Enantioselective Deaminative Alkylation of Amino Acid Derivatives with Unactivated Olefins

Abstract

Herein, we report the first Ni-catalyzed enantioselective deaminative alkylation of amino acid and peptide derivatives with unactivated olefins. Key for success was the discovery of a new sterically encumbered bis(oxazoline) ligand backbone, thus offering a de novo technology for accessing enantioenriched sp 3 −sp 3 linkages via sp 3 C−N functionalization. Our protocol is distinguished by its broad scope and generality across a wide number of counterparts, even in the context of late-stage functionalization. In addition, an enantioselective deaminative remote hydroalkylation reaction of unactivated internal olefins is within reach, thus providing a useful entry point for forging enantioenriched sp 3 −sp 3 centers at remote sp 3 C−H sites.

Stereoretentive cross-coupling of chiral amino acid chlorides and hydrocarbons through mechanistically controlled Ni/Ir photoredox catalysis

“…The use of 2,6-di- tert -butylpyridine led to a huge loss of reaction efficiency, demonstrating that a sterically more hindered pyridine derivative lowers the reactivity (entry 7) 50 . 2,4,6-Triphenylpyridine, which may form an acyl analog of the Katritzky salt 51 , 52 , generated the targeted product in a moderate yield (entry 8). When 2,6-lutidine was replaced with common inorganic bases such as cesium carbonate, sodium bicarbonate, or potassium phosphate, the reaction efficiency decreased significantly (entries 9–11).…”

Repurposing amine and carboxylic acid building blocks with an automatable esterification reaction

“…Our scope studies were expanded to include Katritzky salts derived from primary aliphatic amines (29, 31, 36-40, 42, 43), as well as electron-poor or heterocyclic benzylic amines (30,41,44), although these substrates required heating to 110 °C. The method is quite general, tolerating basic amines (39)(40)42), amides (32), esters (35)(36)(37)(38), Michael acceptors (41), acetals (36,38), protecting groups including Boc and tosyl (29,(36)(37)(38), and oxime ethers (43) as well as polyfunctionalities seen in drug molecules such as levofloxacin (33), Boclysine methyl ester (37) enoxolone (41), and fluvoxamine (43). 39 and 40 are matched molecular pairs of moclobemide and metoclopramide, respectively, wherein the nitrogen atom has been replaced by an oxygen.…”

Catalytic Photochemical Enantioselective α-Alkylation with Pyridinium Salts

“…12,13,14,15,16 More recently, pyridinium salts have been utilized in deaminative transformations through activation by photoredox catalysis 17 or the formation of CT complexes with electron rich molecules. 18 Despite the widespread application of pyridinium salts as radical precursors, the use of these substrates in catalytic enantioselective transformations is rare, 19 and enantioselective reactions with prochiral enolate equivalents is unprecedented. We initiated our studies by coupling hydrocinnamaldehyde 9 with Katritzky salt 10a derived from the ethyl ester of glycine (Table 1).…”