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. 2022 Jun 24;24(24):4371-4376.
doi: 10.1021/acs.orglett.2c01589. Epub 2022 Jun 10.

Catalytic Enantioselective Entry to Triflones Featuring a Quaternary Stereocenter

Francesca Franco  1 , Sara Meninno  1 , Jacob Overgaard  2 , Sergio Rossi  3 , Maurizio Benaglia  3 , Alessandra Lattanzi  1
Affiliations

Catalytic Enantioselective Entry to Triflones Featuring a Quaternary Stereocenter

Francesca Franco et al. Org Lett. .

Abstract

A highly enantioselective one-pot synthesis of functionalized triflones, bearing a quaternary stereocenter, has been developed, exploiting the Michael reaction of α-(trifluoromethylsulfonyl) aryl acetic acid esters with N-acryloyl-1H-pyrazole catalyzed by commercially available Takemoto's catalyst, followed by nucleophilic acyl substitution with alcohols. Preliminary investigations highlighted the attractive potential of the triflinate anion as the leaving group for stereocontrolled postfunctionalizations.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Approaches to Optically Enriched Triflones
Scheme 2
Scheme 2. Substrate Scope of the One-Pot Process,,
First step: 0.1 mmol scale of 1 (C 0.2 M) using 2f (1.5 equiv). Second step: addition of R2OH (50 equiv), in case of morpholine (3 equiv). Isolated yield after chromatography. Ee determined by chiral HPLC analysis.
Scheme 3
Scheme 3. One-Pot Derivatizations of Compounds 8 Involving Triflyl Group Displacement
Figure 1
Figure 1
Proposed model of stereoselection. Geometries and ΔΔG0 (kcal mol–1) of transition states related to the synthesis of enriched triflone 8a were calculated at the M062X/6-31G(d,p)/PCM (toluene) level of theory. Hydrogens are omitted for clarity.
Scheme 4
Scheme 4. Additional Derivatizations of Compounds 8
See this image and copyright information in PMC

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