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Diastereoselective [3 + 2] Cycloaddition between Tertiary Amine N-Oxides and Substituted Alkenes to Access 7-Azanorbornanes - PubMed

  • ️Mon Jan 01 2024

Diastereoselective [3 + 2] Cycloaddition between Tertiary Amine N-Oxides and Substituted Alkenes to Access 7-Azanorbornanes

Alexander H Cocolas et al. Org Lett. 2024.

Abstract

We have developed a diastereoselective synthesis of 43 novel 7-azanorbornanes using tertiary amine N-oxides and substituted alkenes. Our method uses an efficient [3 + 2] cycloaddition, starting from either commercially available or easily accessible precursors to generate yields up to 97% and diastereomeric ratios up to >20:1. Density functional theory (DFT) calculations were performed, suggesting that the observed diastereoselectivity is likely due to steric considerations.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. 7-Azanorbornane Relevance and Syntheses
Figure 1
Figure 1

(A) Minimized ground state for 10aa using M062x/jul-cc-pvTz. (B) X-ray structure of [10mb•H]BF4 (CD CCDC 2352512). Hydrogen atoms and BF4– anion omitted for clarity.

Scheme 2
Scheme 2. Substrate Scope

Expanded substrate scope found in SI, Scheme S1. (a) Reactions carried on a 0.4 mmol scale. Conditions: N-oxide (1.0 equiv) alkene (0.5 equiv), LDA (3.0 equiv), dry THF (0.1M), −78 °C to RT, N2. Isolated yields were reported. (b) Carried out on a 7.0 mmol scale. (c) LDA (4.5 equiv).

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