Asymmetric Syntheses of N-Boc 2-Substituted Pyrrolidines and Piperidines by Intramolecular Cyclization

Abstract

Asymmetric lithiation-substitutions by n-BuLi/(-)-sparteine with the N-Boc-N-(3-halopropyl)allylamines 1-4 provide the N-Boc-2-alkenylpyrrolidines (S)-5, (S)-6, and (S)-7 in yields of 31-93% with enantiomeric ratios (ers) from 65:35 to 90:10. These reactions are shown to involve an initial asymmetric deprotonation, but the enantiodetermining step is a subsequent asymmetric cyclization under the influence of the chiral ligand. Extension to formation of a piperidine is illustrated by reaction of N-Boc-(4-chlorobutyl)cinnamylamine (9) to afford (S)-N-Boc-2-(trans-βstyryl)piperidine ((S)-10) in 68% yield with an enantiomeric ratio (er) of 84:16. Analogous reactions with epoxide ring openings of N-Boc-N-(oxaalkenyl)benzylamines 11 and 12 afford the corresponding N-Boc-2-phenyl-3-(hydroxymethyl)pyrrolidine (13) in 67% yield with a diastereomeric ratio (dr) of 50:50 and ers of 97:3 and 95:5 and the corresponding N-Boc-2-phenyl-3-(hydroxymethyl)piperidine

Flavin‐Mediated Visible‐Light [2+2] Photocycloaddition of Nitrogen‐ and Sulfur‐Containing Dienes

“…To illustrate the overall facile synthetic approach to bicyclic compounds 12 – 15 , the synthesis of diene precursors 8 – 11 is depicted as a general retrosynthetic scheme in Scheme (for details, see the Supporting Information). The syntheses start from readily available allyl bromides and Boc‐protected cinnamylamine …”

Stereoselective Synthesis and Retentive Trapping of α‐Chiral Secondary Alkyllithiums Leading to Stereodefined α,β‐Dimethyl Carboxylic Esters

“…Alternatively, one can envision the use of a carboxylation of the chiral organolithium reagents of type 2 with ClCO 2 Et for preparing esters of type 1 stereoselectively (Scheme ). Although acyclic heteroatom‐stabilized chiral lithium reagents are well known, non‐stabilized secondary alkyllithiums have been less extensively studied . Recently, we reported that an I–Li‐exchange allows the generation of functionalized secondary alkyllithium reagents bearing remote functionalities (at position 3 or 4) .…”

Asymmetric Deprotonation with Alkyllithium–(−)‐Sparteine

“…The asymmetric lithiation/substitution of N-Boc-N-(3-chloropropyl)-2-alkenylamines 395 by n-BuLi/(−)-sparteine (11) provides (S)-N-Boc-2-(alken-1-yl)pyrrolidines 397 via the allyllithium-sparteine complexes 396 (equation 106) 182,288 . Similarly, the piperidine corresponding to 397 was obtained from the N-(4-chlorobutyl)amine.…”