From one to two quaternary centers: Ester or nitrile α-alkylation applied to bioactive alkaloids. Issue 52 (27th December 2018)

• Record Type: Journal Article
• Authors: Voute, Nicholas; Neal, Andrew R.; Medda, Federico; Johnston, Craig A.; Slawin, Alexandra M.Z.; Westwood, Nicholas J.
• Is Part Of: Tetrahedron. Volume 74:Issue 52(2018)
• Page Start: 7399
• Page End: 7407
• Publication Date: 2018-12-27
• Subjects: Dehaloperophoramidine -- Diastereoselective -- Quaternary -- Stereocenter; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2018.10.077
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The synthesis of all-carbon quaternary centers remains a challenge. Here we describe studies on the formation of two adjacent all-carbon quaternary centers in the context of the planned synthesis of the bioactive natural products perophoramidine and the communesins. In one approach the key step involves ester-alkylation using either allyl bromide or formaldehyde as the electrophile. An unexpected rapid auto-oxidation reaction during the synthesis of the alkylation substrates limited the scalability of this approach. In a second route, alkylation of a nitrile-containing precursor was planned. The use of the TosMIC reagent on a complex substrate gave the nitrile for alkylation. The assignment of the relative stereochemistry of the products was done through the extensive use of small molecule X-ray crystallography. Graphical abstract: