Organolithium-Induced Synthesis of Unsaturated Diols from Epoxides of Dihydrofurans and Dihydropyrans

Abstract

Dihydrofuran and dihydropyran epoxides undergo a stereospecific alkylative double ring-opening with organolithiums to provide a new route to substituted alkenediols.Epoxides are versatile synthetic intermediates. 2 Their reactions are dominated by cleavage of the strained threemembered ring by nucleophilic opening and acid-or baseinduced isomerization reactions. The alkylative deoxygenation of epoxides 1 using organolithiums to give substituted alkenes 2 (Scheme 1) was originally discovered by Crandall and Lin, 3 and a number of research groups have subsequently made contributions to this area. 4 Scheme 1In one development of this methodology, Mioskowski and co-workers in 1996 reported that the reaction of organolithiums with cyclopentene-and cyclohexene-derived epoxides possessing a b-methoxy substituent results in the elimination of methoxide and formation of substituted cyclic allylic alcohols (e.g. Scheme 2). 5 Scheme 2Arising out of these previous observations, and in connection with our studies concerning the reactions of organolithiums with cycloalkene-and heterocycloalkenederived epoxides, 6 we speculated whether the chemistry exemplified in Scheme 2 could be extended to elimination from a cyclic ether 3 (Scheme 3). Both ethereal oxygens would be retained as hydroxyl groups in the product, and the overall process would represent a new strategy to substituted alkenediols 4. 7 Scheme 3We chose readily available 3,4-epoxytetrahydrofuran 5 as a substrate to test our hypothesis. 8 Reaction of 5 with BuLi (2.5 equiv.) in THF at -78°C cleanly gave 3-methyleneheptane-1,2-diol 7 in excellent yield (90%, Scheme 4). 7 As in Mioskowski's work (Scheme 2), the current reaction proceeds via ether cleavage rather than loss of Li 2 O; 5 this is despite b-elimination from the presumed lithiated intermediate 6 (Scheme 4) being the reverse of a stereoelectronically disfavoured 5-endo-trig cyclization. 9

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

“…Our studies began (Scheme 3) by reaction of BuLi (4 equiv) with a mixture of stannane 4 [6] (2 equiv) and tetramethylpiperidine (TMP, 2 equiv), to generate methoxymethyllithium and LTMP, followed by addition of terminal epoxide 5. This led to the desired allylic alcohol 6 (38%), likely via the selective (ring strain-relieving) 1,2-metalate rearrangement outlined in Scheme 2 (2→3, X = O, LG = OMe), then preferential β-elimination [7,8] of lithium methoxide rather than dilithium oxide. However, also isolated was dodecanal (50%), which arises from hydrolysis during work-up of the enamine that is formed from trapping of the lithiated epoxide by LTMP [9,10].…”

Aziridinyl Anions: Generation, Reactivity, and Use in Modern Synthetic Chemistry

“…Such a reductive alkylation process is well documented for lithiated oxiranes, which behave as electrophiles under particular reaction conditions. This electrophilic behavior is likely responsible for the TsNH 2 formation according to the mechanism reported in Scheme .…”

Recent Developments in the Chemistry of Lithiated Epoxides

“…When the above chemistry is applied to epoxides of unsaturated cyclic ethers 87, it results in substituted alkenediols 88. 56,57 This latter reaction proceeds with a wide array of organolithiums: primary, secondary or tertiary alkyl, as well as phenyl-and trimethylsilyllithium, the latter leading to an allylsilane (Scheme 31).…”