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
. 2022 Dec 5;61(49):e202212814.
doi: 10.1002/anie.202212814. Epub 2022 Nov 2.

Stereo- and Site-Selective Crotylation of Alcohol Proelectrophiles via Ruthenium-Catalyzed Hydrogen Auto-Transfer Mediated by Methylallene and Butadiene

Eliezer Ortiz  1 , Brian J Spinello  1 , Yoon Cho  1 , Jessica Wu  1 , Michael J Krische  1
Affiliations

Stereo- and Site-Selective Crotylation of Alcohol Proelectrophiles via Ruthenium-Catalyzed Hydrogen Auto-Transfer Mediated by Methylallene and Butadiene

Eliezer Ortiz et al. Angew Chem Int Ed Engl. .

Abstract

Iodide-bound ruthenium-JOSIPHOS complexes catalyze the redox-neutral C-C coupling of primary alcohols with methylallene (1,2-butadiene) or 1,3-butadiene to form products of anti-crotylation with good to excellent levels of diastereo- and enantioselectivity. Distinct from other methods, direct crotylation of primary alcohols in the presence of unprotected secondary alcohols is possible, enabling generation of spirastrellolide B (C9-C15) and leucascandrolide A (C9-C15) substructures in significantly fewer steps than previously possible.

Keywords: Alcohols; Crotylation; Dienes; Enantioselectivity; Ruthenium Catalysis.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Asymmetric carbonyl crotylation: A gateway to polyketide structural motifs.
Figure 2.
Figure 2.
Enantioselective ruthenium-catalyzed C-C coupling of alcohols.
Scheme 1.
Scheme 1.
Stereo- and site-selective methylallene-mediated carbonyl crotylation from the aldehyde oxidation level, gram-scale butadiene-mediated crotylations and late-stage functionalizations.a aYields of material isolated by silica gel chromatography. Enantioselectivities determined by HPLC analysis. Diastereoselectivities determined by 1H NMR analysis of crude reaction mixtures and refer to the major isomer vs all other isomers.
Scheme 2.
Scheme 2.
Generation of spirastrellolide B (C9-C15) and leucascandrolide A (C9-C15) substructures. aYields of material isolated by silica gel chromatography. Enantioselectivities determined by HPLC analysis. Diastereoselectivities determined by 1H NMR analysis of crude reaction mixtures and refer to the major isomer vs all other isomers. LLS = Longest linear sequence.
Scheme 3.
Scheme 3.
Proposed mechanism for enantioselective methylallene-mediated carbonyl crotylation via ruthenium-JOSIPHOS-catalyzed hydrogen auto-transfer of primary alcohols and deuterium labelling experiment.a aThe pattern of deuterium incorporation in deuterio-3a was assigned by 1H NMR, 2H NMR and HRMS. See Supporting Information for further details.
See this image and copyright information in PMC

References

    1. Rohr J, Angew. Chem. Int. Ed 2000, 39, 2847–2849; - PubMed
    2. Angew. Chem 2000, 112, 2967–2969;
    3. Weissman KJ, Leadlay F, Nat. Rev. Microbiol 2005, 3, 925–936; - PubMed
    4. Rimando AM, Baerson SR, eds., Polyketides: Biosynthesis, Biological Activity, and Genetic Engineering (ACS Symp. Ser.,Vol. 955), American Chemical Society, Washington DC, 2007.
    5. Li JW-H, Vederas JC, Science 2009, 325, 161–165. - PubMed
    1. Brown HC, Bhat KS, J. Am. Chem. Soc 1986, 108, 293–294; - PubMed
    2. Brown HC, Bhat KS, J. Am. Chem. Soc 1986, 108, 5919–5923. - PubMed
    1. For selected reviews on catalytic enantioselective carbonyl allylation and crotylation, see: Denmark SE, Fu J, Chem. Rev 2003, 103, 2763–2794; - PubMed
    2. Hall DG, Synlett 2007, 1644–1655;
    3. Yus M, González-Gómez JC, Foubelo F, Chem. Rev 2011, 111, 7774–7854; - PubMed
    4. Huo H-X, Duvall JR, Huang M-Y, Hong R, Org. Chem. Front 2014, 1, 303–320;
    5. Spielmann K, Niel G, de Figueiredo RM, Campagne J-M, Chem. Soc. Rev 2018, 47, 1159–1173. - PubMed
    1. For a recent review, see: Doerksen RS, Meyer CC, Krische MJ, Angew. Chem. Int. Ed 2019, 58, 14055–14064; - PMC - PubMed
    2. Angew. Chem 2019, 131, 14193–14202.
    1. Carey JS, Laffan D, Thomson C, Williams MT, Org. Biomol. Chem 2006, 4, 2337–2347. - PubMed

Publication types