Access to trans‐3,4‐Dihydroxy‐2‐alkylpyrrolidines and Piperidines by Use of Stereodefined Cyclic N,O‐Acetals as a Diversity‐Generating Element

Abstract

A highly efficient and stereoselective synthetic pathway towards trans-3,4-dihydroxy-2-alkylpyrrolidines and piperidines is described. The nature of the protecting groups on the hydroxyl moieties played a crucial role on the trans selectivity. By using this method, a concise total synthesis of (-)-2-epilentiginosine has been achieved.

A concise synthetic method towards (−)-swainsonine and its 8-epimer by using palladium-catalyzed asymmetric hydroamination of alkoxyallene as the key strategy

“…In our previous study, the nature of the protective group proved to be of critical importance in achieving high cis-selectivity in the Lewis acid-mediated CeC bond formation from the N,O-acetal intermediate D. 11c, 13 We decided to use the bisbenzyl ether (OP¼OCH 2 Ph) because the benzyl moiety can be easily removed under the hydrogenation condition for the formation of the lactone 3a (and 3b) from B.…”

Synthesis of Stereocontrolled Degradable Polymer by Living Cascade Enyne Metathesis Polymerization

“…Rhee et al. reported the Pd‐catalyzed asymmetric hydroamination of alkoxyallenes to produce highly enantioselective N , O ‐acetals from readily available amines (Figure 1B) [40–42] and proposed a reaction mechanism for the allylic substitution of the Pd–π–allyl complex intermediate [43] . Under mild reaction conditions, highly chemoselective 3,4‐dihydroxy‐2‐alkylpyrrolidines and piperidines were enantioselectively prepared using diversity‐generating elements [44,45] …”

“…[39] Acetal structures are versatile functional groups for protecting carbonyl groups in organic synthesis, bioactive components in pharmaceuticals, and application to hydrolyzable backbone structures in degradable polymers and drug delivery systems. Rhee et al reported the Pd-catalyzed asymmetric hydroamination of alkoxyallenes to produce highly enantioselective N,O-acetals from readily available amines (Figure 1B) [40][41][42] and proposed a reaction mechanism for the allylic substitution of the Pd-π-allyl complex intermediate. [43] Under mild reaction conditions, highly chemoselective 3,4-dihydroxy-2-alkylpyrrolidines and piperidines were enantioselectively prepared using diversitygenerating elements.…”

β-Oxidation of Ynamides into N,O-Acetals by mCPBA: Application in Enantioselective Intermolecular Transacetalization

“…Given the scarcity of β-oxidations of ynamides, we disclose herein a selective oxidation of ynamides by a common benchtop oxidant, m CPBA, into β-oxo-α- N,O -acetals in the absence of any catalyst. The N,O -acetals are common in bioactive natural products and medicinal agents, and they are also used as a diastereo-controlling element in organic synthesis . However, enantioselective synthesis of this moiety, particularly in a less stable acyclic platform, has been very challenging. , We present herein a novel intermolecular transacetalization strategy where configurationally labile O- acyl- N , O- acetals are converted into configurationally stable O- alkyl- N , O- acetals in a highly enantioselective fashion.…”