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
. 2019 Aug 20;10(42):9679-9683.
doi: 10.1039/c9sc03531a. eCollection 2019 Nov 14.

Ligand-controlled diastereodivergent, enantio- and regioselective copper-catalyzed hydroxyalkylboration of 1,3-dienes with ketones

Jian-Jun Feng  1 , Yan Xu  1 , Martin Oestreich  1
Affiliations

Ligand-controlled diastereodivergent, enantio- and regioselective copper-catalyzed hydroxyalkylboration of 1,3-dienes with ketones

Jian-Jun Feng et al. Chem Sci. .

Abstract

A copper-catalyzed three-component coupling of 1,3-dienes, bis(pinacolato)diboron, and ketones allows for the chemo-, regio-, diastereo- and enantioselective assembly of densely functionalized tertiary homoallylic alcohols. The relative configuration of the vicinal stereocenters is controlled by the chiral ligand employed. Subsequent transformations illustrate the versatility of these valuable chiral building blocks.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1. Transition-metal-catalyzed intermolecular borylative coupling reactions of ketones for the construction of tertiary homoallylic alcohols. cod = cycloocta-1,5-diene, pin = pinacolato.
Scheme 2
Scheme 2. Scope I: variation the ketone.a–c aCondition A: CuOAc (10 mol%), L1 (12 mol%), NaOtBu (40 mol%), ketone 1 (0.20 mmol), isoprene (2a, 1.0 mmol), and B2(pin)2 (1.5 equiv.) in toluene (2 mL) at –30 °C. Condition B: CuOAc (5.0 mol%), L9 (6.0 mol%), NaOtBu (40 mol%), ketone 1 (0.40 mmol), isoprene (2a, 2.0 mmol), and B2(pin)2 (1.5 equiv.) in toluene/THF – 8 : 2 (3.5 mL) at –20 °C. bYields are combined isolated material; diastereomers are usually separable by flash chromatography on silica gel. cThe enantiomeric excess of the major diastereomer was determined by HPLC analysis on chiral stationary phases. dCuOAc (15 mol%) and L1 (18 mol%) were used. eCuOAc (10 mol%) and L9 (12 mol%) were used. fanti-4ja: 29% ee. ganti-4ja: 80% ee. hee value of anti-4la. isyn-4ma: 78% ee. jsyn-4na: 72% ee.
Scheme 3
Scheme 3. Scope II: variation of the 1,3-diene.a–c For footnotes a–c, see Scheme 2. dThe absolute configuration was assigned by chemical correlation after separation of the diastereomers by flash chromatography on silica gel (see the ESI†). eanti-4ab: 84% ee. fCuOAc (8.0 mol%) and L9 (10 mol%) were used. gRun at –5 °C with CuOAc (10 mol%), L9 (12 mol%), NaOtBu (50 mol%), and B2(pin)2 (2.0 equiv.). hCuOAc (15 mol%) and L1 (18 mol%) were used.
Scheme 4
Scheme 4. Tertiary homoallylic alcohols as versatile building blocks. (a) PhBr (1.8 equiv.), Pd(OAc)2 (5.0 mol%), RuPhos (10 mol%), KOtBu (3.0 equiv.), toluene/H2O (10/1), 80 °C, 24 h; (b) Pd/C (10%), H2 (1 atm), MeOH, rt, 26 h; (c) (i) MsCl (1.5 equiv.), Et3N (1.5 equiv.), CH2Cl2, 0 °C to rt, 50 min; (ii) NaN3 (2.0 equiv.), DMF/H2O (10/1), 80 °C, 12 h; (d) (i) NaH (2.0 equiv.), allyl bromide (1.1 equiv.), THF, 0 °C to rt, 14 h; (ii) Hoveyda–Grubbs II (5.0 mol%), CH2Cl2, Δ, 12 h; (e) (i) TsCl (2.4 equiv.), pyridine, 0 °C to rt, 24 h; (ii) nBuLi (1.1 equiv.), –25 °C to rt, 15 h. Ms = methanesulfonyl.
See this image and copyright information in PMC

References

    1. For reviews of related asymmetric allylation of carbonyl compounds, see:

    2. Liu Y.-L., Lin X.-T. Adv. Synth. Catal. 2019;361:876–918.
    3. Hatano M., Ishihara K. Synthesis. 2008:1647–1675.
    4. Denmark S. E., Fu J. Chem. Rev. 2003;103:2763–2793. - PubMed
    1. Yus M., González-Gómez J. C., Foubelo F. Chem. Rev. 2013;113:5595–5698. - PubMed

    1. With allylboron reagents:

    2. Wada R., Oisaki K., Kanai M., Shibasaki M. J. Am. Chem. Soc. 2004;126:8910–8911. - PubMed
    3. Lou S., Moquist P. N., Schaus S. E. J. Am. Chem. Soc. 2006;128:12660–12661. - PubMed
    4. Schneider U., Ueno M., Kobayashi S. J. Am. Chem. Soc. 2008;130:13824–13825. - PubMed
    5. Shi S.-L., Xu L.-W., Oisaki K., Kanai M., Shibasaki M. J. Am. Chem. Soc. 2010;132:6638–6639. - PubMed
    6. Barnett D. S., Moquist P. N., Schaus S. E. Angew. Chem., Int. Ed. 2009;48:8679–8682. - PMC - PubMed
    7. Alam R., Vollgraff T., Eriksson L., Szabó K. J. J. Am. Chem. Soc. 2015;137:11262–11265. - PubMed
    8. Robbins D. W., Lee K. A., Silverio D. L., Volkov A., Torker S., Hoveyda A. H. Angew. Chem., Int. Ed. 2016;55:9610–9614. - PMC - PubMed
    9. Lee K. A., Silverio D. L., Torker S., Robbins D. W., Haeffner F., van der Mei F. W., Hoveyda A. H. Nat. Chem. 2016;8:768–777. - PMC - PubMed
    10. van der Mei F. W., Qin C., Morrison R. J., Hoveyda A. H. J. Am. Chem. Soc. 2017;139:9053–9065. - PMC - PubMed

    1. With allylsilicon reagents:

    2. Yamasaki S., Fujii K., Wada R., Kanai M., Shibasaki M. J. Am. Chem. Soc. 2002;124:6536–6537. - PubMed
    3. Wadamoto M., Yamamoto H. J. Am. Chem. Soc. 2005;127:14556–14557. - PubMed
    4. Wadamoto M., Naodovic M., Yamamoto H. Eur. J. Org. Chem. 2009:5132–5134. - PMC - PubMed

    1. With allyltin reagents:

    2. Casolari S., D'Addario D., Tagliavini E. Org. Lett. 1999;1:1061–1063.
    3. Waltz K. M., Gavenonis J., Walsh P. J. Angew. Chem., Int. Ed. 2002;41:3697–3600. - PubMed
    4. Cunningham A., Woodward S. Synthesis. 2002:43–44.
    5. Kim J. G., Waltz K. M., Garcia I. F., Kwiatkowski D., Walsh P. J. J. Am. Chem. Soc. 2004;126:12580–12585. - PubMed
    6. Teo Y.-C., Goh J.-D., Loh T.-P. Org. Lett. 2005;7:2743–2745. - PubMed
    7. Kim J. G., Camp E. H., Walsh P. J. Org. Lett. 2006;8:4413–4416. - PMC - PubMed
    8. Zhang X., Chen D., Liu X., Feng X. J. Org. Chem. 2007;72:5227–5233. - PubMed