Microwave-Assisted Carbonyl–Carbonyl Coupling Route for the Preparation of a Useful Intermediate in the Synthesis of Carbapenems

Abstract

Microwave-assisted organic synthesis has been used for the cyclization of a monocyclic oxoamide to the corresponding bicyclic derivative via a Wittig-type coupling by means of phosphite reagents. The parameters influencing the reaction yields under microwave (dielectric heating) and classical conditions (convective heating) have been evaluated.

Keywords:

• Carbapenem
• imipenem
• MAOS (microwave-assisted organic synthesis)
• phosphite-mediated cyclization
• Wittig intramolecular reaction

ACKNOWLEDGMENTS

The authors thank the Ministry of Science and Technology (China) for the financial support (Grant No. 2006DFA43520). M. P. thanks Ministero Affari Esteri (MAE) for the financial support within the 12th Joint Commission on S & T Cooperation Between the People's Republic of China and the Italian Republic for the years 2006–2009. A. D. thanks Novachem Aromatici, Gallarate, Italy, for financial support.

Notes

Note. A ratio of 1/8/0.20 (in mmol) of oxoamide 2, TEP, and dihydroxybenzene was used in all the experiments reported.

^a The reaction temperatures were reached by applying a power of 280 W for CEM monomode and 300 W for MicroSYNTH.

^b Yields have been calculated for entries 1, 2, and 6 on pure isolated products. The yields for entries 3–5 and 6–12 were calculated by HPLC analysis by the support of a standard calibration curve. For entries 13–16, no traces of 1 were detected in HPLC analyses.

^c The product was fully identified by standard analytical data.

^d Monomode CEM-Discover was used as the microwave oven model.

^e Multimode MicroSYNTH (Milestone) was used as the microwave oven model.

^a µV is millivolts.