Generic placeholder image

Current Organocatalysis

Author(s): Christian Trapp*, Corinna Herrmann, Chris Drewniok, Dieter Greif and Martin Hofrichter

DOI: 10.2174/2213337207666201207212540

DownloadDownload PDF Flyer Cite As
Diastereoselective Reduction of Selected α-substituted β-keto Esters and the Assignment of the Relative Configuration by 1H-NMR Spectroscopy

Page: [238 - 248] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Background: Chiral β-hydroxy esters and α-substituted β-hydroxy esters represent versatile building blocks for pheromones, β-lactam antibiotics and 1,2- or 1,3-aminoalcohols.

Objective: Synthesis of versatile α-substituted β-keto esters and their diastereoselective reduction to the corresponding syn- or anti-α-substituted β-hydroxy esters. Assignment of the relative configuration by NMR-spectroscopy after a Curtius rearrangement of α-substituted β-keto esters to 4-substituted 5-methyloxazolidin-2-ones.

Methods: Diastereoselective reduction was achieved by using different Lewis acids (zinc, titanium and cerium) in combination with complex borohydrides as reducing agents. Assignment of the relative configuration was verified by 1H-NMR spectroscopy after Curtius-rearrangement of α-substituted β-hydroxy esters to 4-substituted 5-methyloxazolidin-2-ones.

Results: For the syn-selective reduction, titanium tetrachloride (TiCl4) in combination with a pyridine-borane complex (py BH3) led to diastereoselectivities up to 99% dr. High anti-selective reduction was achieved by using cerium trichloride (CeCl3) and steric hindered reducing agents such as lithium triethylborohydride (LiEt3BH). After Curtius-rearrangement of each α-substituted β-hydroxy ester to the corresponding 4-substituted 5-methyloxazolidin-2-one, the relative configuration was confirmed by 1H NMR-spectroscopy.

Conclusion: We have expanded the procedure of Lewis acid-mediated diastereoselective reduction to bulky α-substituents such as the isopropyl group and the electron withdrawing phenyl ring.

Keywords: Diastereoselectivity, Keto esters, β-Hydroxy esters, Stereoselective reduction, NMR Spectroscopy, α-substituted.

Graphical Abstract

[1]
a) Kalaitzakis, D.; Smonou, I. Chemoenzymatic Synthesis of Stegobinone and Stegobiol, Components of the Natural Sex Pheromone of the Drugstore Beetle (Stegobium paniceum L.). Eur. J. Org. Chem., 2012, 2012, 43-46.
b) Zheng, J-F.; Lan, H-Q.; Yang, R-F.; Peng, Q-L.; Xiao, Z-H.; Tuo, S-C.; Hu, K-Z.; Xiang, Y-G.; Wei, Z.; Zhang, Z.; Huang, P-Q. Asymmetric Syntheses of the Sex Pheromones of Pine Sawflies, Their Homologs and Stereoisomers. Helv. Chim. Acta, 2012, 95, 1799-1808.
c) Mori, K. Synthesis of optically active pheromones. Tetrahedron, 1989, 45, 3233-3298.
[http://dx.doi.org/10.1002/ejoc.201101319]
[2]
Miller, M.J. Hydroxamate approach to the synthesis of. β.-lactam antibiotics. Acc. Chem. Res., 2002, 19, 49-56.
[3]
a) Bertau, M.; Bürli, M.; Hungerbühler, E.; Wagner, P. A novel highly stereoselective synthesis of chiral 5- and 4,5-substituted 2-oxazolidinones. Tetrahedron Asymmetry, 2001, 12, 2103-2107.
b) Didier, E.; Loubinoux, B.; Ramos Tombo, G.H.; Rihs, G. Chemo-enzymatic synthesis of 1,2- and 1,3- amino-alcohols and their use in the enantioselective reduction of acetophenone and anti-acetophenone oxime methyl ether with borane. Tetrahedron, 1991, 47, 4941-4958.
c) Ghosh, A.K.; Cho, H.; Onishi, M. Asymmetric alkylations and aldol reactions: (1S,2R)-2-aminocyclopentan-1-ol derived new chiral auxiliary. Tetrahedron Asymmetry, 1997, 8(6), 821-824.
d) Varga, A.; Zaharia, V.; Nógrádi, M.; Poppe, L. Chemoenzymatic synthesis of both enantiomers of 3-hydroxy- and 3-amino-3-phenylpropanoic acid. Tetrahedron Asymmetry, 2013, 24, 1389-1394.
[http://dx.doi.org/10.1016/S0040-4020(01)80959-5] [http://dx.doi.org/10.1016/S0957-4166(97)00065-7] [PMID: 30387787] [http://dx.doi.org/10.1016/j.tetasy.2013.09.007]
[4]
a) Bhuniya, R.; Mahapatra, T.; Nanda, S. Klebsiellapneumoniae (NBRC 3319) Mediated Asymmetric Reduction of α-Substituted β-Oxo Esters and Its Application to the Enantioiselective Synthesis of Small-Ring Carbocycle Derivatives. Eur. J. Org. Chem., 2012, 2012, 1597-1602.
b) Zhu, D.; Mukherjee, C.; Rozzell, J.D.; Kambourakis, S.; Hua, L. A recombinant ketoreductase tool-box. Assessing the substrate selectivity and stereoselectivity toward the reduction of β-ketoesters. Tetrahedron, 2006, 62, 901-905.
[http://dx.doi.org/10.1002/ejoc.201101695] [http://dx.doi.org/10.1016/j.tet.2005.10.044]
[5]
Victor, M.M.; Uchôa, J.E.; Riatto, V.B. First use of cactus and cushcush as biocatalysts in the enantioselective reduction of β -keto esters. Ind. Crops Prod., 2017, 96, 126-131.
[http://dx.doi.org/10.1016/j.indcrop.2016.11.048]
[6]
Stepankova, V.; Bidmanova, S.; Koudelakova, T.; Prokop, Z.; Chaloupkova, R.; Damborsky, J. Strategies for Stabilization of Enzymes in Organic Solvents. ACS Catal., 2013, 3, 2823-2836.
[http://dx.doi.org/10.1021/cs400684x]
[7]
a) Fernández-Ibáñez, M.Á.; Maciá, B.; Minnaard, A.J.; Feringa, B.L. Katalytische enantioselektive Reformatsky-Reaktionen mit Aldehyden. Angew. Chem., 2008, 120, 1337-1339.
b) Kholod, I.; Vallat, O.; Buciumas, A-M.; Neels, A.; Neier, R. Synthetic Strategies for the Synthesis and Transformation of Substituted Pyrrolinones as Advanced Intermediates for Rhazinilam Analogues. Eur. J. Org. Chem., 2014, 2014, 7865-7877.
c) Ramachandran, P.V.; Chanda, P.B. Enantioselective synthesis of anti- and syn-β-hydroxy-α-phenyl carboxylates via boron-mediated asymmetric aldol reaction. Chem. Commun. (Camb.), 2013, 49(30), 3152-3154.
[http://dx.doi.org/10.1002/ange.200704841] [http://dx.doi.org/10.1002/ejoc.201402903] [http://dx.doi.org/10.1039/c3cc40860d] [PMID: 23478288]
[8]
Noyori, R.; Ikeda, T.; Ohkuma, T.; Widhalm, M.; Kitamura, M.; Takaya, H.; Akutagawa, S.; Sayo, N.; Saito, T.; Taketomi, T.; Kumobayashi, H. Stereoselective hydrogenation via dynamic kinetic resolution. J. Am. Chem. Soc., 1989, 111, 9134-9135.
[http://dx.doi.org/10.1021/ja00207a038]
[9]
Marcantoni, E.; Alessandrini, S.; Malavolta, M.; Bartoli, G.; Bellucci, M.C.; Sambri, L.; Dalpozzo, R. Reversed Stereochemical Control in the Presence of CeCl(3) and TiCl(4) in the Lewis Acid Mediated Reduction of α-Alkyl-β-keto Esters by Metal Hydrides. A General Methodology for the Diastereoselective Synthesis of syn- and anti-α-Alkyl-β-hydroxy Esters. J. Org. Chem., 1999, 64(6), 1986-1992.
[http://dx.doi.org/10.1021/jo9821574] [PMID: 11674293]
[10]
Mandai, T.; Oshitari, T.; Susowake, M. Lipase-catalyzed Transesterification of Methyl 2-Substituted 3-Hydroxy-4-pentenoates and its Synthetic Application to the Taxol Side Chain. Synlett, 2002, 1665-1668
[http://dx.doi.org/10.1055/s-2002-34247]
[11]
Gu, G.; Lu, J.; Yu, O.; Wen, J.; Yin, Q.; Zhang, X. Enantioselective and Diastereoselective Ir-Catalyzed Hydrogenation of α-Substituted β-Ketoesters via Dynamic Kinetic Resolution. Org. Lett., 2018, 20(7), 1888-1892.
[http://dx.doi.org/10.1021/acs.orglett.8b00433] [PMID: 29557666]
[12]
Bartoli, G.; Bartolacci, M.; Giuliani, A.; Marcantoni, E.; Massaccesi, M. Diastereoselective Lewis Acid Mediated Reductions of α-Alkyl-β-Functionalized Carbonyl Compounds. Eur. J. Org. Chem., 2005, 2005, 2867-2879.
[http://dx.doi.org/10.1002/ejoc.200500038]
[13]
Zeevaart, J.G.; Parkinson, C.J.; de Koning, C.B. Copper(I) iodide- catalysed arylation of acetoacetate to yield 2-arylacetic acid esters. Tetrahedron Lett., 2007, 48, 3289-3293.
[http://dx.doi.org/10.1016/j.tetlet.2007.02.136]
[14]
a) Julian, P.L.; Oliver, J.J.; Kimball, R.H.; Pike, A.B.; Jefferson, G.D. a-PHENYLACETOACETONITRILE. Org. Synth., 1938, 18, 66.
b) Kimball, R.H.; Jefferson, G.D.; Pike, A.B. ETHYL a-PHENYLACETOACETATE. Org. Synth., 1938.
[15]
Peng, C.; Wang, Y.; Wang, J. Palladium-catalyzed cross-coupling of α-diazocarbonyl compounds with arylboronic acids. J. Am. Chem. Soc., 2008, 130(5), 1566-1567.
[http://dx.doi.org/10.1021/ja0782293] [PMID: 18186640]
[16]
Smith, A.M.; Billen, D.; Hii, K.K. Palladium-catalysed enantioselective α-hydroxylation of β-ketoesters. Chem. Commun. (Camb.), 2009, 3925-3927(26), 3925-3927.
[http://dx.doi.org/10.1039/b907151b] [PMID: 19662254]
[17]
a) Ito, Y.; Yamaguchi, M. Stereoselective reduction of 3-oxo amides with zinc borohydride. Tetrahedron Lett., 1983, 24, 5385-5386.
b) Nakata, T.; Oishi, T. Stereoselective reduction of β-keto esters with zinc borohydride. stereoselective synthesis of -3-hydroxy-2-alkylpropionates. Tetrahedron Lett., 1980, 21, 1641-1644.
c) Sato, T.; Nishio, M.; Otera, J. Unusual anti-Selective Reduction of α-Methyl β-Alkylketo Esters by Organotin Hydride-Titanium Tetrachloride. Synlett, 1995, 1995, 965-966.
[http://dx.doi.org/10.1016/S0040-4039(00)87875-2] [http://dx.doi.org/10.1016/S0040-4039(00)77774-4] [http://dx.doi.org/10.1055/s-1995-5136]
[18]
Oishi, T.; Nakata, T. Zinc Borohydride Encyclopedia of Reagents for Organic Synthesis, 2001.
[http://dx.doi.org/10.1002/047084289X.rz004]
[19]
Meier, H.; Krause, V. Einfluß der Enolisierung auf die Reduktion von β Ketocarbonsäure-Derivaten mit Zinkborhydrid / Influence of the Enol Formation on the Reduction of β-Keto Carboxylic Acid Derivatives by Zinc Borohydride. Z. Naturforsch. B, 1991, 46, 1714-.
[http://dx.doi.org/10.1515/znb-1991-1222]
[20]
Conlon, D.A.; Kumke, D.; Moeder, C.; Hardiman, M.; Hutson, G.; Sailer, L. Insights into the Cerium Chloride-Catalyzed Grignard Addition to Esters. Adv. Synth. Catal., 2004, 346, 1307-1315.
[http://dx.doi.org/10.1002/adsc.200404075]
[21]
Mulzer, J.; Zippel, M.; Brüntrup, G.; Segner, J.; Finke, J. Zur Stereochemie der Carbonsäuredianion-Aldehyd-Addition unter kinetisch und thermodynamisch kontrollierten Bedingungen — Reindarstellung und Konfigurationszuordnung von 2,3-disubstituiertenthreo- underythro-3-Hydroxycarbonsäuren. Liebigs Ann. Chem., 1980, 1980, 1108-1134.
[http://dx.doi.org/10.1002/jlac.198019800710]
[22]
Kalaitzakis, D.; Smonou, I. A convenient method for the assignment of relative configuration of acyclic α-alkyl-β-hydroxy carbonyl compounds by (1)H NMR. J. Org. Chem., 2008, 73(10), 3919-3921.
[http://dx.doi.org/10.1021/jo800066a] [PMID: 18410148]
[23]
Altona, C. Vicinal Coupling Constants and Conformation of Biomolecules. Encyclopedia of NMR, 2007, 4909-4923.
[http://dx.doi.org/10.1002/9780470034590.emrstm0587]
[24]
Navarro-Vázquez, A.; Cobas, J.C.; Sardina, F.J.; Casanueva, J.; Díez, E. A graphical tool for the prediction of vicinal proton-proton 3J(HH) coupling constants. J. Chem. Inf. Comput. Sci., 2004, 44(5), 1680-1685.
[http://dx.doi.org/10.1021/ci049913t] [PMID: 15446826]
[25]
Hünig, S.; Kreitmeier, P.; Märkl, G.; Sauer, J. Arbeitsmethoden in der organischen Chemie. Verlag Lehmanns; , 2006.
[26]
Dimitrov, V.; Kostova, K.; Genov, M. Anhydrous cerium(III) chloride — Effect of the drying process on activity and efficiency. Tetrahedron Lett., 1996, 37, 6787-6790.
[http://dx.doi.org/10.1016/S0040-4039(96)01479-7]