Cyclobutanes derived from the dimerization of cinnamic acids are the core scaffolds of many molecules with potentially interesting biological activities. By utilizing a powerful flow photochemistry platform developed in our laboratory, we have evaluated the effects of flow on the dimerization of a range of cinnamate substrates. During the course of the study we also identified a bis(thiourea) catalyst that facilitates better reactivity and moderate diastereoselectivity in the reaction. Overall, we show that carrying out the reaction in flow in the presence of the catalyst affords consistent formation of predictable cyclobutane diastereomers.
Even though there are dozens of biologically active 2‐substituted and 2,6‐disubstituted piperidines, only a limited number of approaches exist for their synthesis. Herein is described two Mannich‐type additions to nitrones, one using β‐ketoacids under catalyst‐free conditions and another using methyl ketones in the presence of chiral thioureas, which can generate a broad array of such 2‐substituted materials, as well as other ring variants, in the form of β‐N‐hydroxy‐aminoketones. Both processes have broad scope, with the latter providing products with high enantioselectivity (up to 98 %). The combination of these methods, along with other critical steps, has enabled 8‐step total syntheses of the 2,6‐disubstituted piperidine alkaloids (−)‐lobeline and (−)‐sedinone.
Despite the array of advances that have been made in Pictet–Spengler chemistry, particularly as it relates to the synthesis of β-carboline derivatives of both natural and designed origin, the ability...
Cyclobutanes derived from the dimerization of cinnamic acids are the core scaffolds of many molecules with potentially interesting biological activities.Byutilizing apowerful flow photochemistry platform developed in our laboratory, we have evaluated the effects of flowo nt he dimerization of arange of cinnamate substrates.During the course of the study we also identified abis(thiourea) catalyst that facilitates better reactivity and moderate diastereoselectivity in the reaction. Overall, we showt hat carrying out the reaction in flow in the presence of the catalyst affords consistent formation of predictable cyclobutane diastereomers.
Even though there are dozens of biologically active 2-substituted and 2,6-disubstituted piperidines,o nly al imited number of approaches exist for their synthesis.H erein is described two Mannich-type additions to nitrones,one using bketoacids under catalyst-free conditions and another using methyl ketones in the presence of chiral thioureas,w hichc an generate abroad arrayofs uch 2-substituted materials,a swell as other ring variants,i nt he form of b-N-hydroxy-aminoketones.B oth processes have broad scope,w ith the latter providing products with high enantioselectivity (up to 98 %). The combination of these methods,a long with other critical steps,has enabled 8-step total syntheses of the 2,6-disubstituted piperidine alkaloids (À)-lobeline and (À)-sedinone. Scheme 1. Selected piperidine-containing natural products, precedent for enantioselective functionalizations to generate such heterocycles, and two unique approaches based on using nitrones.
2 + 2] Photocycloaddition of Cinnamates in Flow and Development of a Thiourea Catalyst. -The bis(thiourea)-catalyzed dimerization of cinnamates (I) in a flow photoreactor gives rise to diaryl-cyclobutanedicarboxylates as a mixture of diastereomers (II) and (III). -(TELMESANI, R.; PARK, S. H.; LYNCH-COLAMETA, T.; BEELER*, A. B.; Angew.
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