title: Computational explorations of mechanisms and ligand-directed selectivities of copper-catalyzed Ullmann-type reactions.
abstract: Computational investigations of ligand-directed selectivities in Ullmann-type coupling reactions of methanol and methylamine with iodobenzene by beta-diketone- and 1,10-phenanthroline-ligated Cu(I) complexes are reported. Density functional theory calculations using several functionals were performed on both the nucleophile formation and aryl halide activation steps of these reactions. The origin of ligand-directed selectivities in N- versus O-arylation reactions as described in a previous publication (J. Am. Chem. Soc. 2007, 129, 3490-3491) were studied and explained. The selectivities observed experimentally are derived not from initial Cu(I)(nucleophile) complex formation but from the subsequent steps involving aryl halide activation. The arylation may occur via single-electron transfer (SET) or iodine atom transfer (IAT), depending on the electron-donating abilities of the ligand and nucleophile. Mechanisms involving either oxidative addition/reductive elimination or sigma-bond metathesis are disfavored. SET mechanisms are favored in reactions promoted by the beta-diketone ligand; N-arylation is predicted to be favored in these cases, in agreement with experimental results. The phenanthroline ligand promotes O-arylation reactions via IAT mechanisms in preference to N-arylation reactions, which occur via SET mechanisms; this result is also in agreement with experimental results.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Gavin O
authors.initials: GO
authors.lastname: Jones
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buchwald
mesh_terms: D002384:Catalysis; D003198:Computer Simulation; D003300:Copper / Q000737:chemistry*; D007462:Iodobenzenes / Q000737:chemistry*; D008024:Ligands; D000432:Methanol / Q000737:chemistry*; D008744:Methylamines / Q000737:chemistry*; D008956:Models, Chemical; D010618:Phenanthrolines / Q000737:chemistry*
chemical_list: D007462:Iodobenzenes; D008024:Ligands; D008744:Methylamines; D010618:Phenanthrolines; D003300:Copper; C031905:iodobenzene; C027451:methylamine; C025205:1,10-phenanthroline; D000432:Methanol
references.citation: J Am Chem Soc. 2001 Aug 8;123(31):7727-9
references.pmid: 11481007
references.citation: Phys Rev B Condens Matter. 1988 Jan 15;37(2):785-789
references.pmid: 9944570
references.citation: Chemistry. 2004 Nov 5;10(22):5607-22
references.pmid: 15457520
references.citation: Chem Commun (Camb). 2004 Sep 7;(17):1994-5
references.pmid: 15340638
references.citation: Chem Rev. 2008 Jul;108(7):2180-237
references.pmid: 18620366
references.citation: J Am Chem Soc. 2008 Sep 24;130(38):12762-74
references.pmid: 18761460
references.citation: Org Lett. 2001 Dec 27;3(26):4315-7
references.pmid: 11784206
references.citation: J Am Chem Soc. 2008 Jul 30;130(30):9971-83
references.pmid: 18597458
references.citation: Angew Chem Int Ed Engl. 2010 Mar 15;49(12):2185-9
references.pmid: 20198667
references.citation: J Am Chem Soc. 2002 Oct 2;124(39):11684-8
references.pmid: 12296734
references.citation: Org Lett. 2002 Feb 21;4(4):581-4
references.pmid: 11843596
references.citation: Org Lett. 2002 Oct 17;4(21):3703-6
references.pmid: 12375923
references.citation: J Am Chem Soc. 2007 Nov 14;129(45):13879-86
references.pmid: 17941636
references.citation: J Am Chem Soc. 2007 Mar 28;129(12):3490-1
references.pmid: 17341083
references.citation: J Am Chem Soc. 2006 Jul 12;128(27):8742-3
references.pmid: 16819863
references.citation: J Am Chem Soc. 2009 Jan 14;131(1):78-88
references.pmid: 19072233
references.citation: Org Lett. 2000 May 4;2(9):1333-6
references.pmid: 10810741
references.citation: Chemistry. 2008;14(20):6037-9
references.pmid: 18494009
references.citation: J Am Chem Soc. 2005 Mar 30;127(12):4120-1
references.pmid: 15783164
references.citation: Org Lett. 2003 Mar 20;5(6):793-6
references.pmid: 12633073
references.citation: J Am Chem Soc. 2008 Jul 23;130(29):9196-7
references.pmid: 18582057
references.citation: Org Lett. 2006 Nov 23;8(24):5609-12
references.pmid: 17107084
references.citation: Org Lett. 2003 Jul 10;5(14):2453-5
references.pmid: 12841753
references.citation: J Am Chem Soc. 2009 Dec 2;131(47):17423-9
references.pmid: 19899753
references.citation: J Am Chem Soc. 2002 Jun 26;124(25):7421-8
references.pmid: 12071751
references.citation: J Comput Chem. 2003 Apr 30;24(6):669-81
references.pmid: 12666158