N-heterocyclic carbene-catalyzed conjugate additions of alcohols.
An efficient intermolecular conjugate addition of alcohols to activated alkenes catalyzed by N-heterocyclic carbenes has been developed. With 5 mol % of the free carbene derived from IMes·HCl, unsaturated ketones and esters are competent substrates, and a variety of primary and secondary alcohols can be employed as the nucleophile. No oligomerization is observed under these mild conditions for effective hydroalkoxylation. In addition to reactions with activated alkenes, IMes catalyzes the formation of vinyl ethers through the 1,4-addition of alcohols to ynones and promotes tandem conjugate addition/Michael cascade reactions. Preliminary data support a Brønsted base mechanism with the free carbene.
Phillips
Eric M
EM
Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Chemistry of Life Processes Institute, Northwestern University, Silverman Hall, 2145 Sheridan Road, Evanston, Illinois 60208, USA.
Riedrich
Matthias
M
Scheidt
Karl A
KA
D000438:Alcohols / Q000737:chemistry*; D002384:Catalysis; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry
D000438:Alcohols; D006571:Heterocyclic Compounds; C030011:carbene; D008697:Methane
Org Lett. 2009 Jan 1;11(1):105-8
19049403
Angew Chem Int Ed Engl. 2009;48(31):5701-4
19557777
Acc Chem Res. 2004 Aug;37(8):534-41
15311952
J Am Chem Soc. 2004 Apr 7;126(13):4366-74
15053626
Aldrichimica Acta. 2009;42(3):55-66
21072130
Org Lett. 2005 Mar 3;7(5):905-8
15727471
Chem Rev. 2007 Dec;107(12):5606-55
17956132
J Org Chem. 2007 Sep 14;72(19):7466-8
17705547
J Am Chem Soc. 2006 Jul 5;128(26):8418-20
16802805
J Am Chem Soc. 2004 Mar 3;126(8):2314-5
14982429
J Am Chem Soc. 2006 Feb 8;128(5):1472-3
16448117
Angew Chem Int Ed Engl. 2003 Sep 15;42(35):4241-4
14502746
Org Lett. 2008 Feb 21;10(4):565-7
18211073
J Am Chem Soc. 2007 May 2;129(17):5334-5
17407298
J Am Chem Soc. 2009 Dec 23;131(50):18028-9
20000857
Org Lett. 2005 Jun 9;7(12):2453-6
15932221
Org Lett. 2007 Jun 21;9(13):2581-4
17539656
J Am Chem Soc. 2008 Mar 5;130(9):2740-1
18260665
J Am Chem Soc. 2010 Apr 21;132(15):5345-7
20345186
Angew Chem Int Ed Engl. 2005 Nov 25;44(46):7506-10
16302182
Org Lett. 2002 Oct 17;4(21):3583-6
12375893
Inorg Chem. 2009 Nov 2;48(21):9971-3
19813724
J Am Chem Soc. 2002 May 22;124(20):5757-61
12010050
Org Lett. 2002 Oct 17;4(21):3587-90
12375894
J Org Chem. 2002 May 31;67(11):3555-60
12027665
Angew Chem Int Ed Engl. 2007;46(17):2988-3000
17348057
J Org Chem. 2007 Sep 28;72(20):7790-3
17725367
J Am Chem Soc. 2003 Jul 23;125(29):8696-7
12862443
Org Lett. 2010 Jun 18;12(12):2830-3
20469924
Angew Chem Int Ed Engl. 2008;47(9):1560-638
18236505