Diastereoselective Access to Nonracemic 2-cis-Substituted and 2,6-cis-Disubstituted Piperidines

Abstract

Access to nonracemic amino ketones via a hydrozirconation/transmetalation/acylation sequence applied to Boc-protected 1-aminobut-3-enes is presented. This method was applied to the stereoselective synthesis of cyclic imines (or iminiums) which were diastereoselectively converted into 2-cis-substituted and 2,6-cis-disubstituted piperidines. The potential of this approach in the field of alkaloid synthesis was illustrated by the synthesis of (-)-coniine and (-)-indolizidine 209D. Furthermore, access to indolizidines bearing a quaternary center could also be envisioned through this strategy.

One-shot access to α,β-difunctionalized azepenes and dehydropiperidines by reductive cross-coupling of α-selenonyl-β-selenyl enamides with organic bromides

“…The improved efficiency of lithiation of the enecarbamate substrates (relative to the eneformamides) is probably a reflection of the robustness and/or superior directing ability of the Boc-group in such directed lithiations. 68 Congruous with our previous disclosure on the inertness of aryl chlorides under these reaction conditions, 55 we find that o-chlorobenzyl bromide selectively affords the benzylated product over the arylated product (see 4h). Instructively, while conditions for lithiation/trapping with carbon electrophiles are currently being fine-tuned, central among our objectives in the current study was the goal of preparing substrates bearing two pendant leaving groups, in view of utilizing them in one-pot vicinal carbo-functionalization protocols.…”

Synthesis of the spiroketal core of integramycin

“…Initially, the conditions recently reported by Vasse [12] were investigated (Scheme 3). In the event, treatment of the carboxylic acid 16 with Ghosez reagent [13] provided the corresponding acid chloride 7 , which was allowed to react with the hydrozirconation products of alkenes 6 and 10 in dichloromethane in the presence of a stoichiometric amount of CuBr·Me 2 S. The reaction was rather capricious and produced only modest amounts of the target compound.…”

Transmetalation of Alkylzirconocenes in Copper‐Catalyzed Alkyl–Alkynyl Cross‐Coupling Reactions

“…Since the first report of a Zr–Cu transmetalation reaction by Schwartz in 1977, only few innovations have been published to address the utility of alkylzirconium reagents under copper catalysis . These examples include asymmetric allylic alkylation,, conjugate addition with enones,, acylation using acid chlorides, bisalkynylation of zirconacycles with bromoalkynes and carbometalation of non‐activated alkynes by zirconacyclopentanes . Recently, Giri and co‐workers reported first Cu‐catalyzed cross‐coupling of arylzirconocenes with aryl and heteroaryl iodides .…”