Direct Synthesis of Chiral 3‐Arylsuccinimides by Rhodium‐Catalyzed Enantioselective Conjugate Addition of Arylboronic Acids to Maleimides

Abstract

Chiral rhodium catalysts comprising 2,5-diaryl- substituted bicyclo[2.2.1]diene ligands L1-L10 were utilized in the enantioselective 1,4-addition reaction of arylboronic acids to N-substituted maleimides. In the presence of 2.5 mol % of Rh(I) /L2, enantioenriched conjugate addition adducts were isolated in 72-99 % yields with 86-98 % ee. This protocol offers a convenient method to access a variety of 3-arylsuccinimides in a highly enantioselective manner. Maleimides with readily cleavable N-protecting groups were tolerated enabling the synthesis of useful synthetic intermediates. Pyrrolidine 4, a biologically active compound, and pyrrolidine 5, an ent-precursor to an HSD-1 inhibitor, were synthesized to demonstrate the utility of this method.

Chiral Diene Ligands in Asymmetric Catalysis

“…Maleimides 101 have also been investigated for the rhodium-catalyzed asymmetric addition of arylboronic acids. Using ( R,R )- L2e and L4a under similar catalytic conditions gave aryl-substituted succinimides 102 with high enantioselectivity (Scheme b).…”

Synthesis of Quaternary‐Carbon‐Containing β2,2‐Amino Acids by the RhI‐Catalyzed Enantioselective Arylation of α‐Substituted β‐Nitroacrylates

“…The majority of the common bases that were tested afforded comparable yields (44–47 %) and ee values (94–95 %) of 3 ac , whereas NaHCO 3 (entry 3) and KOH (entry 8) provided moderately improved yields of 56 and 55 %, respectively (Table , entries 1–8). Although amine bases have proven optimal in some addition reactions of boronic acids to Michael acceptors, no reaction was observed when Et 3 N was employed in the present study (entry 9). However, in terms of the ee values no base additive provided better results than was achieved with KHF 2 (Table , entry 6), and therefore this was used in subsequent tests.…”

Activation, Deactivation and Reversibility Phenomena in Homogeneous Catalysis: A Showcase Based on the Chemistry of Rhodium/Phosphine Catalysts

“…The nature of the species that are actually present under stationary conditions cannot be predicted a priori and which one, among these, is responsible for the catalytic activity may be difficult to establish. It should also be noted that even the starting diolefin precursor can be catalytically active [77][78][79][80][81][82][83][84][85]. Because selectivity is mostly determined by the type of ligand coordinated to the metal, if the diolefin precursor is not completely converted, selectivity will be negatively affected.…”