Synthesis of dihydroindenofuran scaffold via a Pd-catalyzed 5-endo-trig cyclization/enolate O-alkylation cascade

An efficient synthesis of dihydroindenofurans was carried out starting from the Baylis-Hillman adducts via a Pd-catalyzed 5-endo-trig-carbopalladation and enolate O-alkylation cascade as a key step. This is the first example of enolate O-alkylation with a C(sp³)-bound palladium intermediate.     

A new synthesis of pyrrolidines via imino-aldol reaction of (2-trimethylsilylmethyl)cyclopropyl ketones with imines

A new synthesis of 2,3,5-trisubstituted pyrrolidines from the imino-aldols formed from Lewis acid-mediated reactions of (2-trimethylsilylmethyl)cyclopropyl ketones with benzylimines is described. The ring closure of the imino-aldols formed from the benzylimines of 2-chloro-, 2-fluoro-, and 2-trifluoromethylbenzaldehydes proceeds with predominantly 2,5-anti selectivity to generate the corresponding pyrrolidines in moderate yields.     

Palladium-catalyzed mono-γ-arylation of 7-methoxy-4-methylcoumarin

Herein, we report the selective mono-γ-arylation of 7-methoxy-4-methylcoumarin under palladium-catalyzed conditions. The Buchwald G3 pre-catalyst in conjunction with either the Xantphos or N-Xantphos ligand proves to be highly reactive, engaging aryl iodides, bromides, chlorides, and triflates to effect the desired transformation. A wide range of functionality is tolerated, including the ability to activate heteroaryl halides in the transformation. The initial scope of aryl halides and limitations of this methodology are presented.     

Palladium-catalysed arylation of acetoacetate esters to yield 2-arylacetic acid esters

The coupling reaction between ethyl acetoacetate and a number of aryl halides in the presence of palladium acetate, a bulky and electron rich phosphine and K₃PO₄ is described. The arylated acetoacetate ester is de-acylated under the reaction conditions resulting in the generation of 2-arylacetic acid esters, constituting a mild alternative to direct arylation of carboxylate esters.     

The preparation and reaction of enolates within micro reactors

Over the past 5 years, interest in the miniaturisation of chemical synthesis has grown rapidly, however in order to facilitate transfer of the technology from its current position as a research tool to industrial applications, a core understanding of the challenges associated with transferring reactions from the macro to the micro domain is required. This paper therefore aims to broach this problem by investigating the application of micro reactors to a range of commonly employed synthetic reactions including acylation, aldol, alkylation, 1,4-conjugate addition (Michael addition) and the Knoevenagel condensation. Comparison of the results obtained with traditional batch techniques enable us to highlight some of the advantages associated with micro reaction technology.