Direct Catalytic Enantioselective Benzylation from Aryl Acetic Acids

Abstract

We demonstrate that metal-catalyzed enantioselective benzylation reactions of allylic electrophiles can occur directly from aryl acetic acids. The reaction proceeds via a pathway in which decarboxylation is the terminal event, occurring after stereoselective carbon−carbon bond formation. This mechanistic feature enables enantioselective benzylation without the generation of a highly basic nucleophile. Thus, the process has broad functional group compatibility that would not be possible employing established protocols.

Iridium‐Catalyzed Asymmetric Allylic Aromatization Reaction

“…[7e, 11] Gratifyingly,when Yb(OTf) 3 , In(OTf) 3 ,a nd Fe(OTf) 2 were tested, the reactions worked better,a ffording 3a in 58-70 %y ields.N ext, as eries of solvents were evaluated with Fe(OTf) 2 as the promoter, and DCE was identified as the optimal choice (entries [6][7][8][9]. With an Ir complex derived from [Ir(cod)Cl] 2 (3 mol %) and the Carreira (P,o lefin) ligand (S)-L1 (12 mol %) as the catalyst, and diphenylsulfonimide as the promoter for the electrophile,the reaction proceeded in 1,2-dichloroethane (DCE) and afforded the desired product 3a in 30 %yield (entry 1).…”

“…[4] Pioneering contributions from the groups of Tr ost [4a] and Walsh [4e] independently demonstrated Pd-catalyzed asymmetric allylic alkylation reactions of 2-picoline and toluene derivatives,respectively ( Figure 1). [6] Despite remarkable progress in this area, most of these reactions suffer from either requiring additional operations (such as addition/removal of the activating reagents and removal of the carboxylic group), limited types of benzylic nucleophiles,o rh arsh conditions requiring strong base.I na ddition, the reactions typically utilize activated allylic substrates,t hus generating stoichiometric quantities of waste material. [5] Notably,parallel works from the groups of Yu and Lundgren achieved either Pd-or Ircatalyzed asymmetric allylic alkylation reactions with benzylic nucleophiles by photoredox radical process and adecarboxylative strategy,r espectively.…”

Iridium‐Catalyzed Asymmetric Allylic Aromatization Reaction

“…Zn(OTf) 2 ,which has been successfully employed in Ir-catalyzed AAA reactions,w as ineffective in this reaction. [7e, 11] Gratifyingly,when Yb(OTf) 3 , In(OTf) 3 ,a nd Fe(OTf) 2 were tested, the reactions worked better,a ffording 3a in 58-70 %y ields.N ext, as eries of solvents were evaluated with Fe(OTf) 2 as the promoter, and DCE was identified as the optimal choice (entries [6][7][8][9]. Since the reaction generates 1equivalent of water as aside product, the potential effects of various molecular sieves were considered (entries [10][11][12].…”

“…[5] Notably,parallel works from the groups of Yu and Lundgren achieved either Pd-or Ircatalyzed asymmetric allylic alkylation reactions with benzylic nucleophiles by photoredox radical process and adecarboxylative strategy,r espectively. [6] Despite remarkable progress in this area, most of these reactions suffer from either requiring additional operations (such as addition/removal of the activating reagents and removal of the carboxylic group), limited types of benzylic nucleophiles,o rh arsh conditions requiring strong base.I na ddition, the reactions typically utilize activated allylic substrates,t hus generating stoichiometric quantities of waste material. Meanwhile,the reactions involving benzylic nucleophiles derived from five-membered aromatic compounds are still much less developed.…”

Enantio- and Diastereoselective Suzuki-Miyaura Coupling with Racemic Bicycles

“…[9] Using non-stabilized nucleophiles (pK a > 25) in enantioconvergent asymmetric allylic alkylation was found to be much more challenging and has only recently been reported. [10][11][12] Building on this work, we reported highly enantioselective rhodium-catalyzed Suzuki-Miyaura-type couplings between racemic cyclic allylic halides with sp 2 -hybridized boronic acid derivatives. [13] These procedures allow the coupling of functionalized and heterocyclic coupling partners,apowerful strategy for drug development, [14] and are practical as they share many of the same features that make standard Suzuki-Miyaura reactions popular;t hey use experimentally convenient and often commercially available boronic acid derivatives.…”