title: Tetramethyleneethane Equivalents: Recursive Reagents for Serialized Cycloadditions.
abstract: New reactions and reagents that allow for multiple bond-forming events per synthetic operation are required to achieve structural complexity and thus value with step-, time-, cost-, and waste-economy. Here we report a new class of reagents that function like tetramethyleneethane (TME), allowing for back-to-back [4 + 2] cycloadditions, thereby amplifying the complexity-increasing benefits of Diels-Alder and metal-catalyzed cycloadditions. The parent recursive reagent, 2,3-dimethylene-4-trimethylsilylbutan-1-ol (DMTB), is readily available from the metathesis of ethylene and THP-protected 4-trimethylsilylbutyn-1-ol. DMTB and related reagents engage diverse dienophiles in an initial Diels-Alder or metal-catalyzed [4 + 2] cycloaddition, triggering a subsequent vinylogous Peterson elimination that recursively generates a new diene for a second cycloaddition. Overall, this multicomponent catalytic cascade produces in one operation carbo- and heterobicyclic building blocks for the synthesis of a variety of natural products, therapeutic leads, imaging agents, and materials. Its application to the three step synthesis of a new solvatochromic fluorophore, N-ethyl(6-N,N-dimethylaminoanthracene-2,3-dicarboximide) (6-DMA), and the photophysical characterization of this fluorophore are described.
authors.affiliation: Department of Chemistry, Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305-5080, United States.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Wender
authors.affiliation: Department of Chemistry, Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305-5080, United States.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Jeffreys
authors.affiliation: Department of Chemistry, Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305-5080, United States.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Raub
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000873:Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D061565:Cycloaddition Reaction / Q000191:economics / Q000379:methods*; D004980:Ethane / Q000031:analogs & derivatives* / Q000737:chemistry; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D008670:Metals / Q000737:chemistry
chemical_list: D000475:Alkenes; D000873:Anthracenes; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D008670:Metals; C527958:tetramethyleneethane; D004980:Ethane