2-(Trialkylsilyl)aryl trifluoromethanesulfonates as aryne precursors in the develo...
| Grant number: | 11/11613-8 |
| Support type: | Regular Research Grants |
| Duration: | March 01, 2012 - April 30, 2014 |
| Field of knowledge: | Physical Sciences and Mathematics - Chemistry |
| Principal Investigator: | Alcindo Aparecido dos Santos |
| Grantee: | Alcindo Aparecido dos Santos |
| Home Institution: | Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
Abstract
This project aims the development and application of tri-component coupling reactionof amines, aldehydes and alkynes (A3) on the synthesis of hidroxy-propargylamines, which will be employed in the synthesis of alkaloids and other nitrogen containingbioactive compounds. A3-coupling reaction is a power tool for the carbon-carbon andcarbon-heteroatom bond formation allowing the preparation of functionalized skeletons of great synthetic utility. The proposal is centered in the coupling of anorganometallic generated in situ from a terminal alkynol and a metal salt or complex, and a nitrogen containing electrophile (imine or iminium salt). In previous investigations we prepared some hydroxy-propargylpiperidones by the A3-couplingreaction of aldehydes, 4-piperidone and alkynols. These compounds were submittedto an enzymatic kinetic resolution study. In this way, here we intend to investigate inthis project the preparation of palladacycle derivatives to evaluate its catalyticactivities; the piperidonic A3-coupling products will be converted into propargylamine derivatives to evaluate their biological activities. The conversion of propargylpiperidones (tertiary amines) in the corresponding primary amines, resulting inhydroxy-propargylamines precursors of cyclic bioactive alkaloids, including doublebond unsaturated ones, which could be prepared by chemoselective triple bondreduction. Procedures involving alternative NH2 source reagents instead of piperidonehydrate and also the asymmetric version of the A3-coupling reaction will beinvestigated. Particularly, we intend to use optically active benzylamines and 2-methyl-2-propanesulfinamide as well catalytic asymmetric ligands. (AU)