磺酸酯还原文献

Me0 \
6OMe
OH
Scheme I
Me0
'
OH
OMe
Me0 \
R
OMe
R= H, Alky1,Alkenyl
Alkinyl, Carboxyl Formyl, etc
recent publication^?^ each one of them claiming the usefulness of the cleavage reagent employed. For the most part these reactions belong to the three following types: (a) hydrogenolysis under heterogeneous conditions (Pd/C, Ni Raney); (b) Pd(0)-catalyzed reduction under homogeneous conditions; (c) reduction induced by alkali (Na, K, Li) or other zero-valent (Ti) metals. In spite of these recent developments and of the tremendous activity witnessed in the field of palladiumcatalyzed C-H (and C-C) bond formation while this work was still in p r o g r e s ~ , ~ ~ ~our belief that the reported it is J ~ methodology is not useful for the highly encumbered and functionalized substrates required in our objectives6 (vide infra). Actually, most papers either deal with unhindered phenol derivatives or describe reduction problems when sterically hindered ones are used. Only zerovalent metal reductions, as expected, are effective for the reduction of phenol derivatives when severe steric hindrance exists.'
Due to the synthetic importance of having appropriate methodology for the conversion of shikimic acid metabolites into polyketide metabolites,' we planned to demonstrate the versatility of the following conceptually simple design (Scheme I). The first part of the plan was based in our recent work on the direct lithiation of phenols, which allowed us to introduce, with great ease, a variety of electrophiles (E, and E2 in Scheme I) onto highly substituted phenoh2 As an added bonus, the symmetric nature of the starting material required for our purposes (4-hydroxy-3,5-dimethoxybenzyl methyl ether) clearly simplified the regioselectivity problems foreseen in the metalation step of nonsymmetric phenols. On the other hand, the second part of the plan called for developing appropriate conditions for the removal of the phenolic group in highly hindered electron-rich substrates and the simultaneous introduction of different groups such as hydrogen, alkyl, alkenyl, alkynyl, carbaldehyde, carboxyl, et^.^ This, we expected, would provide derivatives of potential interest as advanced intermediates for the synthesis of complex polyketide metabolites. According to the currently accepted mechanism for these and related serious problems were expected as a consequence of the strong (negative) influence of both steric hindrance and (the presence of) electron-donating substituents on the reaction rate of the oxidative addition4b and reductive e l i m i n a t i ~ n ~ ~ steps. The deoxygenation of hindered phenols, the matter of the present report, was planned the first target, the remaining objectives being allocated for future development. Actually, the deoxygenation (COH CH) of a variety of phenol derivatives such as esters, ethers, urethanes, ureas, etc., has been the target issue of an abundant number of
(5) Methoden der Organischen Chemie (Houben Weyl),Band 6/lc, Teil 2; Georg Thieme Verlag: Stuttgart, 1976. (6) To our knowledge, very few hindered phenols (2,6-dimethylphenol and some 1-naphthol derivatives) have been the subject of Pd(0)-catalyzed deoxygenation studies. See ref 3, 15, and Chen, Q. Y.; He, Y.-B.; Chem. Commun. 1986,1452. C-C bond forYang, 2.-Y. J. Chem. SOC., mation has been achieved in hindered bromoaniline derivatives. See: Krolski, M. E.; Renaldo, A. F.; Rudisill, D. E.; Stille, J. K. J. Org. Chem. 1988,53,1170. (7) Welch, S. C.; Walters, M. E. J. Org. Chem. 1978,43,4797. See also ref 8 and 12. (8) For deoxygenation procedures leading to simple resorcinol dimethyl ethers, see: Bailey, K. Can. J.Chem. 1974,52,2136. Azzena, u.; Denurra, T.; Melloni, G.; Rassu, G. J.Chem. SOC., Chem. Commun. 1987, 1549. (9) Stang, P. J.; Hanack, M.; Subramanian, L. R. Synthesis 1982,85. (10) Care must be taken to ensure that no sulfur impurities accompany the desired triflates, as they apparently poisson the catalyst, thus precluding the reaction to take place. Typically, crude triflates (>95% pure by." NMR) need to be chromatographed (silicagel, methylene choride) prior to be submitted to Pd/C-catalyzed hydrogenolysis. (11) Phenol phosphates were prepared as described by Rossi, R. A.; Bunnett, J. F. J. Org. Chem. 1973, 38, 2314. (12) Dominianni, S. J.; Ryan, C. W.; DeArmitt, C. W. J. Org. Chem. 1977,42, 344. See also ref 11. (13) Cachi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1986,27, 5541. (14) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.; Hirotsu, K. J. Am. Chem. SOC. 1984,106, 158. (15)Peterson, G. A.; Kunnung, F. A.; McCallum, J. S.; Wulff, W. D. Tetrahedron Lett. 1987,28, 1381.