Conclusions
In summary, a metal-free asymmetric hydrogenation of 6-substituted
phenanthridines was achieved by using chiral monoene derived borane
catalyst. a variety of dihydrophenanthridines were obtained in 81-96%
yields with up to 93% ee. The obvious difference between the two sides
of the N-ring was required to give reasonable reactivity and
enantioselectivity. However, the bulky substituents at the 6-position
would inhibit the reaction. Further efforts on searching for more
effective chiral catalyst and expanding their application in asymmetric
reactions are underway in our laboratory.
Experimental
Typical procedure for the asymmetric hydrogenation of
phenanthridine 1c : To a glass test tube (10 mL) in a nitrogen
atmosphere glovebox,
HB(C6F5)2 (2 )
(13.8 mg, 0.04 mmol), chiral alkene 5a (28.0 mg, 0.04 mmol),
and dry toluene (2.0 mL) were added. The resulting mixture was stirred
at room temperature for 5 min, followed by the addition of
phenanthridine 1c (122.2mg, 0.4 mmol). Then the tube was moved
to a stainless-steel autoclave, and the autoclave was purged three times
with H2 and the final pressure of H2 was
adjusted to 40 bar. The reaction was stirred at 40 °C for 16 h. The
solvent was removed under reduced pressure, and the crude residue was
purified by flash chromatography on silica with petroleum ether/ethyl
acetate (20/1) to afford dihydrophenanthridine 4c as a white
solid (112.2 mg, 91% yield, 80% ee).
Supporting Information
The supporting information for this article is available on the WWW
under https://doi.org/10.1002/cjoc.2023xxxxx.
Acknowledgement
We are grateful for the financial support from the National Natural
Science Foundation of China (21825108 and 22331011)
References
- (a) Stermitz, F. R.; Larson, K. A.; Kim, D. K. Structural Relations
among Cytotoxic and Antitumor Benzophenanthridine Alkaloid
Derivatives. J. Med. Chem. 1973 , 16 , 939–940.
(b) Chang, Y.-C.; Hsieh, P.-W.; Chang, F.-R.; Wu, R.-R.; Liaw, C.-C.;
Lee, K.-H.; Wu, Y.-C. Two New Protopines Argemexicaines A and B and
the Anti-HIV Alkaloid 6-Acetonyldihydrochelerythrine from Formosan
Argemone Mexicana. Planta Med . 2003 , 69 ,
148–152. (c) Fotie, J.; Bohle, D. S.; Olivier, M.; Gomez, M. A.;
Nzimiro, S. Trypanocidal and Antileishmanial Dihydrochelerythrine
Derivatives from Garcinia lucida. J. Nat. Prod . 2007 ,70 , 1650–1653. (d) Pegoraro, S.; Lang, M.; Dreker, T.; Kraus,
J.; Hamm, S.; Meere, C.; Feurle, J.; Tasler, S.; Prütting, S.; Kuras,
Z.; Visan, V.; Grissmer, S. Inhibitors of Potassium Channels
KV1.3 and IK-1 as Immunosuppressants. Bioorg.Med. Chem. Lett. 2009 , 19 , 2299–2304. (e)
Éles, J.; Beke, G.; Vágó, I.; Bozó, É.; Huszár, J.; Tarcsay, Á.;
Kolok, S.; Schmidt, É.; Vastag, M.; Hornok, K.; Farkas, S.; Domány,
G.; Keserű, G. M. Quinolinyl- and Phenantridinyl-acetamides as
Bradykinin B1 Receptor Antagonists. Bioorg. Med. Chem. Lett .2012 , 22 , 3095–3099.
- (a) Xiao, K.-J.; Chu, L.; Chen, G.; Yu, J.-Q. Kinetic Resolution of
Benzylamines via Palladium(II)-Catalyzed C–H Cross-Coupling. J.
Am. Chem. Soc . 2016 , 138 , 7796–7800. (b) Fandrick,
D. R.; Hart, C. A.; Okafor, I. S.; Mercadante, M. A.; Sanyal, S.;
Masters, J. T.; Sarvestani, M.; Fandrick, K. R.; Stockdill, J. L.;
Grinberg, N.; Gonnella, N.; Lee, H.; Senanayake, C. H.
Copper-Catalyzed Asymmetric Propargylation of Cyclic Aldimines.Org. Lett. 2016 , 18 , 6192–6195.
- (a) Ye, J.; Limouni, A.; Zaichuk, S.; Lautens, M. Synthesis of
Enantioenriched 5,6-Dihydrophenanthridine Derivatives through
retro-Carbopalladation of Chiral o -Bromobenzylamines.Angew. Chem., Int. Ed. 2015 , 54 , 3116–3120.
- (a)Yang, Z.; Chen, F.; Zhang, S.; He, Y.; Yang, N.; Fan, Q.-H.
Ruthenium-Catalyzed Enantioselective Hydrogenation of Phenanthridine
Derivatives. Org. Lett. 2017 , 19 , 1458–1461.
(b) Hu, S.-B.; Zhai, X.-Y.; Shen, H.-Q.; Zhou, Y.-G. Iridium-Catalyzed
Asymmetric Hydrogenation of Polycyclic
Pyrrolo/Indolo[1,2-a ]quinoxalines and Phenanthridines.Adv. Synth. Catal . 2018 , 360 , 1334–1339.
- Welch, G. C.; San Juan R. R.; Masuda, J. D.; Stephan, D. W.;
Reversible, Metal-Free Hydrogen Activation. Science ,2006 , 314 , 1124–1126.
- (a) Stephan, D. W.; Erker G. Frustrated Lewis Pairs: Metal-free
Hydrogen Activation and More. Angew. Chem., Int. Ed.2010 , 49 , 46–76. (b) Soόs, T. Design of Frustrated
Lewis Pair Catalysts for Metal-Free and Selective Hydrogenation.Pure Appl. Chem . 2011 , 83 , 667–675. (c) Erker,
G. Frustrated Lewis Pairs: Some Recent Developments. Pure Appl.
Chem. 2012 , 84 , 2203–2217. (d) Paradies, J.,
Metal-Free Hydrogenation of Unsaturated Hydrocarbons Employing
Molecular Hydrogen. Angew. Chem., Int. Ed. 2014 ,53 , 3552–3557. (e) Stephan, D. W.; Frustrated Lewis Pairs:
From Concept to Catalysis. Acc. Chem. Res. 2015 ,48 , 306–316. (f) Stephan, D. W.; Erker, G. Frustrated Lewis
Pair Chemistry: Development and Perspectives. Angew. Chem., Int.
Ed. 2015 , 54 , 6400–6441. (g) Stephan, D. W.
Frustrated Lewis Pairs. J. Am. Chem. Soc . 2015 ,137 , 10018–10032. (h) Stephan, D. W. The Broadening Reach of
Frustrated Lewis Pair Chemistry. Science 2016 ,354 , aaf7229. (i) Wang, H.; Zheng, Y.; Pan, Z.; Fu, H.; Ling
F.; Zhong, W. Progress of Frustrated Lewis Pairs in Catalytic
Hydrogenation. Chin. J. Org. Chem. 2017 , 37 ,
301–313. (j) Li N.; Zhang, W.-X. Frustrated Lewis Pairs: Discovery
and Overviews in Catalysis. Chin. J. Chem. 2020 ,38 , 1360–1370. (k) Lam, J.; Szkop, K. M.; Mosaferi, E.;
Stephan, D. W. FLP Catalysis: Main Group Hydrogenations of Organic
Unsaturated Substrates. Chem. Soc. Rev. 2019 ,48 , 3592–3612. (l) Stephan, D. W. Diverse Uses of the Reaction
of Frustrated Lewis Pair (FLP) with Hydrogen. J. Am. Chem. Soc .2021 , 143 , 20002–20014.
- (a) Liu, Y.; Du, H. Frustrated Lewis Pair Catalyzed Asymmetric
Hydrogenation. Huaxue Xuebao 2014 , 72 , 771−777.
(b) Feng, X.; Du, H. Metal-Free Asymmetric Hydrogenation and
Hydrosilylation Catalyzed by Frustrated Lewis Pairs. Tetrahedron
Lett. 2014 , 55 , 6959−6964. (c) Shi, L.; Zhou, Y.-G.
Enantioselective Metal-Free Hydrogenation Catalyzed by Chiral
Frustrated Lewis Pairs. ChemCatChem 2015 , 7 ,
54−56. (d) Wilkins, L. C.; Melen, R. L. Enantioselective Main Group
Catalysis: Modern Catalysts for Organic Transformations. Coord.
Chem. Rev. 2016 , 324 , 123−129. (e) Paradies, J.
Chiral Borane-Based Lewis Acids for Metal Free Hydrogenations.Top. Organomet. Chem. 2017 , 62 , 193−216. (f)
Meng, W.; Feng, X.; Du, H. Lewis Pairs Catalyzed Asymmetric Metal-Free
Hydrogenations and Hydrosilylations. Acc. Chem. Res.2018 , 51 , 191−201. (g) Feng, X.; Meng, W.; Du, H.
Frustrated Lewis Pair Catalyzed Asymmetric Reactions. In Frustrated
Lewis Pairs; Molecular Catalysis, Vol 2; Slootweg, J. C., Jupp, A. R.,
Eds.; Springer Nature Switzerland AG: Cham, Switzerland, 2020; pp
29−86. (h) Feng, X.; Meng, W.; Du, H. Chiral Dienes: From Ligands to
FLP Catalysts. Chin. J. Chem. 2022 , 40 ,
1109−1116.
- (a) Chen, D.; Klankermayer, J. Metal-Free Catalytic Hydrogenation of
Imines with Tris(perfluorophenyl)borane. Chem. Commun.2008 , 2130−2131. (b) Chen, D.; Wang, Y.; Klankermayer, J.
Enantioselective Hydrogenation with Chiral Frustrated Lewis Pairs.Angew. Chem., Int. Ed. 2010 , 49 , 9475−9478. (c)
Ghattas, G.; Chen, D.; Pan, F.; Klankermayer, J. Asymmetric
Hydrogenation of Imines with a Recyclable Chiral Frustrated Lewis Pair
Catalyst. Dalton Trans. 2012 , 41 , 9026−9028.
(d) Liu, Y.; Du, H. Chiral Dienes as “Ligands” for Borane-Catalyzed
Metal-Free Asymmetric Hydrogenation of Imines. J. Am. Chem.
Soc. 2013 , 135 , 6810−6813. (e) Wei, S.; Du, H. A
Highly Enantioselective Hydrogenation of Silyl Enol Esters Catalyzed
by Chiral Frustrated Lewis Pairs. J. Am. Chem. Soc.2014 , 136 , 12261−12264. (f) Ren, X.; Li, G.; Wei, S.;
Du, H. Facile Development of Chiral Alkenylboranes from Chiral Diynes
for Asymmetric Hydrogenation of Silyl Enol Ethers. Org. Lett.2015 , 17 , 990−993. (g) Lindqvist, M.; Borre, K.;
Axenov, K.; Kótai, B.; Nieger, M.; Leskelä, M.; Pápai, I.; Repo, T.
Chiral Molecular Tweezers: Synthesis and Reactivity in Asymmetric
Hydrogenation. J. Am. Chem. Soc. 2015 , 137 ,
4038–4041. (h) Ye, K.-Y.; Wang, X.; Daniliuc, C. G.; Kehr, G.; Erker,
G. A Ferrocene-Based Phosphane/Borane Frustrated Lewis Pair for
Asymmetric Imine Reduction. Eur. J. Inorg. Chem. 2017 ,
368–371. (i) Tu, X. -S.; Zeng, N.-N.; Li, R.-Y.; Zhao, Y.-Q.; Xie,
D.-Z.; Peng, Q.; Wang, X.-C. C 2-Symmetric Bicyclic Bisborane
Catalysts: Kinetic or Thermodynamic Products of a Reversible
Hydroboration of Dienes. Angew. Chem., Int. Ed. 2018 ,57 , 15096–15100. (j) Gao, B.; Feng, X.; Meng, W.; Du, H.
Asymmetric Hydrogenations of Ketones and Enones with Chiral Lewis Base
Derived Frustrated Lewis Pairs. Angew. Chem., Int. Ed.2020 , 59 , 4498−4504.
- (a) Zhang, Z.; Du, H. Cis -Selective and Highly Enantioselective
Hydrogenation of 2,3,4-Trisubstituted Quinolines. Org. Lett.2015 , 17 , 2816−2819. (b) Zhang, Z.; Du, H.
Enantioselective Metal-Free Hydrogenations of Disubstituted
Quinolines. Org. Lett . 2015 , 17 , 6266−6269. (i)
Li, X.; Tian, J.-J.; Liu, N.; Tu, X.-S.; Zeng, N.-N.; Wang, X.-C.
Spiro-Bicyclic Bisborane Catalysts for Metal-Free Chemoselective and
Enantioselective Hydrogenation of Quinolines. Angew. Chem., Int.
Ed. 2019 , 58 , 4664−4668.
- Zhang, Z.; Du, H. A Highly cis -Selective and Enantioselective
Metal-Free Hydrogenation of 2,3-Disubstituted Quinoxalines.Angew. Chem., Int. Ed. 2015 , 54 , 623−626.
- CCDC 2297370 ESI.