Z’etmhedron Vol. 50. No. 45, pp. 12999-13022, 1994 Copyright 0 1994 Elscviel science Ltd Printed in Great Britain. All rights cemwd 0040-4020194 $7.00+0.00 0040-4020(94)00824-8 Regiochemical Control of the Ring Opening of 1,2-Epoxides by Means of Chelating Processes. 8. Synthesis and Ring Opening Reactions of cis- and trans- Oxides Derived from 3-Benzyloxycyclohexene and 2-Benzyloxy-5,6-dihydro-2H-pyranl Federico Calvani, Paolo Crotti,+ Cristina Gardelli, and Mauro Pineschi Dipartimem~ di Chimica Bioorganica, UnivezsitA di Piss, Vii Booatmo 33.56126 Piss, Italy Dedicated to Prof. G Berti on the occasion zyxwvutsrqponmlkjihgfedcbaZYXWVUTS of his 70th birtha@ Abstract : The rqiocbemical outcome of the ring opening of 1,Zepoxides bearing polar remote functionalizacion through chelation processes assiaed by metal ions, was vcxified in cyclic oximne systems having the polar fo&onality in an allylic position to the oxiraoe ring. The dktewaisomeric cis&ans epoxide pairs $6 and 7,g derived from 3-benzyloxycyclohexene, and 2-benzyloxy-5,6- dihydm-W-pyran, respectively, were pqwcd and several of their opening reactions were studied The regiosekctivity observed largely depends on the reaction conditions (standard oi metal-assisted) and, interestingly, on the nature of the nockophile used. 1,2-Epoxides constitute one of the most important functional groups in organic chemistry: their easy availability and their ability to react with a large variety of nucleophiles (C, 0, and N-nucleophiles, halogenide, hydride, etc) make 1,2-epoxides a valuable tool in organic synthesis for the construction of two adjacent stereocenter%, once the regiochemistry of the opening process can be effectively driven.:! In fact, whereas the opening process of typically aliphatic and cycloaliphatic 1,2-epoxides is completely anti stereoselective? the regiochemistry observed in non-symmetrical systems can unfortunately be highly random. As a consequence, large efforts have been made in the last few years in order to devise reaction conditions and new methodologies able to carry out the opening process of 1,Zepoxides with nucleophiles under a rigid stereocontrol. Our previous ttsults in this field had shown that the presence of a protected heterofunctionality (OBn) in a homoallylic or homologous position with respect to the oxirane ring, in a cycloaliphatic system, was able to modify the regiochemical outcome of the opening process, depending on the operating conditions. L4 The best results were obtained with the cis epoxide 1, in which the OBn functionality is directly linked to the cyclohexane ring in a homoallylic relation to the oxirane systemp In the reaction of 1 with nucleophiles, the regioselecdvity turned out to be closely linked to the type of catalysis and to the presence of metallic species in the reaction medium to the point that a nice regioaltemating process was found, which was attributed to the incursion of chelated species of type 69 (Scheme 3)P We also found that a polar group inserted into a cyclic system, as in the tetrahydropyranil epoxide 2, can effectively intervene in directing the epoxide ring opening by means of chelating processes assisted by metal ions. 5 These studies are now extended to the 12999