Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May 10;145(18):10001-10006.
doi: 10.1021/jacs.3c02852. Epub 2023 Apr 26.

Three-Component Approach to Densely Functionalized Trifluoromethyl Allenols by Asymmetric Organocatalysis

Marie Deliaval  1 , Ramasamy Jayarajan  1 , Lars Eriksson  2 , Kálmán J Szabó  1
Affiliations

Three-Component Approach to Densely Functionalized Trifluoromethyl Allenols by Asymmetric Organocatalysis

Marie Deliaval et al. J Am Chem Soc. .

Abstract

We have developed a new three-component catalytic coupling reaction of alkynyl boronates, diazomethanes, and aliphatic/aromatic ketones in the presence of BINOL derivatives. The reaction proceeds with a remarkably high enantio- and diastereoselectivity (up to three contiguous stereocenters) affording tertiary CF3-allenols in a single operational step. The reaction proceeds under mild, neutral, metal-free conditions, which leads to a high level of functional group tolerance.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(a) Example of bioactive allenols. (b–f) Asymmetric synthesis of chiral allenols and CF3-allenes.
Figure 2
Figure 2
Synthetic scope of the three-component coupling. For standard reaction conditions see footnote a in Table 1. Unless otherwise stated a single diastereomer was obtained and the isolated yields are given. a1 mmol scale; The yield in parentheses is 19F NMR yield. bThe diastereoselectivity is 97:3 (5b, 5m), 91:9 (5p), and 96:4 (5q). c20 mol % catalyst 4 was used. dAt 40 °C. eAt room temperature.
Figure 3
Figure 3
(a) Extension to TMS-diazo methane. (b, c) Control reactions. (d) Reactions with aldehydes in two operational steps.
Figure 4
Figure 4
Suggested mechanism of the three-component reaction.
See this image and copyright information in PMC

References

    1. Hoffmann-Röder A.; Krause N. Synthesis and Properties of Allenic Natural Products and Pharmaceuticals. Angew. Chem., Int. Ed. 2004, 43, 1196–1216. 10.1002/anie.200300628. - DOI - PubMed
    1. Modern Allene Chemistry; Krause N.; Hashmi A. S. K., Eds.; Wiley-VCH: Weinheim, Germany, 2008.
    1. Huang X.; Ma S. Allenation of Terminal Alkynes with Aldehydes and Ketones. Acc. Chem. Res. 2019, 52, 1301–1312. 10.1021/acs.accounts.9b00023. - DOI - PubMed
    1. Chu W.-D.; Zhang Y.; Wang J. Recent advances in catalytic asymmetric synthesis of allenes. Catalysis Science & Technology 2017, 7, 4570–4579. 10.1039/C7CY01319A. - DOI
    1. Wang X.; Chen X.; Lin W.; Li P.; Li W. Recent Advances in Organocatalytic Enantioselective Synthesis of Axially Chiral Allenes. Adv. Synth. Catal. 2022, 364, 1212–1222. 10.1002/adsc.202200085. - DOI