Herein described is a strategy for promoting thermodynamically unfavorable [3,3] Cope rearrangements. 3,3-Dicyano-1,5-dienes that are resistant to the thermal rearrangement can be promoted under reductive conditions. The reduced Cope products are versatile, bifunctional building blocks.
Systematic
evaluation of 1,5-dienes bearing 3,3-electron-withdrawing
groups and 4-methylation results in the discovery of a Cope rearrangement
for Meldrum’s acid-containing substrates that have unexpectedly
favorable kinetic and thermodynamic profiles. The protocol is quite
general due to a concise and convergent synthesis from abundant starting
materials. Furthermore, products with an embedded Meldrum’s
acid moiety are prepared, which, in turn, can yield complex amides
under neutral conditions. We have now expanded the scope of the reductive
Cope rearrangement, which, via chemoselective reduction, can promote
thermodynamically unfavorable [3,3] sigmatropic rearrangements of
3,3-dicyano-1,5-dienes to form reduced Cope rearrangement products.
The Cope rearrangement is found to be stereospecific and can yield
enantioenriched building blocks when chiral, nonracemic 1,3-disubstituted
allylic electrophiles are utilized. We expand further the use of Cope
rearrangements for the synthesis of highly valuable building blocks
for complex- and drug-like molecular synthesis.
Polyfunctionalized
cyclohexanes are privileged scaffolds in drug
discovery. Reported herein is a method for synthesizing 1,2,4-trifunctionalized
cyclohexanes via diastereoselective reductive Cope rearrangement.
The scaffolds obtained can be derivatized by orthogonal functional
group interconversion to cyclohexanes bearing a 1-amide, 2-branched
arylallyl, and variable 4-functional group.
An asymmetric allylic alkylation/Cope rearrangement (AAA/[3,3]) capable of stereoselectively constructing vicinal stereocenters has been developed. Strategically integrated 4-methylation on the 3,3-dicyano-1,5-diene controls stereoselectivity and drives Cope rearrangement equilibrium in the...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.