Benzylic epoxides

Sanchez, A. J. Konopelski, J. P. Phenol benzylic epoxide to quinone methide electron reorganization synthesis of ( )-taxodone. J. Org. Chem. 1994, 59, 5445-5452. 

This week s Highlights focuses on three transition metal-catalyzed reactions. Jin-Quan Yu of Cambridge University reports (Organic Lett. 2003,5,4665-4668) that Pd nanoparticles catalyze the hydrogenolysis of benzylic epoxides. The reaction proceeds with inversion of absolute configuration (1 —> 2). 

Styrene oxide undergoes attack at the benzylic epoxide carbon Atom exclusively (Eq. 001), giving 2-ozido-2-phenyle6hanol as sole product.1 70- 17 ... 

Benzylic epoxides that undergo rate-limiting 1,2-hydrogen migration 280 Benzo[a]pyrene 7,8-diol 9,10-epoxides 281 Summary of pH-independent mechanisms 283... 

Epoxide isomerization accompanying pH-independent reactions 283 10 Benzylic epoxides that exhibit complicated pH-rate profiles 286... 

BENZYLIC EPOXIDES THAT UNDERGO RATE-LIMITING 1,2-HYDROGEN MIGRATION... 

The observations that the pH-independent reactions of deuterium-labeled 5-met-hoxyindene oxide and 6-methoxy-1,2,3,4-tetrahydronaphthalene-1,2-oxide show significant primary kinetic deuterium isotope effects for the ketone-forming reactions, whereas the pH-independent reactions of deuterium-labeled naphthalene oxide and benzene oxide do not, are quite puzzling. Clearly, more work needs to be done to fully understand why transition-state structures for rearrangement of arene oxides to phenols differ from those for rearrangement of benzylic epoxides to ketones. 

Benzylic epoxides that exhibit complicated pH-rate profiles... 

A more complicated pH-rate profile is also observed for the hydrolysis reactions of benzo[a]pyrene diol epoxide epoxide 80, and is shown in Fig. 5.102 This profile shows Regions A-D that are similar to those for reaction of precocene I oxide 76 (Fig. 4), except that Region B reaches a full plateau that extends from pH 5 to 9 in water. The interpretation of this pH-rate profile is essentially the same as the interpretation of the profile for hydrolysis of precocene I oxide (Fig. 4). The pH-independent reaction of 80 in Region B (discussed in detail in Section Benzylic epoxides and arene oxides ) yields 60% tetrols in a stepwise mechanism involving a carbocation intermediate and 40% ketone from a completely separate pathway (Scheme 31). The negative inflection of the profile at pH 10-11.5 indicates that hydroxide ion reacts as a base with the intermediate carbocation to reform diol epoxide 80 and thus slow the reaction rate. There is a corresponding increase in the yield of ketone 107 at pH >11. 

General acid catalysis in the hydrolysis of 81 is quite facile. This reaction, as discussed in Section Benzylic epoxides and arene oxides and shown in Scheme 39, involves proton transfer to the epoxide oxygen concerted with epoxide C-O bond breaking to form a carbocation 83. For primary ammonium ions with pKa < 8, only the acid form of the amine is reactive, and carbocation formation is irreversible,... 

While allyl and glycidyl ethers are converted into a mixture of oxetane and oxepine products with xec-butyllithium, Mordini and co-workers reported that allyl, benzyl, and propargyl epoxy ethers can be regioselectively converted into 2-vinyl, 2-phenyl, or 2-aIkynyl-3-(hydroxyalkyl) oxetanes upon treatment with either Schlosser s base or other mixed metal bases. Some of the best results were obtained with the LDA/potassium ferf-butoxide mixture (LIDAKOR, ref 194). While rearrangement of propargylic or benzylic epoxide ethers formed exclusively the four-membered oxetanes, rearrangements of allyl oxiranyl ethers show a selectivity for cyclization to the seven-membered ring. Trialkylsilyl-substituted epoxide allyl ethers also show a preference for the oxepine, and mixtures are obtained as the size of the silyl substituents is increased (Scheme 17). 

The peroxy intermediate (1) is an excellent reagent for the synthesis of acid-sensitive benzylic epoxides from alkenes, the oxidation of benzylic CH2 to C=0, and the chemoselective oxidation of alkene sulfoxides to alkene sulfones. It is noteworthy that the reactions are carried out under mild conditions (—35 °C). 

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