Hafnium(IV) Chloride Catalyzes Highly Efficient Acetalization of Carbonyl Compounds

Author(s): Israel Bonilla-Landa, Emizael López-Hernández, Felipe Barrera-Méndez, Nadia C. Salas, José L. Olivares-Romero*.

Journal Name: Current Organic Synthesis

Volume 16 , Issue 6 , 2019

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Abstract:

Background: Hafnium(IV) tetrachloride efficiently catalyzes the protection of a variety of aldehydes and ketones, including benzophenone, acetophenone, and cyclohexanone, to the corresponding dimethyl acetals and 1,3-dioxolanes, under microwave heating. Substrates possessing acid-labile protecting groups (TBDPS and Boc) chemoselectively generated the corresponding acetal/ketal in excellent yields.

Aims and Objectives: In this study. the selective protection of aldehydes and ketones using a Hafnium(IV) chloride, which is a novel catalyst, under microwave heating was observed. Hence, it is imperative to find suitable conditions to promote the protection reaction in high yields and short reaction times. This study was undertaken not only to find a novel catalyst but also to perform the reaction with substrates bearing acid-labile protecting groups, and study the more challenging ketones as benzophenone.

Materials and Methods: Using a microwave synthesis reactor Monowave 400 of Anton Paar, the protection reaction was performed on a raging temperature of 100°C ±1, a pressure of 2.9 bar, and an electric power of 50 W. More than 40 substrates have been screened and protected, not only the aldehydes were protected in high yields but also the more challenging ketones such as benzophenone were protected. All the products were purified by simple flash column chromatography, using silica gel and hexanes/ethyl acetate (90:10) as eluents. Finally, the protected substrates were characterized by NMR 1H, 13C and APCI-HRMS-QTOF.

Results: Preliminary screening allowed us to find that 5 mol % of the catalyst is enough to furnish the protected aldehyde or ketone in up to 99% yield. Also it was found that substrates with a variety of substitutions on the aromatic ring (aldehyde or ketone), that include electron-withdrawing and electrondonating group, can be protected using this methodology in high yields. The more challenging cyclic ketones were also protected in up to 86% yield. It was found that trimethyl orthoformate is a very good additive to obtain the protected acetophenone. Finally, the protection of aldehydes with sensitive functional groups was performed. Indeed, it was found that substrates bearing acid labile groups such as Boc and TBDPS, chemoselectively generated the corresponding acetal/ketal compound while keeping the protective groups intact in up to 73% yield.

Conclusion: Hafnium(IV) chloride as a catalyst provides a simple, highly efficient, and general chemoselective methodology for the protection of a variety of structurally diverse aldehydes and ketones. The major advantages offered by this method are: high yields, low catalyst loading, air-stability, and non-toxicity.

Keywords: Hafnium(IV) tetrachloride, Lewis acid, catalyst, acetalization, microwave reaction, carbonyl compounds.

[1]
a)Greene, T.W. Protection for the Carbonyl Group. In: Greene’s Protective Groups in Organic Synthesis, 5th ed; Wuts, P.G.M., Ed.; Wiley: New York, 2014, pp. 554-684.
b)Sandler, S.R.; Karo, W. Organic Functional Group Preparations, 2nd ed; Academic: New York, 1989, Vol. III, .
c)Meskens, F.A.J. Methods for the preparation of acetals from alcohols or oxiranes and carbonyl compounds. Synthesis, 1981, 501-522.
[http://dx.doi.org/10.1055/s-1981-29507]
d)Macpherson, D.T.; Harshad, K.R. Monocoordinated carbon functions. In: Comprehensive Organic Functional Group Transformations. Katritzky, A.R.; MethChon, O.; Rees, C.W., Eds., Elsevier Science: Pergamon, 1995, Vol. 4.
[2]
Kocienski, P.J. Protecting Groups; 3rd ed; Gerg thieme Verlag: New York, 2004.
[3]
Wenkert, E.; Goodwin, T.E. 4-Formyl-2-cyclohexenone derivatives. Synth. Commun., 1977, 7, 409-415.
[http://dx.doi.org/10.1080/00397917708050773]
[4]
Cameron, A.F.B.; Hunt, J.S.; Oughton, J.F.; Wilkinson, P.A.; Wilson, B.M. Studies in the synthesis of cortisone. Part III. The degradation of the ergosterol side chain. J. Chem. Soc., 1953, 3864-3869.
[http://dx.doi.org/10.1039/jr9530003864]
[5]
Patwardhan, S.A.; Dev, S. Amberlyst-15, a superior catalyst for the preparation of enol ethers and acetals. Synthesis, 1974, 348-349.
[http://dx.doi.org/10.1055/s-1974-23314]
[6]
Ranu, B.C.; Jana, R.; Samanta, S. A simple, efficient and general procedure for acetalization of carbonyl compounds and deprotection of acetals under the catalysis of indium(III) chloride. Adv. Synth. Catal., 2004, 346, 446-450.
[http://dx.doi.org/10.1002/adsc.200303154]
[7]
Mirjalili, B.F.; Zolfigol, M.A.; Bamoniri, A.; Zarchi, K.; Zaghaghi, Z.; Parvaideh, M. An efficient protocol for acetalization of carbonyl compounds using Zr(HSO4)4 at room temperature under solvent-free conditions. J. Iran. Chem. Soc., 2007, 4, 340-346.
[http://dx.doi.org/10.1007/BF03245985]
[8]
Firouzabadi, H.; Iranpoor, N.; Karimi, B. Zirconium tetrachloride (ZrCl)4 catalyzed highly chemoselective and efficient acetalization of carbonyl compounds. Synlett, 1999, 3, 321-323.
[http://dx.doi.org/10.1055/s-1999-2605]
[9]
Ono, F.; Takenaka, H.; Fujikawa, T.; Mori, M.; Sato, T. A convenient method for converting hydroxyacetophenones into their ethylene or trimethylene acetals. Synthesis, 2009, 8, 1318-1322.
[http://dx.doi.org/10.1055/s-0028-1088025]
[10]
Gregg, B.T.; Golden, K.C.; Quinn, J.F. Indium(III) trifluoromethanesulfonate as a mild, efficient catalyst for the formation of acetals and ketals in the presence of acid sensitive functional groups. Tetrahedron, 2008, 64, 3287-3295.
[http://dx.doi.org/10.1016/j.tet.2008.01.118]
[11]
Ishihara, K.; Karumi, Y.; Kubota, M.; Yamamoto, H. Scandium trifluoromethanesulfonimide and scandium trifluoromethanesulfonate as extremely active acetalization catalyst. Synlett, 1996, 839-841.
[http://dx.doi.org/10.1055/s-1996-5594]
[12]
Leonard, N.M.; Oswald, M.C.; Freiberg, D.A.; Nattier, B.A.; Smith, R.C.; Mohan, R.S. A simple and versatile method for the synthesis of acetals from aldehydes and ketones using bismuth triflate. J. Org. Chem., 2002, 67(15), 5202-5207.
[http://dx.doi.org/10.1021/jo0258249] [PMID: 12126407]
[13]
Clerici, A.; Pastori, N.; Porta, O. Efficient acetalisation of aldehydes catalyzed by titanium tetrachloride in a basic medium. Tetrahedron, 1998, 54, 15679-15690.
[http://dx.doi.org/10.1016/S0040-4020(98)00982-X]
[14]
Kumar, R.; Chakraborti, A.K. Copper(II) tetrafluoroborate as a novel and highly efficient catalyst for acetal formation. Tetrahedron Lett., 2005, 46, 8319-8323.
[http://dx.doi.org/10.1016/j.tetlet.2005.09.168]
[15]
Hamada, N.; Kazahaya, K.; Shimizu, H.; Sato, T. An efficient and versatile procedure for the synthesis of acetals from aldehydes and ketones catalyzed by lithium tetrafluoroborate. Synlett, 2004, 6, 1074-1076.
[http://dx.doi.org/10.1055/s-2004-820038]
[16]
Gemal, A.L.; Luche, J.L. Lanthanoids in organic synthesis. 4. Selective ketalization and reduction of carbonyl groups. J. Org. Chem., 1979, 44, 4187-4189.
[http://dx.doi.org/10.1021/jo01337a038]
[17]
Some representative examples in the use of Hafnium as catalyst are: a) Shiina, I.; Suzuki, M.; Yokoyama, K. A convenient method for the synthesis of 4,4-diarylbut-1-enes via the successive allylation of aromatic aldehydes and the Friedel-Crafts alkylation reaction of aromatic nucleophiles with the intermediary benzyl silyl ethers using HfCl4 or Cl2Si(OTf)2. Tetrahedron Lett, 2002. 43, 6395-6398.
[http://dx.doi.org/10.1016/S0040-4039(02)01374-6]
b)Hayashi, Y.; Nakamura, M.; Nakai, S.; Inoue, T. The HfCl4-mediated Diels- Alder reaction of furan. Angew. Chem. Int. Ed, 2002. 41, 4079-4082.
[http://dx.doi.org/10.1002/1521-3773(20021104)41:214079::AID-ANIE4079>3.0.CO;2-N]
cHachiya, I.; Moriwaki, M.; Kobayashi, S. Hafnium(IV) trifluoromethanesulfonate, and efficient catalyst for the Friedel-Crafts acylation and alkylation reactions. Bull. Chem. Soc. Jpn, 1995. 68, 2053-2060.
[http://dx.doi.org/10.1246/bcsj.68.2053]
d)Ishihara, K.; Ohara, S.; Yamamoto, H. Condensation of carboxylic acids with alcohols catalyzed by Hafnium(IV) salts. Science, 2000. 290, 1140-1142.
[http://dx.doi.org/10.1126/science.290.5494.1140]
e)Noji, M.; Ohno, T.; Fuji, K.; Futaba, N.; Tajima, H.; Ishii, K. Secondary benzylation using benzyl alcohols catalyzed by lanthanoid, scandium, and hafnium triflate. J. Org. Chem, 2003. 68, 9340-9347.
[http://dx.doi.org/10.1021/jo034255h]
f)Hachiya, I.; Moriwaki, M.; Kobayashi, S. Catalytic Friedel-Crafts acylation reactions using hafnium triflate as a catalyst in lithium perchlorate-nitromethane. Tetrahedron Lett, 1995. 36, 409-412.
[http://dx.doi.org/10.1016/0040-4039(94)0221-V]
g)Olivares-Romero, J.L.; Li, Z.; Yamamoto, H. Hf(IV)-catalyzed enantioselective epoxidation of N-alkenyl sulfonamides and N-tosyl imines. J. Am. Chem. Soc, 2012. 134, 5440-5443
[http://dx.doi.org/10.1021/ja211880s]
h)Tsurugi, H.; Yamamoto, K.; Mashima, K. Oxidant-free direct coupling of internal alkynes and 2-alkylpyridine via double C-H activations by alkylhafnium complexes. J. Am. Chem. Soc, 2011. 133, 732-735.
[http://dx.doi.org/10.1021/ja1100118]
i)Olivares-Romero, J. L.; Li, Z.; Yamamoto, H. Catalytic enantioselective epoxidation of tertiary allylic and homoallylic alcohols. J. Am. Chem. Soc, 2013. 135, 3411-3413.
[http://dx.doi.org/10.1021/ja401182a]


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Article Details

VOLUME: 16
ISSUE: 6
Year: 2019
Page: [913 - 920]
Pages: 8
DOI: 10.2174/1570179416666190715100505
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