title: Structural complexity through multicomponent cycloaddition cascades enabled by dual-purpose, reactivity regenerating 1,2,3-triene equivalents.
abstract: Multicomponent reactions allow for more bond-forming events per synthetic operation, enabling more step- and time-economical conversion of simple starting materials to complex and thus value-added targets. These processes invariably require that reactivity be relayed from intermediate to intermediate over several mechanistic steps until a termination event produces the final product. Here, we report a multicomponent process in which a novel 1,2,3-butatriene equivalent (TMSBO: TMSCH2C≡CCH2OH) engages chemospecifically as a two-carbon alkyne component in a metal-catalysed [5 + 2] cycloaddition with a vinylcyclopropane to produce an intermediate cycloadduct. Under the reaction conditions, this intermediate undergoes a remarkably rapid 1,4-Peterson elimination, producing a reactive four-carbon diene intermediate that is readily intercepted in either a metal-catalysed or thermal [4 + 2] cycloaddition. TMSBO thus serves as an yne-to-diene transmissive reagent coupling two powerful and convergent cycloadditions--the homologous Diels-Alder and Diels-Alder cycloadditions--through a vinylogous Peterson elimination, and enabling flexible access to diverse polycycles.
authors.affiliation: Department of Chemistry, Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305-5080, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Wender
authors.affiliation: 1] Department of Chemistry, Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305-5080, USA [2].
authors.forename: Dennis N
authors.initials: DN
authors.lastname: Fournogerakis
authors.affiliation: 1] Department of Chemistry, Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305-5080, USA [2].
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Jeffreys
authors.affiliation: 1] Department of Chemistry, Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305-5080, USA [2].
authors.forename: Ryan V
authors.initials: RV
authors.lastname: Quiroz
authors.affiliation: Department of Chemistry, Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305-5080, USA.
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Inagaki
authors.affiliation: Department of Chemistry, Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305-5080, USA.
authors.forename: Magnus
authors.initials: M
authors.lastname: Pfaffenbach
mesh_terms: D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D015394:Molecular Structure
chemical_list: D000480:Alkynes
references.citation: Org Lett. 2007 Dec 6;9(25):5163-6
references.pmid: 17999510
references.citation: J Am Chem Soc. 2011 Nov 16;133(45):18050-3
references.pmid: 21999462
references.citation: J Org Chem. 2011 May 6;76(9):3122-30
references.pmid: 21438546
references.citation: J Am Chem Soc. 2007 Feb 7;129(5):1050-1
references.pmid: 17263384
references.citation: Nature. 2009 Jul 9;460(7252):197-201
references.pmid: 19587760
references.citation: Chem Biol Drug Des. 2009 Jul;74(1):16-24
references.pmid: 19519740
references.citation: Org Lett. 2003 Mar 6;5(5):669-72
references.pmid: 12605486
references.citation: Chem Rev. 2012 Mar 14;112(3):1310-43
references.pmid: 22040177
references.citation: Org Lett. 2003 Jan 9;5(1):59-61
references.pmid: 12509890
references.citation: Med Res Rev. 2000 Jul;20(4):304-22
references.pmid: 10861729
references.citation: Chemistry. 2011 Jun 20;17(26):7162-6
references.pmid: 21574194
references.citation: Angew Chem Int Ed Engl. 2012 Mar 5;51(10):2298-338
references.pmid: 22337341
references.citation: Angew Chem Int Ed Engl. 2002 Dec 2;41(23):4550-3
references.pmid: 12458535
references.citation: J Antibiot (Tokyo). 1977 Apr;30(4):275-82
references.pmid: 863788
references.citation: Org Lett. 2006 Sep 28;8(20):4649-52
references.pmid: 16986972
references.citation: Pharmacol Res. 2000 Oct;42(4):373-81
references.pmid: 10987998
references.citation: Nat Prod Rep. 2010 Apr;27(4):489-98
references.pmid: 20336234