What question did this study set out to answer?

Investigate a chiral-auxiliary-induced asymmetric synthesis method for generating 2-oxa-3-azabicyclo[3.1.1]heptanes.

March 26, 2026

Sc(OTf) 3 -Catalyzed Diastereoselective 3 + 3 Cycloaddition of Chiral Bicyclo1.1.0butanyl Imides and Nitrones

Key Points

Investigate a chiral-auxiliary-induced asymmetric synthesis method for generating 2-oxa-3-azabicyclo[3.1.1]heptanes.
Employed Sc(OTf)3 as a catalyst for the [3 + 3] cycloaddition of nitrones.
Utilized chiral bicyclo[1.1.0]butanes with (S)-4-benzyl-2-oxazolidinone to induce chirality.
Conducted DFT calculations to analyze reaction pathways and transition states.
Achieved yields of up to 98% in the cycloaddition reactions.
Observed moderate to excellent diastereoselectivities, with ratios exceeding 20:1 in some cases.
Calculated activation energy for the key transition state was 3.8 kcal/mol.

Abstract

A chiral-auxiliary-induced asymmetric synthesis of 2-oxa-3-azabicyclo3.1.1heptanes is described. This approach employs a new class of chiral bicyclo1.1.0butanes incorporating an (S)-4-benzyl-2-oxazolidinone auxiliary as the key chiral controller. The Sc(OTf)3-catalyzed 3 + 3 cycloaddition of nitrones proceeds smoothly in up to 98% yield with moderate to excellent diastereoselectivities (up to >20:1 dr) across 49 examples. The DFT calculation results are consistent with favorable nucleophilic attack on the Re face of the nitrone, leading to the generation of the S-configured chiral center. The calculated activation energy of the key transition state is 3.8 kcal/mol, in agreement with the excellent diastereoselectivity.

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Cite This Study

Sima et al. (Tue,) studied this question.

synapsesocial.com/papers/69c4cd05fdc3bde448918c71 https://doi.org/https://doi.org/10.1021/acs.orglett.6c00798

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