Tetramethyleneethane Equivalents: Recursive
Reagents for Serialized Cycloadditions
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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, <i>N</i>-ethyl(6-<i>N</i>,<i>N</i>-dimethylaminoanthracene-2,3-dicarboximide) (6-DMA), and
the photophysical characterization of this fluorophore are described