The scope and limitations of microwave heating as a tool for insertion of Group 10 metals into meso-tetraphenyl-porphyrin, -porpholactone, and -2,3-dihydroxychlorin derivatives are discussed. In some cases it is possible to reduce reaction times dramatically while obtaining good yields of the metallated products while in others new issues arise relating to the metal salt used as well as acceleration not only of the metallation reaction but also of byproduct formation.

A new batch microwave reactor has been evaluated in the context of palladium-mediated transformations, condensation reactions, nucleophilic aromatic substitution reactions, and alkylations. Importantly, a linear scaling approach was taken, no changes being made to the protocol when moving from the small, developmental scale to larger scales. In some cases reactions were scaled over 18,000-fold when moving from small (0.1-1 mmol) to large (1-18 mol) runs.

A range of synthetic transformations have been scaled up successfully using a sealed-vessel multimode microwave unit. These include metal-catalyzed couplings, synthesis of heterocycles, reactions under an atmosphere of reactive gas and two-step one-pot procedures. Also, observations have been made along the way that are of use to chemists addressing scale-up of microwave-promoted reactions.

Acylsilanes serve as acyl anion equivalents in a palladium-catalyzed cross-coupling reaction with aryl bromides to give unsymmetrical diaryl ketones. Water plays a unique and crucial activating role in these reactions. High-throughput experimentation techniques provided successful reaction conditions initially involving phosphites as ligands. Ultimately, 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane was identified as giving a longer-lived catalyst with higher turnover numbers. Its use, in conjunction with a palladacycle precatalyst, led to optimal reaction rates and yields. Scope and limitations of this novel method are presented along with initial mechanistic insight.