A reaction sequence involving the 1,6-conjugate addition of a nucleophile to a dienyl diketone followed by Nazarov cyclization is described. Several nucleophiles are identified as competent initiators for the sequence. A different reaction outcome is is observed when catalytic amounts of nucleophile are employed, involving elimination of the nucleophile after the electrocyclization.
The
1,6-conjugate addition of nucleophiles to dienyl diketones
produces either cyclopentenone or 2H-pyran products
with high selectivity through either Nazarov (4π) or 6π
electrocyclization, respectively. The outcome of the reaction is dependent
upon the nature of the nucleophile used. Nucleophiles that are anionic
or easily deprotonated exclusively produce cyclopentenones via Nazarov
cyclization, whereas the neutral nucleophile DABCO promotes 6π
cyclization to afford 2H-pyrans. Experimental evidence
is presented for both retro-4π and -6π electrocyclization
in these systems, lending support to the bifurcated mechanistic hypothesis
proposed for these cyclizations.
Dienyl diketones containing tethered acetates selectively undergo two different 1,6-conjugate addition-initiated cyclization cascades. One is a 1,6-conjugate addition/cyclization sequence with incorporation of the nucleophile, and the other is catalyzed by DABCO and is thought to proceed via a cyclic acetoxonium intermediate. The reaction behavior of substrates lacking the tethered acetate was also studied. The scope of both types of cyclization cascades, the role of the amine additive, and the factors controlling reactivity and selectivity in the two different reaction pathways is discussed.
Palladium-catalyzed
oxidative cyclization of alkenols provides
a convenient entry into cyclic ethers but typically proceeds with
little or no diastereoselectivity for cyclization of trisubstituted
olefins to form tetrahydrofurans due to the similar energies of competing
5-membered transition-state conformations. Herein, a new variant of
this reaction has been developed in which a PdCl2/1,4-benzoquinone
catalyst system coupled with introduction of a hydrogen-bond acceptor
in the substrate enhances both diastereoselectivity and reactivity.
Cyclization occurs with 5-exo Markovnikov regioselectivity.
Mechanistic and computational studies support an anti-oxypalladation pathway in which intramolecular hydrogen bonding
increases the nucleophilicity of the alcohol and enforces conformational
constraints that enhance diastereoselectivity. The cyclization is
followed by a tandem redox-relay process that provides versatile side-chain
functionalities for further derivatization.
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