title: 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.
authors.affiliation: Department of Chemistry, National Taiwan Normal University, No. 88, Section 4, Tingzhou Road, Taipei 11677, Taiwan (RoC).
authors.forename: Balraj
authors.initials: B
authors.lastname: Gopula
authors.affiliation: Department of Chemistry, National Taiwan Normal University, No. 88, Section 4, Tingzhou Road, Taipei 11677, Taiwan (RoC).
authors.forename: Shu-Han
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Chemistry, National Taiwan Normal University, No. 88, Section 4, Tingzhou Road, Taipei 11677, Taiwan (RoC).
authors.forename: Ting-Shen
authors.initials: TS
authors.lastname: Kuo
authors.affiliation: Department of Chemistry, Tamkang University, New Taipei City, 25137, Taiwan (RoC). jchsieh@mail.tku.edu.tw.
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Hsieh
authors.affiliation: ScinoPharm Taiwan, No. 1, Nan-Ke Eighth Road, Tainan Science-Based Industrial Park, Shan-Hua, Tainan County 74144, Taiwan (RoC).
authors.forename: Ping-Yu
authors.initials: PY
authors.lastname: Wu
authors.affiliation: ScinoPharm Taiwan, No. 1, Nan-Ke Eighth Road, Tainan Science-Based Industrial Park, Shan-Hua, Tainan County 74144, Taiwan (RoC). Julian.Henschke@scinopharm.com.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Henschke
authors.affiliation: Department of Chemistry, National Taiwan Normal University, No. 88, Section 4, Tingzhou Road, Taipei 11677, Taiwan (RoC). hlw@ntnu.edu.tw.
authors.forename: Hsyueh-Liang
authors.initials: HL
authors.lastname: Wu
mesh_terms: D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D008024:Ligands; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D012238:Rhodium / Q000737:chemistry; D013237:Stereoisomerism; D013388:Succinimides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001897:Boronic Acids; D008024:Ligands; D008301:Maleimides; D011759:Pyrrolidines; D013388:Succinimides; D012238:Rhodium; C032519:pyrrolidine
keywords: chiral ligands; conjugate addition; enantioselectivity; pyrrolidine; rhodium