title: Suzuki-Miyaura cross-coupling of unprotected, nitrogen-rich heterocycles: substrate scope and mechanistic investigation.
abstract: The Suzuki-Miyaura cross-coupling of unprotected, nitrogen-rich heterocycles using precatalysts P1 or P2 is reported. The procedure allows for the reaction of variously substituted indazole, benzimidazole, pyrazole, indole, oxindole, and azaindole halides under mild conditions in good to excellent yields. Additionally, the mechanism behind the inhibitory effect of unprotected azoles on Pd-catalyzed cross-coupling reactions is described based on evidence gained through experimental, crystallographic, and theoretical investigations.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: M Alexander
authors.initials: MA
authors.lastname: Düfert
authors.forename: Kelvin L
authors.initials: KL
authors.lastname: Billingsley
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buchwald
mesh_terms: D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory
chemical_list: D006571:Heterocyclic Compounds; D047428:Protein Kinase Inhibitors; D009584:Nitrogen
references.citation: Org Lett. 2012 Jan 6;14(1):170-3
references.pmid: 22182186
references.citation: Mini Rev Med Chem. 2005 Oct;5(10):869-78
references.pmid: 16250831
references.citation: Chem Sci. 2013;4:916-920
references.pmid: 23667737
references.citation: Chem Rev. 2006 Nov;106(11):4644-80
references.pmid: 17091931
references.citation: Angew Chem Int Ed Engl. 2012 May 7;51(19):4710-3
references.pmid: 22473747
references.citation: Org Lett. 2008 Jul 3;10(13):2765-8
references.pmid: 18529011
references.citation: J Med Chem. 2010 Apr 22;53(8):3005-12
references.pmid: 20146479
references.citation: Chem Soc Rev. 2007 Jul;36(7):1120-32
references.pmid: 17576479
references.citation: J Am Chem Soc. 2008 May 28;130(21):6686-7
references.pmid: 18447360
references.citation: Angew Chem Int Ed Engl. 2013 Jan 7;52(2):615-9
references.pmid: 23172689
references.citation: Angew Chem Int Ed Engl. 2011 Jul 18;50(30):6722-37
references.pmid: 21618370
references.citation: Beilstein J Org Chem. 2011;7:442-95
references.pmid: 21647262
references.citation: J Am Chem Soc. 2010 Oct 13;132(40):14073-5
references.pmid: 20858009
references.citation: J Am Chem Soc. 2010 Aug 25;132(33):11416-7
references.pmid: 20681622
references.citation: Bioorg Med Chem Lett. 2005 Nov 15;15(22):5095-9
references.pmid: 16140012
references.citation: J Am Chem Soc. 2011 Feb 23;133(7):2116-9
references.pmid: 21280669
references.citation: Angew Chem Int Ed Engl. 2006 Feb 13;45(8):1282-4
references.pmid: 16425308
references.citation: J Org Chem. 2011 Jun 17;76(12):4930-40
references.pmid: 21526832
references.citation: Bioorg Med Chem. 2012 Nov 1;20(21):6208-36
references.pmid: 23031649
references.citation: Chem Soc Rev. 2012 May 21;41(10):3929-68
references.pmid: 22447100
references.citation: J Med Chem. 2011 May 26;54(10):3451-79
references.pmid: 21504168
references.citation: Chemistry. 2012 May 21;18(21):6616-25
references.pmid: 22511514
references.citation: J Am Chem Soc. 2007 Mar 21;129(11):3358-66
references.pmid: 17326639
references.citation: Org Lett. 2003 Oct 2;5(20):3587-90
references.pmid: 14507179
references.citation: J Med Chem. 2012 Mar 22;55(6):2688-701
references.pmid: 22352782
references.citation: Org Lett. 2012 Aug 17;14(16):4242-5
references.pmid: 22873832
references.citation: Angew Chem Int Ed Engl. 2012 Apr 2;51(14):3314-32
references.pmid: 22287485
references.citation: J Org Chem. 2004 Oct 1;69(20):6812-20
references.pmid: 15387606
references.citation: Chem Soc Rev. 2007 Jul;36(7):1173-93
references.pmid: 17576484
references.citation: Acc Chem Res. 2008 Nov 18;41(11):1461-73
references.pmid: 18620434
references.citation: J Org Chem. 2008 Nov 7;73(21):8422-36
references.pmid: 18834176
references.citation: Science. 2010 Jun 25;328(5986):1679-81
references.pmid: 20576888
references.citation: Chem Commun (Camb). 2004 Sep 7;(17):1922-3
references.pmid: 15340602
references.citation: J Org Chem. 2007 Oct 26;72(22):8543-6
references.pmid: 17910503
references.citation: Inorg Chem. 2000 Mar 6;39(5):975-9
references.pmid: 12526377
references.citation: Chemistry. 2011 Feb 18;17(8):2492-503
references.pmid: 21319240
references.citation: Beilstein J Org Chem. 2011;7:1261-77
references.pmid: 21977211
references.citation: Chemistry. 2010 Jul 19;16(27):7996-8001
references.pmid: 20564295
references.citation: Angew Chem Int Ed Engl. 2007;46(45):8674-8
references.pmid: 17924387
references.citation: Org Lett. 2012 Aug 17;14(16):4266-9
references.pmid: 22853624
references.citation: J Org Chem. 1998 Feb 6;63(3):461-470
references.pmid: 11672034
references.citation: Org Lett. 2010 Oct 15;12(20):4442-5
references.pmid: 20860403
references.citation: Chemistry. 2006 Jun 23;12(19):5142-8
references.pmid: 16628762
references.citation: Chemistry. 2009;15(6):1324-8
references.pmid: 19115290
references.citation: Chem Commun (Camb). 2007 Dec 21;(47):5069-71
references.pmid: 18049756
references.citation: Acc Chem Res. 2008 Nov 18;41(11):1555-64
references.pmid: 18947239
references.citation: J Med Chem. 2011 Apr 28;54(8):2529-91
references.pmid: 21413808
references.citation: Science. 2009 Sep 25;325(5948):1661-4
references.pmid: 19679769