Development of methodologies for reactions involving gases as reagents: microwave heating and conventionally-heated continuous-flow processing as examples

Abstract

Microwave (MW) heating and conventionallyheated continuous-flow processing have emerged as viable alternatives to the traditional methods of preparing organic compounds. These tools enable the chemist to circumvent some of the issues associated with conventional processing, while improving the efficiency of chemical transformations. Recently, several strategies have been developed to perform reactions using gaseous reagents, employing MW heating or conventionally-heated microand meso-flow technologies. This perspective describes some of these strategies by means of a discussion of work performed in our laboratory, focused around alkoxycarbonylation and hydrogenation reactions.

The Hitchhiker’s Guide to Flow Chemistry

“…Carbon monoxide (CO) is a colorless, odorless, and tasteless gas which is extremely toxic, even at low concentrations. Nevertheless, this hazardous gas is an important C 1 building block offering the possibility to install a carbonyl group into organic molecules via the transition metal catalyzed formation of two new σ-bonds. − Various research groups have evaluated the feasibility of continuous flow chemistry as a safe and efficient tool for catalytic carbonylation reactions using gaseous CO ,− and CO surrogates. ,, …”

The Use of Gases in Flow Synthesis

“…The use of a reverse tube-in-tube configuration was exemplified by Leadbeater and co-workers for the carbonylation of several aryl iodides to give the alkoxy carbonylative products in excellent conversions (91–99%, 8 examples) (Scheme ). The same group also published a carbonylative system in which a plug flow system was used, and, although it showed superior yields to the batch systems, it was still not as efficient as the reverse tube-in-tube system …”

Microwave irradiation as a sustainable tool for catalytic carbonylation reactions

“…This represents an important evidence that microwave heating was crucial to promote the cyclization process. Moreover, bicylic (13)(14)(15)(16)(17)(18), tricyclic (19), tetracyclic (20)(21) and spirocyclic (22) oxazolopiperidines ( Fig. 4) could also be prepared in good yields and acceptable stereoselection [33].…”

“…Another microwave pioneers, Chris Strauss and Mats Larhed, have also decisively contributed for the development of microwave reactions [13,14], which have evolved to their application in many catalyzed reactions involving gas reactants [15] such as methane oxidation and oligomerization [16][17][18], nitrogen fixation reactions [19] and also ethylene derivatization [17]. More recently, improvements in commercial microwave ovens for organic synthesis allowed the controlled introduction of gases inside the reaction tube with consequent preparation of value-added products via well-known catalytic reactions, under moderate conditions and in some cases with higher reaction selectivities [20][21][22]. Among the application of catalytic reaction for development of sustainable organic processes, the catalytic carbonylation reaction [ 23 ] and hydroformylation [ 24 -27 ] must be highlighted since it represent the major technology for the production of value-added bulk and fine chemicals from olefins [ 28 ].…”