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. 2018 Aug 28;9(1):3488.
doi: 10.1038/s41467-018-05951-6.

Intermolecular selective carboacylation of alkenes via nickel-catalyzed reductive radical relay

Xian Zhao  1 , Hai-Yong Tu  1 , Lei Guo  1 , Shengqing Zhu  1 , Feng-Ling Qing  1   2 , Lingling Chu  3
Affiliations

Intermolecular selective carboacylation of alkenes via nickel-catalyzed reductive radical relay

Xian Zhao et al. Nat Commun. .

Abstract

The development of catalytic carboacylation of simple olefins, which would enable the rapid construction of ketones with high levels of complexity and diversity, is very challenging. To date, the vast majority of alkene carboacylation reactions are typically restricted to single- and two-component methodologies. Here we describe a three-component carboacylation of alkenes via the merger of radical chemistry with nickel catalysis. This reaction manifold utilizes a radical relay strategy involving radical addition to an alkene followed by alkyl radical capture by an acyl-nickel complex to forge two vicinal C-C bonds under mild conditions. Excellent chemoselectivity and regioselectivity have been achieved by utilizing a pendant weakly chelating group. This versatile protocol allows for facile access to a wide range of important β-fluoroalkyl ketones from simple starting materials.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Design of an intermolecular, selective carboacylation of alkenes. a Three-component carboacylation of olefins via nickel-catalyzed reductive radical relay. b Selectivity guided by a chelating group
Fig. 2
Fig. 2
Substrate scope. a Scope of alkenes. b Scope of acyl chlorides. c Scope of fluoroalkyl iodides. Reaction conditions: NiCl2•glyme (10 mol%), dtbbpy (20 mol%), alkene (1.0 equiv.), RfI (1.0 equiv.), acyl chloride (1.5 equiv.), Mn (3.0 equiv.), CH3CN [0.1 M], 25 oC, 20 h, see Supplementary Methods. All cited yields are isolated yields. Ar = 4-tert-butylphenyl, R = C6H13CO2. a Performed with 20 mol% NiCl2•glyme. b Reaction concentration is 0.05M CH3CN. cPerformed in CH3CN/DME (4:1) [0.1 M]
Fig. 3
Fig. 3
Chemoselectivity guided by pendant chelating groups. a Reactivity tuned by the chelating group. b Chemoselectivity in the presence of multiple double bonds. Reaction conditions: NiCl2•glyme (10 mol%), dtbbpy (20 mol%), alkene (1.0 equiv.), C4F9I (1.0 equiv.), acyl chloride (1.5 equiv.), Mn (3.0 equiv.), CH3CN [0.1 M], 25 oC, 20 h, see Supplementary Methods. All cited yields are isolated yields. Ar = 4-tert-butylphenyl. a36% of C4F9-alkene byproduct isolated. bAlkene consumed. cAlkene remained. dPerformed with 2 equiv. of alkene. e140% of alkene recovered. fPerformed in 4:1 CH3CN/DME [0.05 M]. g41% of alkene recovered. h17% of alkene recovered. i48 h
Fig. 4
Fig. 4
Derivations of compound 3. See Supplementary Methods. Ar = 4-tert-butylphenyl. PMB = 4-methoxybenzyl
Fig. 5
Fig. 5
Mechanistic studies. a Proposed mechanism. b Radical inhibition experiment. c Radical clock experiment. d Stoichiometric reaction of isolated Ni(II) complex. See Supplementary Discussion. Ar = 4-tert-butylphenyl. alkene = allyl heptanoate
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References

    1. Walter MW. Structure-based design of agrochemicals. Nat. Prod. Rep. 2002;19:278–291. doi: 10.1039/b100919m. - DOI - PubMed
    1. McDaniel R, et al. Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel “unnatural” natural products. Proc. Natl Acad. Sci. USA. 1999;96:1846–1851. doi: 10.1073/pnas.96.5.1846. - DOI - PMC - PubMed
    1. Moragas T, Correa A, Martin R. Metal-catalyzed reductive coupling reactions of organic halides with carbonyl-type compounds. Chem. Eur. J. 2014;20:8242–8258. doi: 10.1002/chem.201402509. - DOI - PubMed
    1. Willis MC. Transition metal catalyzed alkene and alkyne hydroacylation. Chem. Rev. 2010;110:725–748. doi: 10.1021/cr900096x. - DOI - PubMed
    1. Gooßen LJ, Rodríguez N, Gooßen K. Carboxylic acids as substrates in homogeneous catalysis. Angew. Chem. Int. Ed. 2008;47:3100–3120. doi: 10.1002/anie.200704782. - DOI - PubMed

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