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. 2022 Jul 29;24(29):5468-5473.
doi: 10.1021/acs.orglett.2c02204. Epub 2022 Jul 20.

Sulfoxonium Ylides in Aminocatalysis: An Enantioselective Entry to Cyclopropane-Fused Chromanol Structures

Giorgiana Denisa Bisag  1 , Pietro Pecchini  1 , Michele Mancinelli  1 , Mariafrancesca Fochi  1 , Luca Bernardi  1
Affiliations

Sulfoxonium Ylides in Aminocatalysis: An Enantioselective Entry to Cyclopropane-Fused Chromanol Structures

Giorgiana Denisa Bisag et al. Org Lett. .

Abstract

The 1,1a,2,7b-tetrahydrocyclopropa[c]chromene, arising from fusion of chromane and cyclopropane rings is the core of medicinally relevant compounds. Engaging sulfoxonium ylides in enantioselective aminocatalytic reactions for the first time, a convenient entry to this scaffold is presented. Several ring-fused derivatives were obtained in moderate-to-good yields and enantioselectivities and with perfect diastereoselectivity at the cyclopropane, using an α,α-diphenylprolinol aminocatalyst. The versatility of the hemiacetal moiety in the products was leveraged to effect various synthetic manipulations.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. (a) Natural and Medicinally Relevant Compounds Embedding the 1,1a,2,7b-TH-Cyclopropa[c]chromene Framework; (b) This Work: enantioselective Access to This Scaffold via Aminocatalytic Cyclopropanation of Enals 1 with Sulfoxonium Ylides 2
Scheme 2
Scheme 2. Sulfoxonium Ylide 2 Substrate Scope
Conditions: 1a (0.1 mmol), 2 (0.15 mmol), catalyst (0.02 mmol), AcONa (0.02 mmol), CDCl3 (1 mL), rt, 12 h. Isolated yield after column chromatography. Determined by CSP (chiral stationary phase) HPLC analysis after column chromatography.
Scheme 3
Scheme 3. 2′-Hydroxycinnamaldehyde 1 Substrate Scope
Conditions: 1b–g (0.1 mmol), 2a (0.15 mmol), catalyst (0.02 mmol), AcONa (0.02 mmol), CDCl3 (1 mL), rt, 12 h. Isolated yield after column chromatography. Determined by CSP (chiral stationary phase) HPLC analysis after column chromatography. 1 equiv of NaOAc was used.
Scheme 4
Scheme 4. Synthetic Elaborations
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