Stereoselective Synthesis of Stannylated Dehydropiperidines and Dehydroazepanes

Abstract

An efficient allylation and butenylation of N‐alkoxycarbonyl‐2‐tributylstannyl‐1,3‐oxazolidines derived from (S)‐vinylglycinol or (S)‐styrylglycinol is described. After conversion of the stannylated azadienes into stannylated dienyl oxazolidinones, a ring‐closing metathesis generates dehydropiperidine or dehydroazepane; both are interesting scaffolds for the synthesis of polyfunctionnalized piperidines or azepanes. Whereas the dehydropiperidine synthesis was found to be selective regardless of the Grubbs catalyst used, we found that Grubbs II catalyst induced partial double bond isomerization in the dehydroazepane series. In addition, when allyltrimethylsilane was used in the ring‐opening reactions of N‐alkoxycarbonyl‐2‐tributylstannyl‐1,3‐oxazolidines, cyclopropyl derivatives were selectively obtained.

Sn−Li Transmetalation of α‐Aminoorganostannanes for the Stereoselective Synthesis of Substituted Dehydropiperidines and Dehydroazepanes

“…Such an isomerization has been previously observed and explained by a reversible addition of a ruthenium hydride complex on the double bond. [4,15] Scheme 2. Ring-closing metathesis of (S,S)-11b using Grubbs 1 or Grubbs 2 catalysts.…”

“…Organotin precursor 1 was obtained by a transacetalisation reaction [11a,19] between diethoxymethyltributyltin and (S)-vinylglycinol protected as N-CO 2 Me. [20] Details of the procedure have been previously reported [4] together with the identification of cis and trans isomers which was established on the basis of their NMR data. [21] Compound 2 was obtained by ring opening of 1 by soft alkenylmetals in the presence of Lewis acids and converted into oxazolidinone 3 before being submitted to ring-closing metathesis to afford 4.…”

“…Compounds 2-4 have been already prepared and fully characterized. [4] General procedure for Sn-Li transmetalation and electrophilic trapping of 3 or 4.…”

“…[3] In this context, the stereocontrolled synthesis of 2,6-disubstituted dehydropiperidines, which can be used as precursors of 2,6-disubstituted piperidines, presents a strong interest. Having in hand a series of 2-stannylated dehydropiperidines precursors, [4] we have evaluated their interest for the stereoselective synthesis of 2,6-disubstituted-3,4-dehydropiperidines through a sequence involving a Sn-Li transmetalation and an electrophilic trapping. We also considered this strategy for the synthesis of dehydroazepanes, since polyhydroxylated azepanes are also present in biological active products and have received some attention.…”

“…[11] These latter can be subsequently converted into the corresponding oxazolidinones 3 leading to the stannylated dehydropiperidines (or dehydroazepanes) 4 by ring closing metathesis. [4] Following a preliminary communication, the aim of the present work is to study the Sn-Li transmetalation reaction carried out on the stannylated oxazolidinones 3 and 4 by n-butyllithium in order to evaluate its diastereoselectivity and to rationalize the obtained results (Scheme 1). [12] We first examined the transmetalation reaction of stannylated oxazolidinones 4 before considering those of 3.…”