoxy- and Hydroxycarbonylations 6 Carbonylative Ring Closing of Aryl Halides 7 Carbonylative Cross-Couplings 8 Palladium-Free Mo(CO)₆-Promoted Carbonylations 9 Summary and Outlook

A reductive lignocellulose fractionation in a flow-through system in which pulping and transfer hydrogenolysis steps were separated in time and space has been developed.

The overexpression of gastrin-releasing peptide receptor (GRPR) in cancer can be used for peptide-receptor mediated radionuclide imaging and therapy. We have previously shown that an antagonist analog of bombesin RM26 conjugated to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) via a diethyleneglycol (PEG₂) spacer (NOTA-PEG₂-RM26) and labeled with ⁶⁸Ga can be used for imaging of GRPR-expressing tumors. In this study, we evaluated if a variation of mini-PEG spacer length can be used for optimization of targeting properties of the NOTA-conjugated RM26. A series of analogs with different PEG-length (n = 2, 3, 4, 6) was synthesized, radiolabeled and evaluated in vitro and in vivo. The IC₅₀ values of ^natGa-NOTA-PEG_n-RM26 (n = 2, 3, 4, 6) were 3.1 ± 0.2, 3.9 ± 0.3, 5.4 ± 0.4 and 5.8 ± 0.3 nM, respectively. In normal mice all conjugates demonstrated similar biodistribution pattern, however ⁶⁸Ga-NOTA-PEG₃-RM26 showed lower liver uptake. Biodistribution of ⁶⁸Ga-NOTA-PEG₃-RM26 was evaluated in nude mice bearing PC-3 (prostate cancer) and BT-474 (breast cancer) xenografts. High uptake in tumors (4.6 ± 0.6%ID/g and 2.8 ± 0.4%ID/g for PC-3 and BT-474 xenografts, respectively) and high tumor-to-background ratios (tumor/blood of 44 ± 12 and 42 ± 5 for PC-3 and BT-474 xenografts, respectively) were found already at 2 h p.i. of ⁶⁸Ga-NOTA-PEG₃-RM26. Results of this study suggest that variation in the length of the PEG spacer can be used for optimization of targeting properties of peptide-chelator conjugates. However, the influence of the mini-PEG length on biodistribution is minor when di-, tri-, tetra- and hexaethylene glycol are compared.

The concept of a nonresonant microwave applicator for continuous-flow organic chemistry is introduced and evaluated. The frequency of the incident microwave radiation can be adjusted between 2.4 and 2.5 GHz to optimize the energy absorbance. The temperature of the reaction is monitored by five IR sensors, and their signals can be used to automatically adjust the power output from the microwave generator. The heating of several different solvents up to 20 °C above the standard boiling point has been explored. Several different organic reactions have been successfully carried out using a 200 mm × ⌽ 3 mm tubular borosilicate reactor and a flow between 47 and 2120 μL/min. The microwave heating pattern was visualized with an IR camera. The transformations include palladium-catalyzed coupling reactions (oxidative Heck and Suzuki reactions), heterocyclic chemistry (oxathiazolone and Fischer indole synthesis), rearrangement (Claisen), and a Diels–Alder cycloaddition reaction. A scale-out to 57 mmol/h was performed with the Fischer indole reaction.

Cinnamaldehyde derivatives were synthesized in good to excellent yields in one step by a mild and selective, base-free palladium(II)-catalyzed oxidative Heck reaction starting from acrolein and various arylboronic acids. Prepared α,β-unsaturated aldehydes were used for synthesis of novel α-aryl substituted fosmidomycin analogues, which were evaluated for their inhibition of Mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate reductoisomerase. IC₅₀ values between 0.8 and 27.3 μM were measured. The best compound showed activity comparable to that of the most potent previously reported α-aryl substituted fosmidomycin-class inhibitor.