title: Brønsted acid cocatalysts in photocatalytic radical addition of α-amino C-H bonds across Michael acceptors.
abstract: In marked contrast to the variety of strategies available for oxidation and nucleophilic functionalization of methylene groups adjacent to amines, relatively few approaches for modification of this position with electrophilic reaction partners have been reported. In the course of an investigation of the reactions of photogenerated α-amino radicals with electrophiles, we made the surprising observation that the efficiency of radical photoredox functionalization of N-aryl tetrahydroisoquinolines is dramatically increased in the presence of a Brønsted acid cocatalyst. Optimized conditions provide high yields and efficient conversion to radical addition products for a range of structurally modified tetrahydroisoquinolines and enones using convenient household light sources and commercially available Ru(bpy)3Cl2 as a photocatalyst. Our investigations into the origins of this unexpected additive effect have demonstrated that the carbon-carbon bond-forming step is accelerated by TFA and is a rare example of Brønsted acid catalysis in radical addition reactions. Moreover, a significant conclusion arising from these studies is the finding that product formation is dominated by radical chain processes and not by photocatalyst turnover. Together, these findings have important implications for the future design and mechanistic evaluation of photocatalytic radical processses.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Ruiz Espelt
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wiensch
authors.forename: Tehshik P
authors.initials: TP
authors.lastname: Yoon
mesh_terms: D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D055668:Photochemical Processes; D012428:Ruthenium / Q000737:chemistry*; D044005:Tetrahydroisoquinolines / Q000737:chemistry*
chemical_list: D009942:Organometallic Compounds; D044005:Tetrahydroisoquinolines; D002244:Carbon; D012428:Ruthenium
references.citation: J Am Chem Soc. 2012 Feb 22;134(7):3338-41
references.pmid: 22296639
references.citation: J Am Chem Soc. 2008 Oct 1;130(39):12886-7
references.pmid: 18767798
references.citation: J Am Chem Soc. 2010 Feb 10;132(5):1464-5
references.pmid: 20070079
references.citation: J Am Chem Soc. 2008 Aug 20;130(33):11005-12
references.pmid: 18646852
references.citation: J Am Chem Soc. 2011 Nov 23;133(46):18566-9
references.pmid: 22047138
references.citation: J Am Chem Soc. 2012 May 30;134(21):8875-84
references.pmid: 22486313
references.citation: J Am Chem Soc. 2005 Mar 23;127(11):3672-3
references.pmid: 15771482
references.citation: J Am Chem Soc. 2011 Feb 9;133(5):1162-4
references.pmid: 21214249
references.citation: Synlett. 2012 Aug;23(13):1851-1856
references.pmid: 23419975
references.citation: J Am Chem Soc. 2011 May 25;133(20):8014-27
references.pmid: 21539314
references.citation: Org Lett. 2012 Jan 6;14(1):94-7
references.pmid: 22148974
references.citation: Angew Chem Int Ed Engl. 2012 Jul 9;51(28):6828-38
references.pmid: 22711502
references.citation: J Am Chem Soc. 2011 Feb 9;133(5):1260-2
references.pmid: 21204541
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):8928-33
references.pmid: 16754869
references.citation: Chemistry. 2012 Aug 13;18(33):10092-142
references.pmid: 22829434
references.citation: Angew Chem Int Ed Engl. 2009;48(52):9785-9
references.pmid: 19946918
references.citation: Angew Chem Int Ed Engl. 1998 Oct 16;37(19):2562-2579
references.pmid: 29711628
references.citation: Org Lett. 2012 Feb 3;14(3):672-5
references.pmid: 22260623
references.citation: J Am Chem Soc. 2004 Sep 29;126(38):11810-1
references.pmid: 15382913
references.citation: Chem Sci. 2011 Jan 1;2(11):2115-2119
references.pmid: 22121471
references.citation: Chem Soc Rev. 2007 Jul;36(7):1069-84
references.pmid: 17576475
references.citation: Chem Soc Rev. 2011 Jan;40(1):102-13
references.pmid: 20532341
references.citation: J Am Chem Soc. 1986 Sep 1;108(19):6063-5
references.pmid: 22175386
references.citation: Chem Soc Rev. 2012 Dec 7;41(23):7687-97
references.pmid: 22869017
references.citation: Acc Chem Res. 2009 Feb 17;42(2):335-44
references.pmid: 19220064
references.citation: Chem Rev. 2013 Jul 10;113(7):5322-63
references.pmid: 23509883
references.citation: J Am Chem Soc. 2012 Jun 6;134(22):9034-7
references.pmid: 22624669
references.citation: Acc Chem Res. 2001 Jul;34(7):523-33
references.pmid: 11456470
references.citation: J Am Chem Soc. 2009 Aug 12;131(31):10875-7
references.pmid: 19722670
references.citation: Nat Chem. 2010 Jul;2(7):527-32
references.pmid: 20571569
references.citation: J Org Chem. 2009 Oct 2;74(19):7464-9
references.pmid: 19731925
references.citation: Chem Rev. 2003 Aug;103(8):3263-96
references.pmid: 12914498
references.citation: Chem Commun (Camb). 2010 Sep 14;46(34):6285-7
references.pmid: 20694243
references.citation: J Org Chem. 2012 Feb 17;77(4):1617-22
references.pmid: 22283525
references.citation: Science. 2008 Oct 3;322(5898):77-80
references.pmid: 18772399
references.citation: J Am Chem Soc. 2013 Feb 6;135(5):1823-9
references.pmid: 23330701