We have identified a novel one-pot method for the synthesis of β-amino alcohols, which is based on C-H bond hydroxylation at the benzylic α-carbon atom with a subsequent nitrile or amide functional group reduction. This cascade process uses molecular oxygen as an oxidant and sodium bis(2-methoxyethoxy)aluminum hydride as a reductant. The substrate scope was examined on 30 entries and, although the respective products were provided in moderate yields only, the above simple protocol may serve as a direct and powerful entry to the sterically congested 1,2-amino alcohols that are difficult to prepare by other routes. The plausible mechanistic rationale for the observed results is given and the reaction was applied to a synthesis of a potentially bioactive target.

Department of Chemical Drugs Faculty of Pharmacy Masaryk University Palackeho 1946 1 612 42 Brno Czech Republic

See more in PubMed

Nguyen L. A. He H. Pham-Huy C. Int. J. Biomed. Sci. 2006;2:85. PubMed PMC

Smith S. W. Toxicol. Sci. 2009;110:4. doi: 10.1093/toxsci/kfp097. PubMed DOI

Brooks W. H. Guida W. C. Daniel K. G. Curr. Top. Med. Chem. 2011;11:760. doi: 10.2174/156802611795165098. PubMed DOI PMC

Hyneck M., Dent J., Hook J. B., Ariens E. J. and Davies D. S., in Chirality in Drug Design and Synthesis, ed. C. Brown, Academic Press, San Diego, 1st edn, 2013, pp. 1–51

Ager D. J. Prakash I. Schaad D. R. Chem. Rev. 1996;96:835. doi: 10.1021/cr9500038. PubMed DOI

Bergmeier S. C. Tetrahedron. 2000;56:2561. doi: 10.1016/S0040-4020(00)00149-6. DOI

Lee H.-S. Kang S. H. Synlett. 2004:1673. doi: 10.1055/s-2004-829578. DOI

Giorgio Della S. Alessio R. Alessandra L. Curr. Org. Chem. 2011;15:2147. doi: 10.2174/138527211796150741. DOI

Nakano H. Owolabi I. A. Chennapuram M. Okuyama Y. Kwon E. Seki S. Tokiwa M. Takeshita M. Heterocycles. 2018;97:647. doi: 10.3987/REV-18-SR(T)3. PubMed DOI PMC

Karjalainen O. K. Koskinen A. M. P. Org. Biomol. Chem. 2012;10:4311. doi: 10.1039/C2OB25357G. PubMed DOI

Sehl T. Maugeri Z. Rother D. J. Mol. Catal. B: Enzym. 2015;114:65. doi: 10.1016/j.molcatb.2014.12.005. DOI

Gupta P. Mahajan N. New J. Chem. 2018;42:12296. doi: 10.1039/C8NJ00485D. DOI

Vol. 8: Reduction, in Comprehensive Organic Synthesis , ed. J. Clayden, Elsevier Science, Amsterdam, 2nd edn, 2014

Cossy J. Gomez Pardo D. Dumas C. Mirguet O. Déchamps I. Métro T.-X. Burger B. Roudeau R. Appenzeller J. Cochi A. Chirality. 2009;21:856. doi: 10.1002/chir.20716. PubMed DOI

Métro T.-X. Duthion B. Gomez Pardo D. Cossy J. Chem. Soc. Rev. 2010;39:89. doi: 10.1039/B806985A. PubMed DOI

Weng C. Zhang H. Xiong X. Lu X. Zhou Y. Asian J. Chem. 2014;26:3761. doi: 10.14233/ajchem.2014.16015. DOI

Bhagavathula D. S. Boddeti G. Venu R. J. Chem. 2017;6:27.

Donohoe T. J. Callens C. K. A. Flores A. Lacy A. R. Rathi A. H. Chem.–Eur. J. 2011;17:58. doi: 10.1002/chem.201002323. PubMed DOI

Taniguchi T. Yajima A. Ishibashi H. Adv. Synth. Catal. 2011;353:2643. doi: 10.1002/adsc.201100315. DOI

Hofmann D. de Salas C. Heinrich M. R. ChemSusChem. 2015;8:3167. doi: 10.1002/cssc.201500188. PubMed DOI

Heravi M. M. Lashaki T. B. Fattahi B. Zadsirjan V. RSC Adv. 2018;8:6634. doi: 10.1039/C7RA12625E. PubMed DOI PMC

Burchak O. N. Py S. Tetrahedron. 2009;65:7333. doi: 10.1016/j.tet.2009.06.003. DOI

Fisher G. B. Goralski C. T. Nicholson L. W. Hasha D. L. Zakett D. Singaram B. J. Org. Chem. 1995;60:2026. doi: 10.1021/jo00112a026. DOI

Kamimura A. Ono N. Tetrahedron Lett. 1989;30:731. doi: 10.1016/S0040-4039(01)80295-1. DOI

Tsay S.-C. Patel H. V. Hwu J. R. Synlett. 1998:939. doi: 10.1055/s-1998-1827. DOI

Diner P. Nielsen M. Bertelsen S. Niess B. Jørgensen K. A. Chem. Commun. 2007:3646. doi: 10.1039/B707844G. PubMed DOI

Russo A. Lattanzi A. Adv. Synth. Catal. 2008;350:1991. doi: 10.1002/adsc.200800387. DOI

Brunker H.-G. Adam W. J. Am. Chem. Soc. 1995;117:3976. doi: 10.1021/ja00119a012. DOI

Adam W. Brunker H.-G. Synthesis. 1995:1066. doi: 10.1055/s-1995-4071. DOI

Otevrel J. Bobal P. Synthesis. 2017;49:593.

Otevrel J. Bobal P. J. Org. Chem. 2017;82:8342. doi: 10.1021/acs.joc.7b00079. PubMed DOI

Otevrel J. Svestka D. Bobal P. Org. Biomol. Chem. 2019;17:5244. doi: 10.1039/C9OB00884E. PubMed DOI

Vit J., Casensky B. and Machacek J., Patent FR 1515582, Czechoslovak Academy of Sciences, 1968; Chem. Abstr., 1969, 70, 115009

Strouf O., Casensky B. and Kubanek V., Sodium Dihydrido-bis(2-methoxyethoxo)-aluminate (SDMA): A Versatile Organometallic Hydride, Elsevier, Amsterdam, 1985

Malek J. Org. React. 1985;34:1.

Malek J. Org. React. 1988;36:249.

Gugelchuk M., Silva III L. F., Vasconcelos R. S. and Quintiliano S. A. P., Bis(2-methoxyethoxy)aluminum Hydride, in Encyclopedia of Reagents for Organic Synthesis, ed. P. Fuchs, J. Bode, A. Charette and T. Rovis, John Wiley, New York, 2007

Rathi A. Synlett. 2010:1140. doi: 10.1055/s-0029-1219578. DOI

Smith M. B., Organic Synthesis, Elsevier Science, Cambridge, 2016, pp. 339–344

Bajwa N. Jennings M. P. J. Org. Chem. 2008;73:3638. doi: 10.1021/jo800150x. PubMed DOI

von Kieseritzky F. Lindstrom J. Tetrahedron Lett. 2011;52:4558. doi: 10.1016/j.tetlet.2011.06.092. DOI

Miyamoto K. Hoque M. M. Ogasa S. J. Org. Chem. 2012;77:8317. doi: 10.1021/jo300947h. PubMed DOI

Wu J. Xiao J. Dai W. Cao S. RSC Adv. 2015;5:34498. doi: 10.1039/C5RA04221F. DOI

Sun R. Liu J. Yang S. Chen M. Sun N. Chen H. Xie X. You X. Li S. Liu Y. Chem. Commun. 2015;51:6426. doi: 10.1039/C5CC00950B. PubMed DOI

Jeon H. H. Son J. B. Choi J. H. Jeong I. H. Tetrahedron Lett. 2007;48:627. doi: 10.1016/j.tetlet.2006.11.111. DOI

Konno T. Kishi M. Ishihara T. Yamada S. J. Fluorine Chem. 2013;156:144. doi: 10.1016/j.jfluchem.2013.09.010. DOI

Jin G. Zhang J. Wu W. Cao S. J. Fluorine Chem. 2014;168:240. doi: 10.1016/j.jfluchem.2014.10.010. DOI

Kraus M. Collect. Czech. Chem. Commun. 1972;37:3052. doi: 10.1135/cccc19723052. DOI

Czakoova M. Hetflejs J. Vcelak J. React. Kinet. Catal. Lett. 2001;72:277. doi: 10.1023/A:1010590812641. DOI

Bazant V. Capka M. Cerny M. Chvalovsky V. Kochloefl K. Kraus M. Malek J. Tetrahedron Lett. 1968;9:3303. doi: 10.1016/S0040-4039(00)89552-0. DOI

Cerny M. Malek J. Capka M. Chvalovsky V. Collect. Czech. Chem. Commun. 1969;34:1033. doi: 10.1135/cccc19691033. DOI

Kharasch M. S. Sosnovsky G. Tetrahedron. 1958;3:97. doi: 10.1016/0040-4020(58)80001-0. DOI

Kharasch M. S. Sosnovsky G. Tetrahedron. 1958;3:105. doi: 10.1016/0040-4020(58)80002-2. DOI

Selikson J. S. Watt D. S. J. Org. Chem. 1975;40:267. doi: 10.1021/jo00890a032. DOI

Walling C., Autoxidation in Active Oxygen in Chemistry, ed. C. S. Foote, J. S. Valentine, A. Greenberg and J. F. Liebman, Springer, Dordrecht, 1995, pp. 24–65

Bergstrasser U., Collier S. J., Ito Y., Kanemasa S. and Murahashi S. I., Three Carbon–Heteroatom Bonds: Nitriles, Isocyanides, and Derivatives in Science of Synthesis: Houben-Weyl Methods of Molecular Transformations, ed. S. I. Murahashi, Georg Thieme, Stuttgart, 2004, vol. 19

Moller M. Husemann M. Boche G. J. Organomet. Chem. 2001;624:47. doi: 10.1016/S0022-328X(00)00596-9. DOI

Bender D. M., Cantrell B. E., Fray A. H., Jones W. D., Miller W. D., Mitchell D., Simon R. L., Zarrinmayeh H. and Zimmerman D. M., Patent WO 2000066546, Eli Lilly, 2000Chem. Abstr., 2000, 133, 350055

Clemens J. A. and Lodge D., Patent WO 2002032389, Eli Lilly, 2002Chem. Abstr., 2002, 136, 340487

Sommer L. H. Frye C. L. Parker G. A. Michael K. W. J. Am. Chem. Soc. 1964;86:3271. doi: 10.1021/ja01070a014. DOI

Amir M. Kumar H. Javed S. A. Arch. Pharm. 2007;340:577. doi: 10.1002/ardp.200700065. PubMed DOI

Ohtsuka N. Okuno M. Hoshino Y. Honda K. A. Org. Biomol. Chem. 2016;14:9046. doi: 10.1039/C6OB01178K. PubMed DOI

Kerdesky F. A. J. Brooks C. D. W. Hulkower K. I. Bouska J. B. Bell R. L. Bioorg. Med. Chem. 1997;5:393. doi: 10.1016/S0968-0896(96)00255-6. PubMed DOI

Tu T. Wang Z. Liu Z. Feng X. Wang Q. Green Chem. 2012;14:921. doi: 10.1039/C2GC16637B. DOI

Kanda T. Naraoka A. Naka H. J. Am. Chem. Soc. 2019;141:825. doi: 10.1021/jacs.8b12877. PubMed DOI

Mecca T. Superchi S. Giorgio E. Rosini C. Tetrahedron: Asymmetry. 2001;12:1225. doi: 10.1016/S0957-4166(01)00199-9. DOI

Kimura M. Kuboki A. Sugai T. Tetrahedron: Asymmetry. 2002;13:1059. doi: 10.1016/S0957-4166(02)00242-2. DOI

Bonner W. A. J. Am. Chem. Soc. 1954;76:6350. doi: 10.1021/ja01653a031. DOI

Iqbal N. Cho E. J. Adv. Synth. Catal. 2015;357:2187. doi: 10.1002/adsc.201500257. DOI

Bellale E. V. Bhalerao D. S. Akamanchi K. G. J. Org. Chem. 2008;73:9473. doi: 10.1021/jo801580g. PubMed DOI

Nemeth G. Rakoczy E. Simig G. J. Fluorine Chem. 1996;76:91. doi: 10.1016/0022-1139(95)03338-6. DOI

Dale J. A. Dull D. L. Mosher S. H. J. Org. Chem. 1969;34:2543. doi: 10.1021/jo01261a013. DOI

Li F. Zou X. Wang N. Adv. Synth. Catal. 2015;357:1405. doi: 10.1002/adsc.201401013. DOI

Guo B. de Vries J. G. Otten E. Chem. Sci. 2019;10:10647. doi: 10.1039/C9SC04624K. PubMed DOI PMC

Xia H.-M. Zhang F.-L. Ye T. Wang Y.-F. Angew. Chem., Int. Ed. 2018;57:11770. doi: 10.1002/anie.201804794. PubMed DOI

Khan N. H. Agrawal S. Kureshy R. I. Abdi S. H. R. Singh S. Jasra R. V. J. Organomet. Chem. 2007;692:4361. doi: 10.1016/j.jorganchem.2007.07.011. DOI

Gassman P. G. Talley J. J. Org. Synth. 1981;60:14. doi: 10.15227/orgsyn.060.0014. DOI

Hiyama T. Inoue M. Saito K. Synthesis. 1986:645. doi: 10.1055/s-1986-31732. DOI

Shang R. Ji D.-S. Chu L. Fu Y. Liu L. Angew. Chem., Int. Ed. 2011;50:4470. doi: 10.1002/anie.201006763. PubMed DOI

Xiao J. Wong Z. Z. Lu Y. P. Loh T. P. Adv. Synth. Catal. 2010;352:1107. doi: 10.1002/adsc.200900908. DOI

Dornow A. Sassenberg W. Justus Liebigs Ann. Chem. 1955;594:185. doi: 10.1002/jlac.19555940303. DOI

Balaramnavar V. M. Srivastava R. Rahuja N. Gupta S. Rawat A. K. Varshney S. Chandasana H. Chhonker Y. S. Doharey P. K. Kumar S. Gautam S. Srivastava S. P. Bhatta R. S. Saxena J. K. Gaikwad A. N. Srivastava A. K. Saxena A. K. Eur. J. Med. Chem. 2014;87:578. doi: 10.1016/j.ejmech.2014.09.097. PubMed DOI

Casey C. P. Guan H. J. Am. Chem. Soc. 2007;129:5816. doi: 10.1021/ja071159f. PubMed DOI

Castell J. V. Gomez-Lechon M. J. Miranda M. A. Morera I. M. J. Photochem. Photobiol., B. 1992;13:71. doi: 10.1016/1011-1344(92)80041-S. PubMed DOI

Riley D. P. Getman D. P. Beck G. R. Heintz R. M. J. Org. Chem. 1987;52:287. doi: 10.1021/jo00378a027. DOI

New potent N-hydroxycinnamamide-based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP-1 leukaemia cells