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 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-enoate was employed in an improved total synthesis of the anti-tumor antibiotic (-)-agelastatin A. A series of N-sulfinyl aza-Morita-Baylis-Hillman products were prepared by addition of vinylaluminum and N-methylmorpholine-N-oxide reagents to enantiopure N-(p-toluenesufinyl)- and N-(2-methypropanesulfinyl)-derived sulfinimines from the least hindered direction via a non-chelation control mechanism. Hydrogenation of the these acrylates with a rhodium(I) catalyst afforded anti-alpha-substituted-beta-amino esters with a anti/syn selectivity of better than 17:1. This new methodology is useful for the asymmetric synthesis of anti-alpha-alkyl-beta-amino esters, which are valuable chiral building blocks for the preparation of biologically active nitrogen-containing natural products.

A comprehensive overview of synthetic strategies for nonaromatic nitrogen heterocycles Nitrogen heterocycles are extremely widely distributed in nature, as well as in synthetic substances found in pharmaceuticals, agrochemicals, and materials chemistry. With new structures and medicines that include these structures emerging yearly, and a vast new journal literature to describe them, anyone who wants to be effective in R&D needs to easily access a synthesis of the latest research. This state-of-the-art survey explores recent developments in the most widely used reactions, as well as completely new ones. Highlights the major modern synthetic methods known to obtain nonaromatic nitrogen heterocycles, and their practical applications Topics include enantioselective synthesis and catalysis, photocatalysis, biocatalysis, microwave-assisted synthesis, reactions of oximes and nitrones, and ionic liquids Discusses how to synthesize rings of specific sizes Covers sustainable synthetic approaches for obtaining salts Whether you are using nonaromatic nitrogen compounds as an academic researcher, a synthetic chemist in industry, or an advanced student, this book is an essential, up-to-date resource to support your work.

Chemistry