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. 2022 May 6;24(17):3217-3222.
doi: 10.1021/acs.orglett.2c01004. Epub 2022 Apr 21.

Diastereoselective Substitution Reactions of Acyclic β-Alkoxy Acetals via Electrostatically Stabilized Oxocarbenium Ion Intermediates

Amanda Ramdular  1 , K A Woerpel  1
Affiliations

Diastereoselective Substitution Reactions of Acyclic β-Alkoxy Acetals via Electrostatically Stabilized Oxocarbenium Ion Intermediates

Amanda Ramdular et al. Org Lett. .

Abstract

Substitution reactions of acyclic β-alkoxy acetals proceeded with generally high diastereoselectivities (>90:10) to form the anti product. Mechanistic experiments supplemented with computational studies suggest that, upon activation of the acetal, the resulting oxocarbenium ion is electrostatically stabilized by the β-alkoxy group. This stabilization defines the conformation of the reactive intermediate, which can be attacked preferentially from the more exposed face, leading to the observed products.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.. Conformations of the oxocarbenium ion derived from acetal 4.
Figure 2.
Figure 2.. Change in distance between C3 to O with aryloxy groups of varying electron-donating ability.
Scheme 1.
Scheme 1.. Influence of alkoxy group on diastereoselectivity.
Scheme 2.
Scheme 2.. Reactive pathways of the electrostatically stabilized oxocarbenium ion intermediate 24.
aYield reported of impure compound.
See this image and copyright information in PMC

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