Synthesis of Chiral Diazabicycloalkanes via Organocatalytic aza‐Michael/Aldol Reaction
Fabian Scharinger,
Matthias Weil,
Michael Schnürch
et al.
Abstract:We introduce a strategy for the one‐step synthesis of chiral diazabicycloalkanes that delivers the annulated ring system in a single reaction step. The method entails a direct aza‐Michael/aldol reaction of enals in conjunction with modified oxopropanamides and establishes the chiral center via iminium‐enamine tandem catalysis. For this purpose, we developed simple diphenylethylendiamine frameworks as dual activation organocatalyst, effectively engaging both the substrate and reagent, thus leading to yields of … Show more
“…Melting points (mp) for solid compounds were recorded using a Labindia MR-VIS instrument in open glass capillaries. Compounds 1b , 1c , 1d , 1l , 1m , 2e , and 2k were prepared according to the literature procedure.…”
A general methodology for the asymmetric synthesis of αarylcyclohexeneones from arylacetones and α,β-unsaturated aldehydes catalyzed by diphenylprolinol silyl ether followed by p-TSA-mediated cyclization is developed. A variety of arylacetones and α,β-unsaturated aldehydes were successfully converted to α-arylcyclohexeneones in 34−67% yield, 10:1−100:0 dr, and 81−99% ee. The scalability of this methodology by a gram-scale synthesis and their utility by converting the product to the corresponding epoxide, alcohol, and diol are demonstrated.
“…Melting points (mp) for solid compounds were recorded using a Labindia MR-VIS instrument in open glass capillaries. Compounds 1b , 1c , 1d , 1l , 1m , 2e , and 2k were prepared according to the literature procedure.…”
A general methodology for the asymmetric synthesis of αarylcyclohexeneones from arylacetones and α,β-unsaturated aldehydes catalyzed by diphenylprolinol silyl ether followed by p-TSA-mediated cyclization is developed. A variety of arylacetones and α,β-unsaturated aldehydes were successfully converted to α-arylcyclohexeneones in 34−67% yield, 10:1−100:0 dr, and 81−99% ee. The scalability of this methodology by a gram-scale synthesis and their utility by converting the product to the corresponding epoxide, alcohol, and diol are demonstrated.
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