Enantioconvergent Fukuyama Cross‐Coupling of Racemic Benzylic Organozinc Reagents

Abstract

The first enantioconvergent palladium-catalyzed Fukuyama cross-coupling of racemic benzylic organozinc reagents with thioesters has been developed. The reaction furnishes enantioenriched acyclic α-disubstituted ketone products in good yields and high enantioselectivities. A broad substrate scope is achieved under mild reaction conditions to prevent racemization of the potentially labile tertiary stereocenters.

Metal‐Catalyzed Synthesis and Use of Thioesters: Recent Developments

“…The reaction has since then been expanded to accommodate secondary organozinc coupling partners . Notably, a highly stereoconvergent catalytic system, which forms tertiary stereocenters from racemic benzyl zinc reagents and thioesters 24 , has been disclosed by Maulide's group (Scheme ) . They used an enantiopure chiral phosphoramidite ligand ( L6 ) as the stereoinducing element to affect a dynamic kinetic resolution (DKR) of the zinc reagent.…”

“… Maulide's synthesis of tertiary stereocenters by an enantioconvergent Fukuyama reaction . MTBE: methyl‐ tert ‐butyl ether.…”

Enantioselective CuH-Catalyzed Hydroacylation Employing Unsaturated Carboxylic Acids as Aldehyde Surrogates

“…1 While a number of catalytic methods exist for preparing enantioenriched quaternary α-aryl ketones 2 , catalytic assembly of acyclic tertiary variants via C–C bond formation is made challenging by the acidic nature of the stereocenter. 3,4 This has recently been addressed via transition metal-catalyzed asymmetric coupling reactions of α-bromo ketones to aryl organometallic reagents 5a,b , benzylic bromides to acyl chlorides 5c , and benzylic zinc reagents to thioesters 5d ; additionally, chiral Lewis acid-catalyzed insertion of aryldiazoalkanes into aldehyde C–H bonds has also been described. 5e Despite this progress, complementary catalytic methods for preparing chiral tertiary α-aryl dialkyl ketones from abundant and stable functional groups remain in high demand.…”

Nickel‐Catalyzed Coupling of Arylzinc Halides with Thioesters

“…[4] The FR has certain advantages for synthetic chemists over acylation reactions using Grignard reagents. [6] Besides Pd/ Ca nd the originally employed [PdCl 2 (PPh 3 ) 2 ], the efficiency of phosphine-free Pd 2 dba 3 was demonstrated. [5] Moderne xtensions of the FR are continuouslyb eing developed, such as the enantioconvergent variant based on ad ynamic kinetic resolution of racemic benzylic zinc reagents by chiral catalysts.…”