Montmorillonite Clay: A Novel Reagent for the

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Montmorillonite Clay: A Novel Reagent for the Chemoselective Hydrolysis of t-Butyl Esters MontmoriloniteClay:S. J. TheChemosel ctiveHydrYadav,* olysi oft-ButylEsters B. V. Subba Reddy, K. Sanjeeva Rao, K. Harikishan Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India Fax +91(40)7160512; E-mail: [email protected] Received 7 February 2002

Key words: solid acids, tert-butyl esters, a-amino acids

Protection of acids with appropriate protecting groups plays an important role in organic synthesis, especially in the synthesis of natural products.1 Carboxylic acids can be protected as anhydrides, amides or esters.2 However, the final stage of chemical process frequently requires their cleavage so as to regenerate the parent carboxylic acid. Among various acid protective groups, t-butyl esters are widely used in the synthesis of peptides, alkaloids and other natural products, because of their ease of formation and/or removal under specific conditions.3 Removal of tbutyl esters often involves the use of strong protic acids1,2 such as TFA and HCl as well as Lewis acids4 including ZnBr2, silyl triflates and CeCl3×7H2O–NaI.5–7 However, many of these procedures are of limited synthetic scope due to the lack of selectivity, the use of stoichiometric amount of reagents, corrosive and/or hazardous reagents, the requirement of high temperature or long reaction time and the necessity for anhydrous conditions. Moreover, no attempt has been made to recycle the catalyst thereby making the process economic and environmentally friendly. Thus, the development of new reagents that are more efficient and lead to convenient procedures and improved yields with good functional group compatibility is still of interest. In recent years, the use of solid acid catalysts such as clays and zeolites has received considerable attention in different areas of organic synthesis due to their environmental compatibility, recyclability, greater selectivity, non-corrosiveness, simplicity in operation, low cost and ease of isolation. In particular, clay catalysts render reaction processes convenient, more economic, environmentally benign and can act as Bronsted as well as Lewis acids in their natural or ion-exchanged forms, enabling them to function as efficient catalysts for various transformations. Synlett 2002, No. 5, 03 05 2002. Article Identifier: 1437-2096,E;2002,0,05,0826,0828,ftx,en;D02502ST.pdf. © Georg Thieme Verlag Stuttgart · New York ISSN 0936-5214

In this report, we wish to describe a simple and efficient method for the chemoselective hydrolysis of t-butyl esters in the presence of a wide range of functional groups using an inexpensive and reusable catalyst solid acid KSF clay. The t-butyl esters were smoothly deprotected to the parent carboxylic acids in the presence of montmorillonite KSF clay under mild reaction conditions (Scheme).

Scheme

The cleavage was affected by montmorillonite clay in refluxing acetonitrile. The deprotection proceeds efficiently in high yield with high chemoselectivity. This method selectively cleaves t-butyl esters leaving benzyl, methyl and allyl esters intact. Such selectivity can be applied in synthetic sequences in which two ester moieties must be unmasked at different stages of the synthesis. It should be noted that the t-butyl esters bearing a-stereogenic centers gave the parent acids with complete retention of the original configuration.8 This method is highly chemoselective for deprotecting tert-butyl esters without affecting the other functional groups. However, in the absence of catalyst, the reaction did not yield any product even after a long period in refluxing acetonitrile. The reactions are clean, and complete within 1.5–3.5 hours. Due to the short reaction time required for this cleavage, a number of functional groups, which are capable of reacting in the presence of clay, remain intact. The major advantage of this cleavage is in the selective removal of t-butyl esters in the presence of other acid sensitive protecting groups such as carbamates, esters and ethers, a selectivity is lacking in the reported procedures. t-Butyl esters were more rapidly deprotected than allyl ether and acetates by these conditions. Furthermore, the compatibility of this procedure is illustrated by the selective removal of a t-butyl group without affecting olefins, carbamates, ethers and halides. There are many advantages in the use of montmorillonite clay for this cleavage, which avoids the use of either strongly acidic or basic conditions. This method does not require the use of anhydrous conditions or solvents and no precautions need to be taken to exclude moisture from the reaction medium. Thus, the present method is mild and tolerates a wide range of functional groups. As evident

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Abstract: A mild and highly selective hydrolysis of t-butyl esters has been achieved in high yields using montmorillonite KSF in refluxing acetonitrile. The method is compatible with a variety of protecting and functional groups such as BOC, Cbz, propargyl, allyl, benzyl, t-butyl ethers, allyl, methyl and benzyl esters present in the molecule.

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Montmorillonite Clay: The Chemoselective Hydrolysis of t-Butyl Esters

from the Table, acid sensitive protecting groups such as Ac, BOC, Cbz, PMB and allyl ethers survive under the reaction conditions. Other carboxylic acid protecting groups such as amides, alkyl and benzyl esters are stable to the present reaction conditions. Finally, the clay can be recovered by filtration, washed with methanol and recycled in subsequent reactions (after activation at 120 °C for 4–5 hours) with gradual decrease in activity; for example, tbutyl cinnamate gave 95%, 87% and 81% yields of cinnamic acid over three cycles. These results clearly show

the advantage of this method over Lewis acid catalyzed procedures. In summary, this paper describes a mild and efficient method for the selective hydrolysis of t-butyl esters to their parent carboxylic acids using reusable solid acid KSF clay, thereby leaving acid- and base-labile protecting groups intact. The high levels of chemoselectivity in this process combined with a simple operation, high yields and ready availability of reagents at low cost will find a wider use of the t-butyl protective group in organic synthesis.

KSF Clay Catalyzed Selective Hydrolysis of t-Butyl Esters Reaction time (h)

Yieldb (%)

a

3.0

93

b

3.5

89

c

3.0

80

d

4.0

90

e

4.5

85

f

3.0

87

g

3.0

90

h

3.5

92

i

4.0

89

j

3.0

95

k

5.5

85

l

5.0

80

m

4.5

87

Entry

a b

Ester 1

Acida 2

All products were characterized by 1H NMR, IR and mass spectroscopy. Isolated and unoptimized yields.

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© Thieme Stuttgart · New York


Table

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J. S. Yadav et al.

Acknowledgement BVS, KSR and KH thank CSIR, New Delhi for the award of fellowships.

References (1) Kocienski, P. J. Protecting Groups; Thieme: Stuttgart, 1994, 125–128. (2) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John Wiley and Sons: New York, 1999. (3) (a) Anderson, G. W.; Callahan, F. M. J. Org. Chem. 1960, 82, 3359. (b) Jackson, R. W. Tetrahedron Lett. 2001, 42, 5163. (4) Wu, Y. Q.; Limburg, D. C.; Wilkinson, D. E.; Vaal, M. J.; Hamilton, G. S. Tetrahedron Lett. 2000, 41, 2847. (5) (a) Jones, A. B.; Villalobos, A.; Linde, R. G. II.; Danishefsky, S. J. J. Org. Chem. 1990, 55, 2786. (b) Marcantoni, E.; Massaccesi, M.; Torregiani, E.; Bartoli, G.; Bosco, M.; Sambri, L. J. Org. Chem. 2001, 66, 4430. (6) (a) Balogh, M.; Laszlo, P. In Organic Chemistry using Clays; Spinger-Verlag: Berlin, 1993; and references cited therein. (b) Cornelis, A.; Laszlo, P. Synlett 1994, 155. (7) (a) Yadav, J. S.; Reddy, B. V. S.; Kumar, G. M.; Murthy, Ch. V. S. R. Tetrahedron Lett. 2001, 42, 89. (b) Yadav, J. S.; Reddy, B. V. S.; Rasheed, M.; Kumar, H. M. S. Synlett 2000, 487. (c) Kumar, H. M. S.; Reddy, B. V. S.; Mohanty, P. K.; Yadav, J. S. Tetrahedron Lett. 1997, 38, 3619. (d) Yadav, J. S.; Reddy, B. V. S.; Madan, Ch. Synlett 2001, 1131.

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(8) Experimental procedure: A mixture of t-butyl ester (5 mmol), KSF clay (1.0 g) in acetonitrile (10 mL) was stirred at reflux temperature for a specified time as required to complete the reaction (Table). After complete conversion, as indicated by TLC, the reaction mixture was filtered and washed with ethyl acetate (2 ´ 15 mL). The combined organic layers were dried over anhydrous Na2SO4, concentrated in vacuo and purified by column chromatography on silica gel (Merck, 100–200 mesh, ethyl acetate–hexane, 2:8) to afford pure acid. Spectroscopic data for the selected compounds: 1a: Liquid, 1 H NMR (CDCl3): d 1.45 (s, 9 H), 3.40 (s, 2 H), 3.83 (s, 3 H), 3.85 (s, 3 H), 6.75–6.78 (m, 3 H). EIMS: m/z: 252 [M+]; IR (KBr): 3031, 2968, 1725, 1527, 1458, 1205, 1070, 915, 727 cm–1. 2a: Solid, mp 95–97 °C; 1H NMR (CDCl3): d 3.57 (s, 2 H), 3.83 (s, 3 H), 3.85 (s, 3 H), 6.75–6.78 (m, 3 H). EIMS: m/z: 196 [M+]; IR (KBr): 3345, 3031, 2968, 1695, 1527, 1458, 1205, 1070, 915, 727 cm–1. 1l: Liquid, 1H NMR (CDCl3): d 1.40 (d, 3 H, J = 6.8 Hz), 1.43 (s, 9 H), 4.38 (m, 1 H), 5.10 (s, 2 H), 5.45 (brs, NH), 7.37–7.40 (m, 5 H). EIMS: m/z: 279 [M+]; IR (KBr): 3342, 3035, 2965, 1724, 1525, 1453, 1209, 1065, 917, 735 cm–1. 2l: Solid, [a]D20 –14.0 (c = 2.0, AcOH), Aldrich, [a]D23 –14.2 (c = 2.0, AcOH). 1H NMR (DMSO-d6): d 1.48 (d, 3 H, J = 7.0 Hz), 4.40 (m, 1 H), 5.18 (s, 2 H), 5.27 (brs, NH), 7.28–7.40 (m, 5 H), 8.15 (brs, OH). EIMS: m/z: 223 [M+]; IR (KBr): 3347, 3036, 1695, 1536, 1458, 1252, 1075, 1027, 914, 739 cm–1.

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