title: Direct bis-arylation of cyclobutanecarboxamide via double C-H activation: an auxiliary-aided diastereoselective Pd-catalyzed access to trisubstituted cyclobutane scaffolds having three contiguous stereocenters and an all-cis stereochemistry.
abstract: An auxiliary-aided Pd-catalyzed highly diastereoselective double C-H activation and direct bis-arylation of methylene C(sp(3))-H bonds of cyclobutanecarboxamides and the syntheses of several novel trisubstituted cyclobutanecarboxamide scaffolds having an all-cis stereochemistry are reported. Extensive screening of various auxiliaries and reaction conditions was performed to firmly establish the optimized reaction conditions required for effecting the mono- or double C-H arylation of cyclobutanecarboxamides. The auxiliary-attached cyclobutanecarboxamides 15a, 15g, and 15h, prepared from the auxiliaries such as, 8-aminoquinoline, 2-(methylthio)aniline, and N',N'-dimethylethane-1,2-diamine were found to undergo an efficient direct bis-arylation. The Pd-catalyzed arylation reaction of N-(quinolin-8-yl)cyclobutanecarboxamide 15a with one equivalent or more of aryl iodides, afforded the corresponding bis-arylated cyclobutanecarboxamides 16a-y. Nevertheless, the Pd-catalyzed arylation of 15a with just 0.5 equiv of the aryl iodides 13a, 13b, 13e, and 13m, selectively gave the corresponding monoarylated cyclobutanecarboxamides 17a-17d. The Pd-catalyzed arylation of 15g or 15h with one equivalent or more of aryl iodides afforded the bis-arylated cyclobutanecarboxamides 19a-19c and 21a-21m, respectively. However, the Pd-catalyzed arylations of compounds 15g or 15h with just 0.5 equiv of aryl iodides were ineffective. The stereochemistry of compounds obtained in this work was unambiguously assigned from the X-ray structures of representative products.
authors.affiliation: Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali , Manauli P.O., Sector 81, SAS Nagar, Mohali, Knowledge City, Punjab 140306, India.
authors.forename: Ramarao
authors.initials: R
authors.lastname: Parella
authors.forename: Bojan
authors.initials: B
authors.lastname: Gopalakrishnan
authors.forename: Srinivasarao Arulananda
authors.initials: SA
authors.lastname: Babu
mesh_terms: D002384:Catalysis; D003503:Cyclobutanes / Q000737:chemistry*; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D003503:Cyclobutanes; D010165:Palladium