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debenzylation of aryl ethers
Tetrahedron Letters 54 (2013) 4540–4543
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
NiCl26H2O/NaBH4 in methanol: a mild and efficient strategy for chemoselective deallylation/debenzylation of aryl ethers Mangilal Chouhan a, Kapil Kumar a, Ratnesh Sharma a, Vikas Grover b, Vipin A. Nair a,⇑ a b
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, Mohali, Punjab 160062, India Central Instrumentation Laboratory, National Institute of Pharmaceutical Education and Research, Sector 67, Mohali, Punjab 160062, India
a r t i c l e
i n f o
Article history: Received 2 May 2013 Revised 12 June 2013 Accepted 15 June 2013 Available online 24 June 2013
a b s t r a c t Deprotection of allyl/benzyl aryl ethers was achieved chemoselectively. The mild and inexpensive reagent combination of NiCl26H2O/NaBH4 in methanol afforded the products in high yields, within a reaction time of 5–10 min. Ó 2013 Elsevier Ltd. All rights reserved.
Keywords: Nickel chloride hexahydrate Sodium borohydride Debenzylation Deallylation Chemoselectivity
Selective protection and deprotection of functional groups is an art and challenge in the synthesis of complex organic molecules. Of the various kinds of protections available for alcohols/phenols,1,2 ethers are widely preferred owing to their stability towards nucleophiles and bases. A number of reagents are used to cleave primary alkyl aryl ethers such as BBr3,3 EtSNa/DMF,4 TMSI5 and BCl3/n-Bu4NI.6 Although simple alkyl groups serve as effective protecting groups, deprotection requires strongly electrophilic reagents/conditions. Because of their stability, t-butyl ethers are cleaved under moderately acidic conditions using either CF3COOH7 or FeCl3 in (CH3CO)2O.8 The allyl group, usually stable under basic and acidic conditions, is another widely used protecting group for alcohols and phenols. Methods for regeneration of alcohols from allylic ethers include DDQ,9 NaBH4/I2,10 Me3SiCl/NaI,11 CeCl37H2O/NaI12 or Pd/C/H2.13 Cleavage of allyl groups has been reported using PdCl2/CuCl/DMF–H2O/O214 or with DIBAL and catalytic NiCl2(dppp).15 The benzyl group can be used for the protection of the hydroxy groups when acidic conditions for ether cleavage are not tolerated. The benzyl protection is removed either by using Pd/C/H2,16 Pd/C/TES,17 I2/TES,18 NaBrO3/Na2S2O419 or with Na+ or K+ in NH3.20 Lewis acids21 such as FeCl3 and SnCl4 also afford alcohols from benzyl ethers. The cleavage of inert aryl ethers using different Ni salts is also reported.22 Though several methods are available for the deprotection of ethers, the limitations imposed by the substrates/reagents/procedures provide sufficient scope ⇑ Corresponding author. Tel.: +91 172 229 2045; fax: +91 172 221 4692. E-mail addresses: [email protected], [email protected] (V.A. Nair). 0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2013.06.072
Scheme 1. Debenzylation of aryl benzyl ether.
Table 1 Effect of metal saltsa
a
Entry
Metal salts (equiv)
NaBH4 (equiv)
Time (min)
Yield (%)
1 2 3 4 5 6 7 8 9 10
— NiCl26H2O (1.0) FeCl3 (1.0) CoCl26H2O (1.0) NiCl26H2O (1.0) PdCl2 (1.0) CuCl (1.0) NiCl26H2O (1.5) NiCl26H2O (1.5) NiCl26H2O (1.5)
1.0 — 1.0 1.0 1.0 1.0 1.0 2.0 3.0 4.0
30 30 30 30 15 30 30 15 5 5
— — 20 45 70 46 Trace 85 92 93
Benzyloxybenzene (1.0 equiv), methanol (5 mL).
for the development of newer methods. Based on our interests in reaction methodology23 we were in search of a suitable strategy for selective protection–deprotection of polyhydroxy compounds,
4541
M. Chouhan et al. / Tetrahedron Letters 54 (2013) 4540–4543 Table 2 Effect of solventsa
a
Entry
Solvent
Time (min)
Yield (%)
1 2 3 4 5 6 7
Toluene MeCN DMF THF Water EtOH MeOH
30 30 30 30 30 30 5
— — — — 20 50 92
Benzyloxybenzene (1.0 equiv), NiCl26H2O (1.5 equiv), NaBH4 (3.0 equiv).
taking advantage of the variations in reactivity/environment of the hydroxy groups. Our efforts culminated in a mild and efficient procedure for the deprotection of aryl benzyl ethers and allyl aryl ethers using NiCl26H2O and NaBH4 in methanol to afford phenols. The chemoselectivity is demonstrated by the indolent reagent nature towards alkyl ethers. The procedure utilizes reagents that does not require prior preparation and has advantages such as neither strongly basic nor acidic conditions are required, no precautions to exclude moisture or air from the reaction, inexpensive reagents and excellent yields in a short reaction time of 5–10 min.
Table 3 Reactions of allyl/benzyl ethers with NiCl26H2O/NaBH4a Entry
Substrate
Product
Yieldb (%)
1
92
2
93
3
90
4
92
5
88
6
89
7
90
8
90
9
90
10
89
11
90
12
90
13
90
14
87
15
93
16
88
(continued on next page)
4542
M. Chouhan et al. / Tetrahedron Letters 54 (2013) 4540–4543
Table 3 (continued) Entry
a b
Substrate
Product
Yieldb (%)
17
88
18
92
Substrate (1.0 equiv), NiCl26H2O (1.5 equiv), NaBH4 (3.0 equiv), methanol (5 mL). Isolated yield.
Figure 1. Plausible reaction mechanism.
Scheme 2. Chemoselectivity of the reaction.
A detailed investigation was performed on benzyloxybenzene by reacting it with sodium borohydride and different metal salts in methanol at 0 °C (Scheme 1). Salts of transition metals such as Fe, Co, Ni, Pd and Cu were evaluated (Table 1). NiCl26H2O provided maximum yields of phenol in 5 min, while other metal salts gave inferior yields. An examination of the effect of the solvents on the outcome of the reaction indicated that non-polar and polar aprotic solvents did not facilitate the reaction while polar protic solvents such as water and ethanol showed an improvement (Table 2). The best result was obtained with methanol. From the above results we concluded that reacting 1.0 equiv of the benzyl protected phenols with 1.5 equiv of NiCl26H2O and 3.0 equiv of NaBH4 in methanol medium at 0 °C would be the ideal condition for the reaction. The optimized condition was generalized with various benzyl protected phenols, which afforded the products in excellent yields (Table 3, entries 1–9) within a reaction time of
5–10 min. While the scope of this procedure was successfully verified, the chemoselectivity observed was of greater interest. A distinct difference in reactivity was demonstrated by the alkyl and aryl benzyl ethers. The aryl ethers underwent reaction while the impervious alkyl ethers did not, providing selectivity. A similar fate was observed for allyl aryl ethers under the same reaction condition (Table 3, entries 10–18), which gave the corresponding phenols in 5–10 min. The procedure works well for aryl rings bearing both electron-donating and withdrawing groups and the position of the substituents on the aryl ring did not significantly deter the quantitative outcome of the reaction. It is to mention that the ester and nitrile groups would survive the reaction condition to witness the conversion of aryl ethers to phenols. A plausible mechanism for the reaction is illustrated in Figure 1. It is expected that nickel forms a chelated complex with the p-electrons of the aryl ring, which weakens the aryl-oxygen bond signif-
M. Chouhan et al. / Tetrahedron Letters 54 (2013) 4540–4543
icantly. This facilitates the donation of electrons from the oxygen atom to the electron deficient boron resulting in the attack of hydride on the benzylic/allylic carbon, and consequently the cleavage of the ether linkage. The high bonding affinity between oxygen and boron aided by the polar protic medium which stabilizes the partial charges of the transition state could be attributed to the faster reaction kinetics and chemoselectivity. The evidence for complexation is apparent from the inert nature of the alkyl ethers which did not cleave even with an excess amount of the reagents (Scheme 2). The lack of p-electrons does not materialize the necessity for complex formation with nickel. Thus the availability of the p-electrons of the aryl ring for complexation, and the coordination between oxygen and boron in the transition state assist the reactions of aryl ethers. The effect of coordination was also discernible from the reactions of benzyl/allyl amines which remained unreactive (Scheme 2), and hence chemoselective cleavage of the aryl ether was feasible in their presence. This could be rationalized by the fact that nitrogen forms a strong chelate complex with nickel, and therefore lacks coordination with boron to facilitate a hydride transfer to the allylic/benzylic carbon. The basic nature of the amine is also neutralized to a significant extent by the Lewis acid character of NiCl2. On the contrary, the oxygen of the aryl ethers is a better centre for coordination with boron. Though the in situ formation of nickel boride and its role in the reaction may be speculated, it was convincingly eliminated by an independent reaction. Addition of NaBH4 to a solution of NiCl26H2O in methanol generates a black precipitate of nickel boride with a vigorous effervescence. Introducing benzyloxybenzene to this reaction mixture did not afford phenol. This result indicates the possibility of nickel salt forming a chelated complex with the aryl ethers initially and thereafter the transfer of hydride occurs to cleave the CAO bond. To a certain extent, in situ formed nickel hydride can also be envisioned to be responsible for the deprotection.22a Though a few possibilities could be speculated for the mechanistic aspects of this reaction, the exact details need to be convincingly established. In summary, a highly efficient and economic strategy for chemoselective deprotection of aryl ethers was developed. The benzyl/allyl aryl ethers were selectively cleaved in the presence of their alkyl counterparts, using an inexpensive reagent combination of NiCl26H2O/NaBH4 in methanol at 0 °C within a short reaction time of 5–10 min. A variation in reactivity was observed with other functional groups. While the alkyl ethers remained inert, the ester and nitrile groups survive the reaction condition. The benzyl/allyl protected amines were also unreactive. The availability of the p-electrons of the aryl ring for complex formation with nickel, and the coordination between oxygen and boron have been reasoned for the observed reactivity and chemoselectivity.
4543
Acknowledgment Funding from the Department of Science and Technology, Government of India is gratefully acknowledged. Supplementary data Supplementary data (experimental procedures, compound data and scanned spectra (1H NMR, 13C NMR and HRMS)) associated with this article can be found, in the online version, at http:// dx.doi.org/10.1016/j.tetlet.2013.06.072. References and notes 1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John Wiley & Sons: New York, 1991; (b) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry Part B: Reactions and Synthesis, 5th ed.; Springer Science and Business Media, LLC, 2007. 2. (a) Bhatt, M. V.; Kulkarni, S. U. Synthesis 1983, 249; (b) Ranu, B. C.; Bhar, S. Org. Prep. Proced. Int. 1996, 28, 371; (c) Weissman, S. A.; Zewge, D. Tetrahedron 2005, 61, 7833. 3. Benton, F. L.; Dillon, T. E. J. Am. Chem. Soc. 1942, 64, 1128. 4. Feutrill, G. I.; Mirrington, R. N. Tetrahedron Lett. 1970, 11, 1327. 5. Jung, M. E.; Lyster, M. A. J. Org. Chem. 1977, 42, 3761. 6. Brooks, P. R.; Wirtz, M. C.; Vetelino, M. G.; Rescek, D. M.; Woodworth, G. F.; Morgan, B. P.; Coe, J. W. J. Org. Chem. 1999, 64, 9719. 7. Beyerman, H. C.; Heiszwolf, G. J. J. Chem. Soc. 1963, 755. 8. Ganem, B.; Small, V. R., Jr. J. Org. Chem. 1974, 39, 3728. 9. Yadav, J. S.; Chandrasekhar, S.; Sumithra, G.; Kache, R. Tetrahedron Lett. 1996, 37, 6603. 10. Thomas, R. M.; Mohan, G. H.; Iyengar, D. S. Tetrahedron Lett. 1997, 38, 4721. 11. Kamal, A.; Laxman, E.; Rao, N. V. Tetrahedron Lett. 1999, 40, 371. 12. Thomas, R. M.; Reddy, G. S.; Iyengar, D. S. Tetrahedron Lett. 1999, 40, 7293. 13. Boss, R.; Scheffold, R. Angew. Chem., Int. Ed. Engl. 1976, 15, 558. 14. Mereyala, H. B.; Guntha, S. Tetrahedron Lett. 1993, 34, 6929. 15. Taniguchi, T.; Ogasawara, K. Angew. Chem., Int. Ed. 1998, 37, 1136. 16. Hartung, W. H.; Simonoff, R. Org. React. 1953, 7, 263. 17. Mandal, P. K.; McMurray, J. S. J. Org. Chem. 2007, 72, 6599. 18. Pastore, A.; Valerio, S.; Adinolfi, M.; Iadonisi, A. Chem. Eur. J. 2011, 17, 5881. 19. Adinolfi, M.; Barone, G.; Guariniello, L.; Iadonisi, A. Tetrahedron Lett. 1999, 40, 8439. 20. Reist, E. J.; Bartuska, V. J.; Goodman, L. J. Org. Chem. 1964, 29, 3725. 21. Park, M. H.; Takeda, R.; Nakanishi, K. Tetrahedron Lett. 1987, 28, 3823. 22. (a) Sergeev, A. G.; Hartwig, J. F. Science 2011, 332, 439; (b) Tobisu, M.; Yamakawa, K.; Shimasaki, T.; Chatani, N. Chem. Commun. 2011, 2946; (c) Kelley, P.; Lin, S.; Edouard, G.; Day, M. W.; Agapie, T. J. Am. Chem. Soc. 2012, 134, 5480; (d) Sergeev, A. G.; Webb, J. D.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 20226; (e) Cornella, J.; Gómez-Bengoa, E.; Martin, R. J. Am. Chem. Soc. 2013, 135, 1997. 23. (a) Kumar, V.; Raghavaiah, P.; Mobin, S. M.; Nair, V. A. Org. Biomol. Chem. 2010, 8, 4960; (b) Kumar, V.; Nair, V. A. Tetrahedron Lett. 2010, 51, 966; (c) Khatik, G. L.; Khurana, R.; Kumar, V.; Nair, V. A. Synthesis 2011, 3123; (d) Kumar, V.; Khatik, G. L.; Nair, V. A. Synlett 2011, 2997; (e) Kumar, V.; Pal, A.; Khatik, G. L.; Nair, V. A Tetrahedron: Asymmetry 2012, 23, 434; (f) Khatik, G. L.; Kumar, V.; Nair, V. A. Org. Lett. 2012, 14, 2442; (g) Chouhan, M.; Sharma, R.; Nair, V. A. Org. Lett. 2012, 14, 5672; (h) Kumar, V.; Kumar, K.; Pal, A.; Khatik, G. L.; Nair, V. A. Tetrahedron 2013, 69, 1747.
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
NiCl26H2O/NaBH4 in methanol: a mild and efficient strategy for chemoselective deallylation/debenzylation of aryl ethers Mangilal Chouhan a, Kapil Kumar a, Ratnesh Sharma a, Vikas Grover b, Vipin A. Nair a,⇑ a b
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, Mohali, Punjab 160062, India Central Instrumentation Laboratory, National Institute of Pharmaceutical Education and Research, Sector 67, Mohali, Punjab 160062, India
a r t i c l e
i n f o
Article history: Received 2 May 2013 Revised 12 June 2013 Accepted 15 June 2013 Available online 24 June 2013
a b s t r a c t Deprotection of allyl/benzyl aryl ethers was achieved chemoselectively. The mild and inexpensive reagent combination of NiCl26H2O/NaBH4 in methanol afforded the products in high yields, within a reaction time of 5–10 min. Ó 2013 Elsevier Ltd. All rights reserved.
Keywords: Nickel chloride hexahydrate Sodium borohydride Debenzylation Deallylation Chemoselectivity
Selective protection and deprotection of functional groups is an art and challenge in the synthesis of complex organic molecules. Of the various kinds of protections available for alcohols/phenols,1,2 ethers are widely preferred owing to their stability towards nucleophiles and bases. A number of reagents are used to cleave primary alkyl aryl ethers such as BBr3,3 EtSNa/DMF,4 TMSI5 and BCl3/n-Bu4NI.6 Although simple alkyl groups serve as effective protecting groups, deprotection requires strongly electrophilic reagents/conditions. Because of their stability, t-butyl ethers are cleaved under moderately acidic conditions using either CF3COOH7 or FeCl3 in (CH3CO)2O.8 The allyl group, usually stable under basic and acidic conditions, is another widely used protecting group for alcohols and phenols. Methods for regeneration of alcohols from allylic ethers include DDQ,9 NaBH4/I2,10 Me3SiCl/NaI,11 CeCl37H2O/NaI12 or Pd/C/H2.13 Cleavage of allyl groups has been reported using PdCl2/CuCl/DMF–H2O/O214 or with DIBAL and catalytic NiCl2(dppp).15 The benzyl group can be used for the protection of the hydroxy groups when acidic conditions for ether cleavage are not tolerated. The benzyl protection is removed either by using Pd/C/H2,16 Pd/C/TES,17 I2/TES,18 NaBrO3/Na2S2O419 or with Na+ or K+ in NH3.20 Lewis acids21 such as FeCl3 and SnCl4 also afford alcohols from benzyl ethers. The cleavage of inert aryl ethers using different Ni salts is also reported.22 Though several methods are available for the deprotection of ethers, the limitations imposed by the substrates/reagents/procedures provide sufficient scope ⇑ Corresponding author. Tel.: +91 172 229 2045; fax: +91 172 221 4692. E-mail addresses: [email protected], [email protected] (V.A. Nair). 0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2013.06.072
Scheme 1. Debenzylation of aryl benzyl ether.
Table 1 Effect of metal saltsa
a
Entry
Metal salts (equiv)
NaBH4 (equiv)
Time (min)
Yield (%)
1 2 3 4 5 6 7 8 9 10
— NiCl26H2O (1.0) FeCl3 (1.0) CoCl26H2O (1.0) NiCl26H2O (1.0) PdCl2 (1.0) CuCl (1.0) NiCl26H2O (1.5) NiCl26H2O (1.5) NiCl26H2O (1.5)
1.0 — 1.0 1.0 1.0 1.0 1.0 2.0 3.0 4.0
30 30 30 30 15 30 30 15 5 5
— — 20 45 70 46 Trace 85 92 93
Benzyloxybenzene (1.0 equiv), methanol (5 mL).
for the development of newer methods. Based on our interests in reaction methodology23 we were in search of a suitable strategy for selective protection–deprotection of polyhydroxy compounds,
4541
M. Chouhan et al. / Tetrahedron Letters 54 (2013) 4540–4543 Table 2 Effect of solventsa
a
Entry
Solvent
Time (min)
Yield (%)
1 2 3 4 5 6 7
Toluene MeCN DMF THF Water EtOH MeOH
30 30 30 30 30 30 5
— — — — 20 50 92
Benzyloxybenzene (1.0 equiv), NiCl26H2O (1.5 equiv), NaBH4 (3.0 equiv).
taking advantage of the variations in reactivity/environment of the hydroxy groups. Our efforts culminated in a mild and efficient procedure for the deprotection of aryl benzyl ethers and allyl aryl ethers using NiCl26H2O and NaBH4 in methanol to afford phenols. The chemoselectivity is demonstrated by the indolent reagent nature towards alkyl ethers. The procedure utilizes reagents that does not require prior preparation and has advantages such as neither strongly basic nor acidic conditions are required, no precautions to exclude moisture or air from the reaction, inexpensive reagents and excellent yields in a short reaction time of 5–10 min.
Table 3 Reactions of allyl/benzyl ethers with NiCl26H2O/NaBH4a Entry
Substrate
Product
Yieldb (%)
1
92
2
93
3
90
4
92
5
88
6
89
7
90
8
90
9
90
10
89
11
90
12
90
13
90
14
87
15
93
16
88
(continued on next page)
4542
M. Chouhan et al. / Tetrahedron Letters 54 (2013) 4540–4543
Table 3 (continued) Entry
a b
Substrate
Product
Yieldb (%)
17
88
18
92
Substrate (1.0 equiv), NiCl26H2O (1.5 equiv), NaBH4 (3.0 equiv), methanol (5 mL). Isolated yield.
Figure 1. Plausible reaction mechanism.
Scheme 2. Chemoselectivity of the reaction.
A detailed investigation was performed on benzyloxybenzene by reacting it with sodium borohydride and different metal salts in methanol at 0 °C (Scheme 1). Salts of transition metals such as Fe, Co, Ni, Pd and Cu were evaluated (Table 1). NiCl26H2O provided maximum yields of phenol in 5 min, while other metal salts gave inferior yields. An examination of the effect of the solvents on the outcome of the reaction indicated that non-polar and polar aprotic solvents did not facilitate the reaction while polar protic solvents such as water and ethanol showed an improvement (Table 2). The best result was obtained with methanol. From the above results we concluded that reacting 1.0 equiv of the benzyl protected phenols with 1.5 equiv of NiCl26H2O and 3.0 equiv of NaBH4 in methanol medium at 0 °C would be the ideal condition for the reaction. The optimized condition was generalized with various benzyl protected phenols, which afforded the products in excellent yields (Table 3, entries 1–9) within a reaction time of
5–10 min. While the scope of this procedure was successfully verified, the chemoselectivity observed was of greater interest. A distinct difference in reactivity was demonstrated by the alkyl and aryl benzyl ethers. The aryl ethers underwent reaction while the impervious alkyl ethers did not, providing selectivity. A similar fate was observed for allyl aryl ethers under the same reaction condition (Table 3, entries 10–18), which gave the corresponding phenols in 5–10 min. The procedure works well for aryl rings bearing both electron-donating and withdrawing groups and the position of the substituents on the aryl ring did not significantly deter the quantitative outcome of the reaction. It is to mention that the ester and nitrile groups would survive the reaction condition to witness the conversion of aryl ethers to phenols. A plausible mechanism for the reaction is illustrated in Figure 1. It is expected that nickel forms a chelated complex with the p-electrons of the aryl ring, which weakens the aryl-oxygen bond signif-
M. Chouhan et al. / Tetrahedron Letters 54 (2013) 4540–4543
icantly. This facilitates the donation of electrons from the oxygen atom to the electron deficient boron resulting in the attack of hydride on the benzylic/allylic carbon, and consequently the cleavage of the ether linkage. The high bonding affinity between oxygen and boron aided by the polar protic medium which stabilizes the partial charges of the transition state could be attributed to the faster reaction kinetics and chemoselectivity. The evidence for complexation is apparent from the inert nature of the alkyl ethers which did not cleave even with an excess amount of the reagents (Scheme 2). The lack of p-electrons does not materialize the necessity for complex formation with nickel. Thus the availability of the p-electrons of the aryl ring for complexation, and the coordination between oxygen and boron in the transition state assist the reactions of aryl ethers. The effect of coordination was also discernible from the reactions of benzyl/allyl amines which remained unreactive (Scheme 2), and hence chemoselective cleavage of the aryl ether was feasible in their presence. This could be rationalized by the fact that nitrogen forms a strong chelate complex with nickel, and therefore lacks coordination with boron to facilitate a hydride transfer to the allylic/benzylic carbon. The basic nature of the amine is also neutralized to a significant extent by the Lewis acid character of NiCl2. On the contrary, the oxygen of the aryl ethers is a better centre for coordination with boron. Though the in situ formation of nickel boride and its role in the reaction may be speculated, it was convincingly eliminated by an independent reaction. Addition of NaBH4 to a solution of NiCl26H2O in methanol generates a black precipitate of nickel boride with a vigorous effervescence. Introducing benzyloxybenzene to this reaction mixture did not afford phenol. This result indicates the possibility of nickel salt forming a chelated complex with the aryl ethers initially and thereafter the transfer of hydride occurs to cleave the CAO bond. To a certain extent, in situ formed nickel hydride can also be envisioned to be responsible for the deprotection.22a Though a few possibilities could be speculated for the mechanistic aspects of this reaction, the exact details need to be convincingly established. In summary, a highly efficient and economic strategy for chemoselective deprotection of aryl ethers was developed. The benzyl/allyl aryl ethers were selectively cleaved in the presence of their alkyl counterparts, using an inexpensive reagent combination of NiCl26H2O/NaBH4 in methanol at 0 °C within a short reaction time of 5–10 min. A variation in reactivity was observed with other functional groups. While the alkyl ethers remained inert, the ester and nitrile groups survive the reaction condition. The benzyl/allyl protected amines were also unreactive. The availability of the p-electrons of the aryl ring for complex formation with nickel, and the coordination between oxygen and boron have been reasoned for the observed reactivity and chemoselectivity.
4543
Acknowledgment Funding from the Department of Science and Technology, Government of India is gratefully acknowledged. Supplementary data Supplementary data (experimental procedures, compound data and scanned spectra (1H NMR, 13C NMR and HRMS)) associated with this article can be found, in the online version, at http:// dx.doi.org/10.1016/j.tetlet.2013.06.072. References and notes 1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John Wiley & Sons: New York, 1991; (b) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry Part B: Reactions and Synthesis, 5th ed.; Springer Science and Business Media, LLC, 2007. 2. (a) Bhatt, M. V.; Kulkarni, S. U. Synthesis 1983, 249; (b) Ranu, B. C.; Bhar, S. Org. Prep. Proced. Int. 1996, 28, 371; (c) Weissman, S. A.; Zewge, D. Tetrahedron 2005, 61, 7833. 3. Benton, F. L.; Dillon, T. E. J. Am. Chem. Soc. 1942, 64, 1128. 4. Feutrill, G. I.; Mirrington, R. N. Tetrahedron Lett. 1970, 11, 1327. 5. Jung, M. E.; Lyster, M. A. J. Org. Chem. 1977, 42, 3761. 6. Brooks, P. R.; Wirtz, M. C.; Vetelino, M. G.; Rescek, D. M.; Woodworth, G. F.; Morgan, B. P.; Coe, J. W. J. Org. Chem. 1999, 64, 9719. 7. Beyerman, H. C.; Heiszwolf, G. J. J. Chem. Soc. 1963, 755. 8. Ganem, B.; Small, V. R., Jr. J. Org. Chem. 1974, 39, 3728. 9. Yadav, J. S.; Chandrasekhar, S.; Sumithra, G.; Kache, R. Tetrahedron Lett. 1996, 37, 6603. 10. Thomas, R. M.; Mohan, G. H.; Iyengar, D. S. Tetrahedron Lett. 1997, 38, 4721. 11. Kamal, A.; Laxman, E.; Rao, N. V. Tetrahedron Lett. 1999, 40, 371. 12. Thomas, R. M.; Reddy, G. S.; Iyengar, D. S. Tetrahedron Lett. 1999, 40, 7293. 13. Boss, R.; Scheffold, R. Angew. Chem., Int. Ed. Engl. 1976, 15, 558. 14. Mereyala, H. B.; Guntha, S. Tetrahedron Lett. 1993, 34, 6929. 15. Taniguchi, T.; Ogasawara, K. Angew. Chem., Int. Ed. 1998, 37, 1136. 16. Hartung, W. H.; Simonoff, R. Org. React. 1953, 7, 263. 17. Mandal, P. K.; McMurray, J. S. J. Org. Chem. 2007, 72, 6599. 18. Pastore, A.; Valerio, S.; Adinolfi, M.; Iadonisi, A. Chem. Eur. J. 2011, 17, 5881. 19. Adinolfi, M.; Barone, G.; Guariniello, L.; Iadonisi, A. Tetrahedron Lett. 1999, 40, 8439. 20. Reist, E. J.; Bartuska, V. J.; Goodman, L. J. Org. Chem. 1964, 29, 3725. 21. Park, M. H.; Takeda, R.; Nakanishi, K. Tetrahedron Lett. 1987, 28, 3823. 22. (a) Sergeev, A. G.; Hartwig, J. F. Science 2011, 332, 439; (b) Tobisu, M.; Yamakawa, K.; Shimasaki, T.; Chatani, N. Chem. Commun. 2011, 2946; (c) Kelley, P.; Lin, S.; Edouard, G.; Day, M. W.; Agapie, T. J. Am. Chem. Soc. 2012, 134, 5480; (d) Sergeev, A. G.; Webb, J. D.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 20226; (e) Cornella, J.; Gómez-Bengoa, E.; Martin, R. J. Am. Chem. Soc. 2013, 135, 1997. 23. (a) Kumar, V.; Raghavaiah, P.; Mobin, S. M.; Nair, V. A. Org. Biomol. Chem. 2010, 8, 4960; (b) Kumar, V.; Nair, V. A. Tetrahedron Lett. 2010, 51, 966; (c) Khatik, G. L.; Khurana, R.; Kumar, V.; Nair, V. A. Synthesis 2011, 3123; (d) Kumar, V.; Khatik, G. L.; Nair, V. A. Synlett 2011, 2997; (e) Kumar, V.; Pal, A.; Khatik, G. L.; Nair, V. A Tetrahedron: Asymmetry 2012, 23, 434; (f) Khatik, G. L.; Kumar, V.; Nair, V. A. Org. Lett. 2012, 14, 2442; (g) Chouhan, M.; Sharma, R.; Nair, V. A. Org. Lett. 2012, 14, 5672; (h) Kumar, V.; Kumar, K.; Pal, A.; Khatik, G. L.; Nair, V. A. Tetrahedron 2013, 69, 1747.