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. 2016 Feb 24;55(9):3077-80.
doi: 10.1002/anie.201510909. Epub 2016 Jan 28.

Reductive Chlorination and Bromination of Ketones via Trityl Hydrazones

Julius R Reyes  1 , Viresh H Rawal  2
Affiliations

Reductive Chlorination and Bromination of Ketones via Trityl Hydrazones

Julius R Reyes et al. Angew Chem Int Ed Engl. .

Abstract

A method is presented for the direct transformation of a ketone to the corresponding reduced alkyl chloride or bromide. The process involves the reaction of a ketone trityl hydrazone with tBuOCl to give a diazene which readily collapses to the α-chlorocarbinyl radical, reduction of which by a hydrogen atom source gives the alkyl chloride product. The use of N-bromosuccinimide provides the corresponding alkyl bromide. This unique transformation provides a reductive halogenation that complements Barton's redox-neutral vinyl halide synthesis.

Keywords: diastereoselectivity; halogenation; hydrazones; radical reactions; synthetic methods.

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Figures

Figure 1
Figure 1
Welwitindolinone B and potential precursors.
Figure 2
Figure 2
Synthesis of organochlorides from hydrazone precursors.
Figure 3
Figure 3
Optimization of reaction parameters. [a] Reactions performed in THF; NMR yield.
See this image and copyright information in PMC

References

    1. Bhat V, Rawal VH. Chem Commun. 2011;47:9705–9707. - PubMed
    2. Bhat V, MacKay JA, Rawal VH. Tetrahedron. 2011;67:10097–10104. - PMC - PubMed

    1. Both Shea and Garg have noted similar challenges in converting an alcohol to the chloride. See: Cleary L, Pitzen J, Brailsford JA, Shea KJ. Org Lett. 2014;16:4460–4463.Weires NA, Styduhar ED, Baker EL, Garg NK. J Am Chem Soc. 2014;136:14710–14713.

    1. Gorthey LA, Vairamani M, Djerassi C. J Org Chem. 1985;50:4173–4182.
    2. Albone KS, Macmillan J, Pitt AR, Willis CL. Tetrahedron. 1986;42:3203–3214.
    3. Snyder DC. J Org Chem. 1995;60:2638–2639.
    4. Korakas P, Chaffee S, Shotwell JB, Duque P, Wood JL. Proc Natl Acad Sci USA. 2004;101:12054–12057. - PMC - PubMed
    5. Pluempanupat W, Chavasiri W. Tetrahedron Lett. 2006;47:6821–6823.

    1. Gribble GW. Acc Chem Res. 1998;31:141–152.Gribble GW. Heterocycles. 2012;84:157–207.Acutumine S, King M, Herzon SB. Alkaloids Chem Biol. 2014;73:161–222.Chlorosulpholipids: Bedke DK, Vanderwal CD. Nat Prod Rep. 2011;28:15–25.Rhodomelaceae: Wang B-G, Gloer JB, Ji N-Y, Zhao J-C. Chem Rev. 2013;113:3632–3685.

    1. Synthesis of alkyl chlorides from vinyl halides: Iwasaki K, Wan KK, Oppedisano A, Crossley SWM, Shenvi RA. J Am Chem Soc. 2014;136:1300–1303.King SM, Ma X, Herzon SB. J Am Chem Soc. 2014;136:6884–6887.Lo JC, Gui J, Yabe Y, Pan CM, Baran PS. Nature. 2014;516:343–348.

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