Title : Use of organocatalysis for the synthesis of phenyl-hydroxylated-butyric acids
Abstract:
Organocatalytic reactions are becoming powerful tools in the construction of complex molecular skeletons. In 2021, Benjamim List and David MacMillan were awarded the Nobel Prize in Chemistry for the development of asymmetric organocatalysis. In this work we used the organocatalysis reaction as key step to get the 4-(p-nitro)-phenylhydroxylated- butyric acids. The acids 1 (2,3-anti-3,4-syn) and 2 (2,3-syn-3,4-syn) were synthesized from TBSdihydroxyacetone (TBS-DHA) 3 and p-nitrobenzaldehyde 4 using an organocatalyzed aldol reaction as the key step. The stereoselectivity of the syn-aldol coupling was suggested as resulting from a transition state including a low energy anti-Z enamine, derived from the condensation of TBS-DHA and O-tBu-L-threonine. Selective anti- and syncarbonyl reduction of the carbonyl adducts led to 2,3-anti-3,4-syn and 2,3-syn-3,4-syn hydroxy compounds, respectively, which underwent the same sequence of transformations (ketal synthesis, primary TBS-deprotection, oxidation and deprotection) to afford 4-(p-nitro)-phenyl-hydroxylated-butyric acids 1 and 2 in seven steps and 22% and 24% overall yield, respectively.
Audience Takeaway Notes:
- The public will be able to learn the experimental part, which is one of the main challenges of this work;
- With this investigation in a similar way we will be able to prepare new chemical compounds;
- The methodology used allows its extension to the teaching component;
- Organocatalysis has numerous advantages.
