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 Oct 4;9(54):31654-31658.
doi: 10.1039/c9ra05532k. eCollection 2019 Oct 1.

Enantioselective bromination of axially chiral cyanoarenes in the presence of bifunctional organocatalysts

Yuuki Wada  1 , Akira Matsumoto  1 , Keisuke Asano  1 , Seijiro Matsubara  1
Affiliations

Enantioselective bromination of axially chiral cyanoarenes in the presence of bifunctional organocatalysts

Yuuki Wada et al. RSC Adv. .

Abstract

Enantioselective bromination of axially chiral cyanoarenes bearing high intrinsic rotational barriers via dynamic kinetic resolution using bifunctional organocatalysts is reported. Sequential addition of a brominating reagent in several portions at an optimized temperature was effective in accomplishing high enantioselectivities.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Enantioselective bromination of axially chiral cyanoarenes using bifunctional organocatalysts.
Fig. 1
Fig. 1. Brominating reagents.
Fig. 2
Fig. 2. Investigations of temperatures and procedures. Blue bar: reactions were run with 4a added in 1 portion. Red bar: reactions were run with 4a added in 5 portions. Green values represent yields of 2a isolated after silica gel column chromatography. At 0, −10, −20, and −30 °C, reactions were run for 24 h; at −40 °C, reactions were run for 72 h.
Fig. 3
Fig. 3. Relationships between ee and yield. Red line: reactions were run at −30 °C for 24 h with 4a added in 5 portions. Blue line: reactions were run at −40 °C for 72 h with 4a added in 5 portions. Red and blue values represent amounts of 4a used for each reaction.
Fig. 4
Fig. 4. Rotational barriers of substrate, intermediate, and product calculated at the M06-2X/6-311++G(2d,3p)//B3LYP/6-31+G(d,p) level of theory.
Scheme 2
Scheme 2. Reactions of substrates with substituted phenols. aReaction was run for 72 h.
Scheme 3
Scheme 3. Reactions with a substoichiometric amount of 4a.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Bringmann G. Menche D. Acc. Chem. Res. 2001;34:615. doi: 10.1021/ar000106z. - DOI - PubMed
    2. Kozlowski M. C. Morgan B. J. Linton E. C. Chem. Soc. Rev. 2009;38:3193. doi: 10.1039/B821092F. - DOI - PMC - PubMed
    3. Bringmann G. Gulder T. Gulder T. A. M. Breuning M. Chem. Rev. 2011;111:563. doi: 10.1021/cr100155e. - DOI - PubMed
    4. Zask A. Murphy J. Ellestad G. A. Chirality. 2013;25:265. doi: 10.1002/chir.22145. - DOI - PubMed
    5. Smyth J. E. Butler N. M. Keller P. A. Nat. Prod. Rep. 2015;32:1562. doi: 10.1039/C4NP00121D. - DOI - PubMed
    6. Covington C. L. Junior F. M. S. Silva J. H. S. Kuster R. M. de Amorim M. B. Polavarapu P. L. J. Nat. Prod. 2016;79:2530. doi: 10.1021/acs.jnatprod.6b00395. - DOI - PubMed
    1. McCarthy M. Guiry P. J. Tetrahedron. 2001;57:3809. doi: 10.1016/S0040-4020(01)00087-4. - DOI
    2. Chen Y. Yekta S. Yudin A. K. Chem. Rev. 2003;103:3155. doi: 10.1021/cr020025b. - DOI - PubMed
    3. Brunel J. M. Chem. Rev. 2005;105:857. doi: 10.1021/cr040079g. - DOI - PubMed
    4. Yoon T. P. Jacobsen E. N. Science. 2003;299:1691. doi: 10.1126/science.1083622. - DOI - PubMed
    1. Li Q. Green L. Venkataraman N. Shiyanovskaya I. Khan A. Urbas A. Doane J. W. J. Am. Chem. Soc. 2007;129:12908. doi: 10.1021/ja0747573. - DOI - PubMed
    2. Hayasaka H. Miyashita T. Nakayama M. Kuwada K. Akagi K. J. Am. Chem. Soc. 2012;134:3758. doi: 10.1021/ja2088053. - DOI - PubMed
    3. Wu Y.-L. Ferroni F. Pieraccini S. Schweizer W. B. Frank B. B. Spada G. P. Diederich F. Org. Biomol. Chem. 2012;10:8016. doi: 10.1039/C2OB25983D. - DOI - PubMed
    4. Pu L. Acc. Chem. Res. 2012;45:150. doi: 10.1021/ar200048d. - DOI - PubMed
    5. Wei G. Zhang S. Dai C. Quan Y. Cheng Y. Zhu C. Chem.–Eur. J. 2013;19:16066. doi: 10.1002/chem.201302726. - DOI - PubMed

    1. For selected recent reviews on enantioselective syntheses of axially chiral compounds, see ref. 1 and the following:

    2. Cozzi P. G. Emer E. Gualandi A. Angew. Chem., Int. Ed. 2011;50:3847. doi: 10.1002/anie.201008031. - DOI - PubMed
    3. Quinonero O. Bressy C. Bugaut X. Angew. Chem., Int. Ed. 2014;53:10861. doi: 10.1002/anie.201406263. - DOI - PubMed
    4. Wencel-Delord J. Panossian A. Leroux F. R. Colobert F. Chem. Soc. Rev. 2015;44:3418. doi: 10.1039/C5CS00012B. - DOI - PubMed
    5. Ma G. Sibi M. P. Chem.–Eur. J. 2015;21:11644. doi: 10.1002/chem.201500869. - DOI - PubMed
    6. Bencivenni G. Synlett. 2015;26:1915. doi: 10.1055/s-0034-1378712. - DOI
    7. Kumarasamy E. Raghunathan R. Sibi M. P. Sivaguru J. Chem. Rev. 2015;115:11239. doi: 10.1021/acs.chemrev.5b00136. - DOI - PubMed
    8. Shirakawa S. Liu S. Kaneko S. Chem.–Asian J. 2016;11:330. doi: 10.1002/asia.201500951. - DOI - PubMed
    9. Renzi P. Org. Biomol. Chem. 2017;15:4506. doi: 10.1039/C7OB00908A. - DOI - PubMed
    10. Zilate B. Castrogiovanni A. Sparr C. ACS Catal. 2018;8:2981. doi: 10.1021/acscatal.7b04337. - DOI
    11. Baudoin O. Eur. J. Org. Chem. 2005:4223. doi: 10.1002/ejoc.200500394. - DOI
    12. Bringmann G. Mortimer A. J. P. Keller P. A. Gresser M. J. Garner J. Breuning M. Angew. Chem., Int. Ed. 2005;44:5384. doi: 10.1002/anie.200462661. - DOI - PubMed
    13. Zhang D. Wang Q. Coord. Chem. Rev. 2015;286:1. doi: 10.1016/j.ccr.2014.11.011. - DOI
    14. Cherney A. H. Kadunce N. T. Reisman S. E. Chem. Rev. 2015;115:9587. doi: 10.1021/acs.chemrev.5b00162. - DOI - PMC - PubMed
    15. Loxq P. Manoury E. Poli R. Deydier E. Labande A. Coord. Chem. Rev. 2016;308:131. doi: 10.1016/j.ccr.2015.07.006. - DOI
    16. Tanaka K. Chem.–Asian J. 2009;4:508. doi: 10.1002/asia.200800378. - DOI - PubMed
    1. Gustafson J. L. Lim D. Miller S. J. Science. 2010;328:1251. doi: 10.1126/science.1188403. - DOI - PMC - PubMed
    2. Pathak T. P. Miller S. J. J. Am. Chem. Soc. 2012;134:6120. doi: 10.1021/ja301566t. - DOI - PMC - PubMed
    3. Barrett K. T. Miller S. J. J. Am. Chem. Soc. 2013;135:2963. doi: 10.1021/ja400082x. - DOI - PMC - PubMed
    4. Barrett K. T. Metrano A. J. Rablen P. R. Miller S. J. Nature. 2014;509:71. doi: 10.1038/nature13189. - DOI - PMC - PubMed
    5. Diener M. E. Metrano A. J. Kusano S. Miller S. J. J. Am. Chem. Soc. 2015;137:12369. doi: 10.1021/jacs.5b07726. - DOI - PMC - PubMed
    6. Miyaji R. Asano K. Matsubara S. J. Am. Chem. Soc. 2015;137:6766. doi: 10.1021/jacs.5b04151. - DOI - PubMed
    7. Miyaji R. Asano K. Matsubara S. Chem.–Eur. J. 2017;23:9996. doi: 10.1002/chem.201701707. - DOI - PubMed
    8. Miyaji R. Wada Y. Matsumoto A. Asano K. Matsubara S. Beilstein J. Org. Chem. 2017;13:1518. doi: 10.3762/bjoc.13.151. - DOI - PMC - PubMed