DHP-THP羟基保护与脱保护方法.pdf

Cupric sulfate pentahydrate (CuSO45H2O): a mild and effi cient catalyst for tetrahydropyranylation/ depyranylation of alcohols and phenols Abu T. Khan,*Lokman H. Choudhury and Subrata Ghosh Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India Received 22 July 2004; revised 15 August 2004; accepted 24 August 2004 Available online 11 September 2004 This paper is dedicated to Professor H. Ila on the occasion of her 60th birthday AbstractVarious alcohols and phenols can be smoothly converted to the corresponding THP ethers using 20mol% CuSO45H2O under mild reaction conditions at room temperature. Some of the major advantages of this procedure are nonaqueous work-up, very good yields, less expensive catalyst and compatibility with other protecting groups. ? 2004 Elsevier Ltd. All rights reserved. The tetrahydropyranyl (THP) group is frequently used for the protection of alcohols and phenols due to their ease of preparation and stability under a wide variety of reaction conditions such as with hydrides, alkylating reagents,Grignardreagentsandorganometallic reagents.1In addition, they also serve as stable protect- ing group in peptide, nucleoside and nucleotide, carbo- hydrate and steroid chemistry. Tetrahydropyranylation of alcohols can be accomplished by using p-TSA,2 BF3OEt23and PPTS.4Some of the recently used reagents that can catalyze both tetrahydropyranylation and depyranylation are ZrCl4,5I2,6LiBr,7acetonyltri- phenylphosphoniumbromide(ATPB),8TBATB,9 aluminiumchloridehexahydrate,10In(OTf)3,11 dialkylimidazoliumtetrachloroaluminates,12InCl3 immobilized in ionic liquids13and bromodimethylsulfo- nium bromide.14On the other hand, many methods have also been developed by using heterogeneous cata- lysts, and these have been reviewed recently.15However, some of these procedures have some diffi culties such as requirement of much longer reaction times, incompati- bility with other acid-sensitive functional groups,3,9,10,13 involvement of expensive and moisture sensitive cata- lysts and some of them have to be prepared prior to use.4,8,9,14There is a need for a greener catalytically effi cient method, which might work under mild and economically cheaper conditions. As a part of our ongoing research program to develop new synthetic methodologies involving various new reagents,16,17we perceived that cupric sulfate pentahydrate, which is readily available, might be a useful catalyst for tetra- hydropyranylation because of its mild Lewis acidity. In this paper we disclose that cupric sulfate pentahy- drate can be used as an effi cient catalyst for tetrahydro- pyranylation/depyranylation of alcohols and phenols as shown in Scheme 1. When a mixture of 1-hexadecanol 1a and 3,4-dihydro- 2H-pyran was treated with 20mol% of cupric sulfate pentahydrate in acetonitrile as solvent, it was smoothly converted to the corresponding THP ether 2a within 0040-4039/$ - see front matter ? 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2004.08.141 Keyword: Protection of hydroxyl compounds. *Corresponding author. Tel.: +91 361 2582305; fax: +91 361 2690762; e-mail: atk CuSO4. 5H2O CH3CN / rt / 40 min-12 h O O R ROH 1 2 O + CuSO4. 5H2O CH3OH OCH3O / rt / 2-6 h Scheme 1. R = alkyl/aryl/sugar residue/nucleoside residue. Tetrahedron Letters 45 (2004) 78917894 Tetrahedron Letters 40min in 90% yield. Similarly, 4-methoxybenzyl alcohol 1b was converted to the corresponding THP ether 2b within40minunderidenticalreactionconditions. Althoughdichloromethanecanalsobeused,we employed acetonitrile as solvent because dichlorometh- ane is a halogenated solvent and harmful. The tetra- hydropyranylation could be achieved on a large scale between 10 and 100mmol without any diffi culty. Fol- lowing the typical reaction procedure,18various benz- ylic, allylic and secondary alcohols 1ci as well as phenols 1jk were smoothly transformed to the corre- sponding THP ethers 2ck, respectively, in very good yields. Remarkably, various diols were transformed to mono THP ethers 2ln along with 58% di-THP ether by using 20mol% catalyst instead of 40mol% catalyst. The diols could be converted to the di-THP ethers 2op in good yields in a similar manner. In various sub- strates containing other functional groups such as acetyl, TBDMS and TBDPS ethers, isopropylidene protected diols and benzyl ethers were smoothly con- verted to the desired THP ethers 2qw in good yields as shown in Table 1. All the products were fully Table 1. Tetrahydropyranylation of alcohols and phenols in presence of a catalytic amount of CuSO45H2O EntrySubstrate 1Time (min)Product 2aYieldb(%) a OH n n = 13 40 n OTHP n = 13 90 b OH MeO40MeO OTHP 89 c OH 40 OTHP 91 dCl OH 45 OTHP Cl 92 e O OH 40 O OTHP 90 f OH 55 OTHP 87 g OH 60 THPO 89 h OH 55 OTHP 91 i C8H17 OH 80 C8H17 THPO 85 j OHCl95ClOTHP87 kOH MeO 90OTHP MeO 89 l OHOH 45 THPOOH 70 m OHOHn n = 4 12 h OHOTHPn n = 4 83c n OH OH 60 OTHP OH 55 o OH OH 90 OTHP THPO 92 p OHOHn n = 4 12 h THPOOTHPn n = 4 93 qOHOAc40THPOOAc84 r OHOTBDMS40 THPOOTBDMS82 sOHOTBDPS40THPO OTBDPS82 7892A. T. Khan et al. / Tetrahedron Letters 45 (2004) 78917894 characterized by IR, 1H NMR spectroscopy and by ele- mental analyses. The most interesting feature is that the THP ether 2a undergoes cleavage within 5h using same catalyst (20mol%) in methanol in 85% yield.19Other THP ethers 2b, 2c, 2f and 2k were converted to the respective hydroxyl compounds 1b, 1c, 1f and 1k within 26hin8085%yieldsunderidenticalreaction conditions. The tetrahydropyranylation of 4-methoxybenzyl alcohol 1b was investigated with the various forms of cupric sul- fate to fi nd out the relative effi ciencies (Table 2). Cupric sulfate pentahydrate showed the highest catalytic activ- ity in terms of reaction time and yield. In summary, the present methodology demonstrates Cu- SO45H2 O as an eff ective catalyst for tetrahydropyranyl- ation/depyranylation of alcohols and phenols. The main advantages of our protocol are: mild, clean, environ- mentally benign reaction conditions as well as good yields. In addition, our methodology might be useful for the substrates containing acid-sensitive protecting groups because of the almost neutral reaction condi- tions. Furthermore, this method is also expected to have better applicability in organic synthesis due to the low cost of the reagent. We believe this protocol will beausefuladditiontothemodernsynthetic methodologies. Acknowledgements A.T.K. thanks the DST, New Delhi for a fi nancial grant (Grant No SP/S1/G-35/98), L.H.C. and S.G. are grateful to IITG for their research fellowships. The authors are also grateful to the referee for his valuable comments and suggestions. References and notes 1. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John Wiley p 49. 2. (a) Corey, E. J.; Niwa, H.; Knolle, J. J. Am. Chem. Soc. 1978, 100, 1942; (b) Bernady, K. F.; Floyd, M. B.; Poletto, J. F.; Weiss, M. J. J. Org. Chem. 1979, 44, 1438. 3. Alper, H.; Dinkes, L. Synthesis 1972, 81. 4. Miyashita, M.; Yoshikoshi, A.; Grieco, P. A. J. Org. Chem. 1977, 42, 3772. 5. Rezai, N.; Meybodi, F. A.; Salehi, P. Synth. Commun. 2000, 30, 1799. 6. Deka, N.; Sarma, J. C. Synth. Commun. 2000, 30, 4435. 7. Reddy, M. A.; Reddy, L. R.; Bhanumathi, N.; Rao, K. R. Synth. Commun. 2000, 30, 4323. 8. Hon, Y.-S.; Lee, C.-F. Tetrahedron Lett. 1999, 40, 2389. 9. Naik, S.; Gopinath, R.; Patel, B. K. Tetrahedron Lett. 2001, 42, 7679. 10. Namboodiri, V. V.; Varma, R. S. Tetrahedron Lett. 2002, 43, 1143. 11. Mineno, T. Tetrahedron Lett. 2002, 43, 7975. 12. Namboodiri, V. V.; Verma, R. S. Chem. Commun. 2002, 342. 13. Yadav, J. S.; Subba Reddy, B. V.; Gnaneshwar, D. New J. Chem. 2003, 202. 14. Khan, A. T.; Mondal, E.; Borah, B. M.; Ghosh, S. Eur. J. Org. Chem. 2003, 4113. 15. Sartori, G.; Ballini, R.; Bigi, F.; Bosica, G.; Maggi, R.; Righi, P. Chem. Rev. 2004, 104, 199. 16. Khan, A. T.; Mondal, E.; Ghosh, S.; Islam, S. Eur. J. Org. Chem. 2004, 22, 2002. Table 1 (continued) EntrySubstrate 1Time (min)Product 2aYieldb(%) t OH O O 50 OTHP O O 85 u O O O O O OH 85 O O O O O OTHP 83 v O BnOBnO OBn OH OMe 90 O BnOBnO OBn THPO OMe 81 w O OH N N O O OO 45 O THPO N N O O OO 90 aAll products were characterized by IR,1H NMR and elemental analysis. bIsolated yields. cYield based on starting material recovery. Table 2. Tetrahydropyranylation of 4-methoxybenzyl alcohol 1b using various forms of cupric sulfatea RunCatalystConversion (%)Time (min/h) 1CuSO45H2O10045 2CuSO4803 3CuSO4SiO2902.5 4SiO203 aReactions were monitored by GC. A. T. Khan et al. / Tetrahedron Letters 45 (2004) 789178947893 17. Khan, A. T.; Ghosh, S.; Choudhury, L. H. Eur. J. Org. Chem. 2004, 2198. 18. Typical procedure of protection: Into a mixture of 3,4- dihydro-2H-pyran (1.1mmol) and alcohol or phenol (1mmol) in acetonitrile (2mL) was added cupric sulfate pentahydrate (0.05g, 0.2mmol) at room temperature and the mixture stirred until completion of the reaction was ascertained by the disappearance of the alcohol spot on TLC. The product was isolated in almost pure form from the reaction mixture by simply fi ltering through a What- man 42 fi lter paper without aqueous work-up