Highly diastereoselective synthesis of N-substituted 4-(diethoxyphosphoryl)-pyrrolidines-3-carboxylate starting from tetraethyl methylenediphosphonate

Abstract

 This paper describes a convenient synthesis of novel series of 3,4-disubstituted pyrrolidines based on the aza-Michael addition of primary amines to 3,4-difunctionalized-1,3-diene followed by an intramolecular cyclization.

Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004–2024

“…Amri et al reported the use of this compound in the preparation of the diene 170 through a sequence that involves an alkylation with methyl bromoacetate and a Wittig–Horner reaction using formaldehyde (Scheme ). The diene 170 was subsequently used in the condensation with primary amines 171 to obtain a mixture of cis / trans 3,4-disubstituted pyrrolidines 172 in moderate to good yields, with the trans diastereoisomer being the major product …”

“…The diene 170 was subsequently used in the condensation with primary amines 171 to obtain a mixture of cis/trans 3,4disubstituted pyrrolidines 172 in moderate to good yields, with the trans diastereoisomer being the major product. 142 To prepare 2,5-disubstituted pyrrolidines 174, Stahl ́s research group developed a Pd(II)-catalyzed oxidative cyclization of alkenes bearing tert-butanesulfinamide nucleophiles (173). 143 Even though they only reported one example using a phosphonylated alkene, it is important to note that only a single diastereomer was detected because of the presence of the sulfinyl group and the α-phosphonate near the nitrogen atom (Scheme 33).…”

Highly stereoselective synthesis of functionalized 1,3-dienes from a new allyl bromide

“…Previously, we have reported a new synthetic route to the diethyl (E)-1-(bromomethyl)-2-cyanovinylphosphonate 1 39 and its application in the synthesis of new vinylphosphonates 40,41 . Following our interest in the synthesis of polyfunctionalized 1,3-dienes [42][43][44] , we have sought to investigate, in the present work, the transformation of allyl bromide 1 into 1,3-dienes and the conditions of their preparation. For this purpose, we explored two ways which allow to obtain two families of 1,3-dienes 3 and 4 (Scheme 1), namely the use of allyl bromide 1 in an olefination type Wittig-Horner reaction (Route a) as well as its displacement using nitroalkane salts (route b).…”