Cross‐Coupling of Alkyl Redox‐Active Esters with Benzophenone Imines: Tandem Photoredox and Copper Catalysis

Abstract

Alkyl amines are an important class of organic compounds in medicinal and materials chemistry. Until now very have been very few methods for the synthesis of alkyl amines by metal-catalyzed cross-coupling of alkyl electrophiles with nitrogen nucleophiles. Described here is an approach to employ tandem photoredox and copper catalysis to enable the cross-coupling of alkyl N-hydroxyphthalimide esters, readily derived from alkyl carboxylic acids, with benzophenone-derived imines. Hydrolysis of the coupling products furnish alkylated primary amines. Primary, secondary, and tertiary alkyl groups can be transferred, and the coupling tolerates a diverse set of functional groups. The method allows rapid functionalization of natural products and drugs, and can be used to expedite syntheses of pharmaceuticals from readily available chemical feedstocks.

Synthesis of Indoles through Domino Reactions of 2‐Fluorotoluenes and Nitriles

“…It is noteworthy that 3kaexhibits significant bioactivity against the Gram-positive pathogen Bacillus cereus. [20] In general, polyfluorotoluenes were also viable substrates, affording the corresponding indoles in 90, 78, and 87 % yield (3ra-3ta), respectively (entries [18][19][20]. Some substrates were found to be sensitive to the conditions and required additional optimization (see the Supporting Information for details).…”

Photoredox-catalyzed stereoselective alkylation of enamides with N-hydroxyphthalimide esters via decarboxylative cross-coupling reactions

“…Recent advances in this arena have witnessed a rapid development in a broad range of decarboxylative cross-coupling reactions to forge C(sp 3 )–C or C(sp 3 )–X (X = Si, B, Se, etc. ) bonds via transition-metal14,15 and photoredox catalysis,16,17 as elegantly established by the groups of Baran,14a–g,o,15b Weix,14h,i Fu,16c–g,17a,b Oestreich,15 Phipps,16 a Xiao,16 l and many others 18. Very recently, Fu and co-workers demonstrated a brand new catalytic combination of sodium iodide and triphenylphosphine for the cross-coupling of redox-active esters with silyl enol ethers or heteroarenes without resorting to the use of dye or transition-metal based photocatalysts 19.…”

Cu-Catalyzed Decarboxylative Borylation

“…This work constitutes another example of the use of Cu-catalysis for inducing decarboxylation of redox-active esters. 12 , 20 In the present case, inexpensive and rapid access to boronic esters combined with a clear analysis of concentration dependences may facilitate large-scale adoption. The simple experimental protocol described herein might inspire other radical-based cross couplings and functional group interconversions using Cu.…”