Abstract
The first (4 + 1)-annulation of o-quinone methides with α-branched allenoates as C1 synthons has been developed. This operationally simple protocol gives access to highly functionalized dihydrobenzofurans in an unprecedented fashion with excellent diastereoselectivities and high yields.
Highlights
Quinone methides (QMs), either preformed or generated in situ, have emerged as a versatile class of building blocks for transformations over recent years.[1]
Our group has very recently developed a highly enantioselective (4 + 1)-annulation protocol by reacting in situ generated chiral ammonium ylides with in situ generated o-QMs 1.5e In ongoing investigations aimed at the introduction of new synthesis methodologies that use o-QMs as available acceptors for cyclization reactions, we have tested the use of simple α-substituted allenoates 7 for the reaction with quinone methide precursors 3 (Scheme 1B)
We initially reasoned that this reaction should give the highly functionalized (4 + 2)-cyclization products 6
Summary
AAll reactions were carried out using 0.1 mmol of 7a at room temperature for 20 h in dry and degassed solvents. bIsolated yields. Addition of B to the in situ formed o-QM 1 gives the betaine C as the primary addition product This intermediate could either undergo a ring-closure to access the (4 + 3)-annulation product 9 (dashed blue pathway) or, alternatively, undergo rapid proton-transfer/double-bond migration reactions5e toward the intermediate D, which can undergo a 5-exo-trig cyclization to yield product 8 . On the other hand, when we carried out the reaction with nondeuterated 7a in CD2Cl2 we observed a small amount of Dincorporation in the methyl group of product 8a (detected by 2H NMR spectroscopy) All these results clearly show that intra- and intermolecular proton transfers are very possible on these targets/intermediates, making the proposed isomerizations from A/A′ to B and C to D very likely. Analytical details, and NMR spectra of all the compounds (PDF)
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