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. 2018 Jun 25;9(30):6361-6367.
doi: 10.1039/c8sc02290a. eCollection 2018 Aug 14.

Enantioselective aza-Friedel-Crafts reaction of furan with α-ketimino esters induced by a conjugated double hydrogen bond network of chiral bis(phosphoric acid) catalysts

Manabu Hatano  1 , Haruka Okamoto  1 , Taro Kawakami  1 , Kohei Toh  1 , Hidefumi Nakatsuji  1 , Akira Sakakura  2 , Kazuaki Ishihara  1
Affiliations

Enantioselective aza-Friedel-Crafts reaction of furan with α-ketimino esters induced by a conjugated double hydrogen bond network of chiral bis(phosphoric acid) catalysts

Manabu Hatano et al. Chem Sci. .

Abstract

Chiral C 2- and C 1-symmetric BINOL-derived bis(phosphoric acid) catalysts, which have OP([double bond, length as m-dash]O)(OH)2/OP([double bond, length as m-dash]O)(OH)(OR) moieties at the 2,2'-positions, were developed and used for the enantioselective aza-Friedel-Crafts reaction of 2-methoxyfuran with α-ketimino esters for the first time. The intramolecular conjugated double hydrogen bond network is a key to increasing the Brønsted acidity and preventing deactivation of the catalysts. Highly functionalized α-amino acid derivatives with a chiral quaternary carbon center could be transformed into versatile optically active N- and O-heterocycles and an α-aryl-substituted serine.

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Figures

Fig. 1
Fig. 1. Design of chiral BINOL-derived bis(phosphoric acid) catalysts.
Fig. 2
Fig. 2. X-ray analysis of (R)-5c·(pyridine)2. Hydrogen atoms are partially omitted for clarity.
Scheme 1
Scheme 1. Role of active H+-centers in chiral C2-symmetric catalysts (R)-5b.
Fig. 3
Fig. 3. Non-linear effects of (R)-5b and (R)-4a.
Scheme 2
Scheme 2. Substrate scope in the enantioselective aza-FC reaction of 2-methoxyfuran 2 with aryl α-ketimino esters 7. (a) The reaction was carried out with (R)-10c (5 mol%), 7 (0.20 mmol, 1 equiv.), and 2 (2 equiv.) in dichloromethane (0.1 M based on 7) at –60 °C for 3 h. (b) 2-Ethoxyfuran was used instead of 2.
Scheme 3
Scheme 3. Transformation of alkyne and furan moieties.
Scheme 4
Scheme 4. Transformation to optically active α-aryl-substituted serine 21.
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References

    1. For reviews on asymmetric hydrogen bond network.

    2. Pihko P. M. Angew. Chem., Int. Ed. 2004;43:2062. - PubMed
    3. Taylor M. S., Jacobsen E. N. Angew. Chem., Int. Ed. 2006;45:1520. - PubMed

    1. For reviews on chiral Brønsted acids.

    2. Akiyama T. Chem. Rev. 2007;107:5744. - PubMed
    3. Terada M. Synthesis. 2010;2010:1929.
    4. Kampen D., Reisinger C. M., List B. Top. Curr. Chem. 2010;291:395. - PubMed
    5. Parmar D., Sugiono E., Raja S., Rueping M. Chem. Rev. 2014;114:9047. - PubMed
    6. Akiyama T., Mori K. Chem. Rev. 2015;115:9277. - PubMed
    7. Parmar D., Sugiono E., Raja S., Rueping M. Chem. Rev. 2017;117:10608. - PubMed
    8. Merad J., Lalli C., Bernadat G., Maury J., Masson G. Chem.–Eur. J. 2018;24:3925. - PubMed
    1. Ishibashi H., Ishihara K., Yamamoto H. Chem. Rec. 2002;2:177. - PubMed
    2. Yamamoto H., Futatsugi K. Angew. Chem., Int. Ed. 2005;44:1924. - PubMed
    1. Huang Y., Unni A. K., Thadani A. N., Rawal V. H. Nature. 2003;424:146. - PubMed
    2. McDougal N. T., Schaus S. E. J. Am. Chem. Soc. 2003;125:12094. - PubMed
    3. Thadani A. N., Stankovic A. R., Rawal V. H. Proc. Natl. Acad. Sci. U. S. A. 2004;101:5846. - PMC - PubMed
    4. Unni A. K., Takenaka N., Yamamoto H., Rawal V. H. J. Am. Chem. Soc. 2005;127:1336. - PubMed
    1. Momiyama N., Yamamoto H. J. Am. Chem. Soc. 2005;127:1080. - PMC - PubMed