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. 2025 Feb 21;27(7):1673-1678.
doi: 10.1021/acs.orglett.5c00054. Epub 2025 Feb 10.

Stereoselective Synthesis of Highly Functionalized Bicyclo[2.1.0]pentanes by Sequential [2 + 1] and [2 + 2] Cycloadditions

Brockton Keen  1 , Christina Cong  2 , Alberto Castanedo  2 , Geraint H M Davies  3 , Robert R Knowles  2 , Huw M L Davies  1
Affiliations

Stereoselective Synthesis of Highly Functionalized Bicyclo[2.1.0]pentanes by Sequential [2 + 1] and [2 + 2] Cycloadditions

Brockton Keen et al. Org Lett. .

Abstract

This study describes a method for the stereoselective synthesis of highly functionalized bicyclo[2.1.0]pentanes (housanes). The approach utilizes a two-step sequence, a silver- or gold-catalyzed cyclopropenation of alkynes followed by an intermolecular [2 + 2] photocycloaddition reaction with electron-deficient alkenes. The cyclopropenation is an established reaction of aryldiazoacetates. A regioselective [2 + 2] cycloaddition of the cyclopropane was developed using blue LED irradiation, a commercially available photocatalyst as a triplet-sensitizer, and low reaction temperature (-40 °C). The [2 + 2] cycloaddition is highly diastereoselective, and when enantioenriched cyclopropenes are used, it proceeds with enantioretention.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Summary of Current and Prior Work
Figure 1
Figure 1
Diastereoselectivity of the [2 + 2] cycloaddition.
Scheme 2
Scheme 2. Enantioselective Cyclopropenation
Scheme 3
Scheme 3. Telescoped [2 + 1]/[2 + 2] Cycloadditions
Scheme 4
Scheme 4. Proposed Mechanism for the [2 + 2] Cycloaddition
See this image and copyright information in PMC

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