NEW METHODOLOGIES FOR THE ASYMMETRIC SYNTHESES OF AMINES AND NITROGEN HETEROCYCLES FROM ENANTIOPURE SULFINIMINES (N-SULFINYL IMINES) [article]

(:Unkn) Unknown, Rodrigo B. Andrade, Franklin A. Davis, University, My
2020
The objective of this research was to development new methodologies for the asymmetric syntheses of amine and natural products from enantiopure sulfinimines (N-sulfinyl imines). In this context, new methods was devised for the asymmetric synthesis of 2,5-cis and trans-disubstituted pyrrolidines from 3-oxo pyrrolidine 2-phosphonates, prepared by an intramolecular metal carbenoid N-H insertion from a sulfinimine derived delta-amino-alpha-diazo- beta-ketophosphonate. Horner-Wadsworth-Emmos
more » ... worth-Emmos reaction of the 3-oxo pyrrolidine 2-phosphonates and aldehydes provided pyrrolidine enones. Hydrogenation (Pd/H2) of the pyrrolidine enones gave cis-2,5-disubstituted pyrrolidines. Luche reduction the pyrrolidine enones followed by a TFA-NaBH3CN mediated hydroxy directed reduction provided the 2,5-trans products. (+)-Preussin, a potent antiviral and antitumor agent was prepared in 9 steps in 28% overall yield from the sulfinimine. An acid catalyzed intramolecular Mannich cyclization of a sulfinimine-derived N-sulfinyl syn-alpha-methyl-beta-amino ketones was employed for the asymmetric synthesis of 2,3,5,6-tetrasubstituted piperidinones. The beta-amino ketones were prepare by treatment of prochiral lithium Weinreb amide enolates with enantiopure (E)-N-(4-(benzyloxy)butylidene)-2,4,6-triisopropylbenzenesulfinamide. This new methodology was highlighted in the first asymmetric synthesis of the poison frog alkaloid (-)-indolizidine 221T. By manipulation of water concentration in tetrahydrofuran, syn- and anti-2,3-diamino esters were prepared by treatment of the lithium enolate of N-(diphenylmethylene) glycine ethyl ester with sulfinimines. Anhydrous THF afforded enantiopure syn-2,3-diamino esters with a syn/anti selectivity of better than 25:1. In a THF-H2O the anti-2,3-diamino esters were formed. The mechanism involves the generation of H2O-LDA species in the formation of enolate which inhibited the retro-Mannich fragmentation in the diamino ester species. (SR,2S,3R)-(-)-Ethyl-2-(N,N-dibenzylamino)-3-N-(p-toluenesulfinyl)amino-pent-4- [...]
doi:10.34944/dspace/2183 fatcat:yku3rijdczhblmaqe4mhc7t7ku