General Papers ARKIVOC 2008 (ii) 160-171
To extend the generality and selectivity of Fe(O2CCF3)3 catalyzed aminolytic epoxide opening further, we allowed various epoxides to react with aniline (2a) in the presence of 1 mol% of Fe(O2CCF3)3 (Table 3). The treatment of cyclopentene oxide (7) with an equimolar amount of aniline (2a) at room temperature for 3 h in the presence of 1 mol% of Fe(O2CCF3)3 gave trans-2-(phenylamino)cyclopentanol (rac-8) in good yield (79% y; Table 3, entry 1). The reaction of epichlorohydrin (rac-9) with aniline (2a) at room temperature for 1 h in the presence of 1 mol% of Fe(O2CCF3)3 afforded the amino alcohol rac-10 as the sole regioisomer formed by the nucleophilic attack of aniline (2a) at the less hindered carbon atom of the epoxide ring (82% y; entry 2). The reaction of phenoxymethyl oxirane (rac-11) with aniline (2a) in turn furnished the corresponding amino alcohol rac-12 as only one regioisomeric product in good yield (78% y; entry 3). While the reaction of epichlorohydrin (rac-9) and phenoxymethyl oxirane (rac-11) gave the corresponding amino alcohols rac-10 and rac-12 in good yields under full-regioselectivity, in the reaction between 1-hexene oxide (rac-13) and aniline (2a) a moderate yield (58% y) and somewhat diminished regioselectivity (rac-14/rac-15 = 84:16; entry 4) were observed. It was also observed that the reaction between rac-13 and 2a was rather exothermic and 2a was not fully consumed at the end of the reaction (TLC). Additionally, another (side) product was observed on the TLC plate which was then isolated by column chromatography. The isolated side product (one spot on the TLC plate) was a mixture of two dimerization products formed from the reaction of two equivalents of 1-hexene oxide (rac-13) and one equivalent of aniline (2a) (GCMS, NMR). We isolated the mixture of the side products in a 25% yield. According to the NMR and GC spectra of the side products, the dimerization of 1-hexene oxide (rac-13) with aniline (2a) catalyzed by Fe(O2CCF3)3 proceeded via the ring opening of the second 1-hexene oxide molecule (rac-13) by the nucleophilic attack of the oxygen atom of the amino alcohols rac-14 and rac-15, and not the nitrogen atom.
In order to elucidate the stereospecificity of the Fe(O2CCF3)3 catalyzed aminolytic epoxide opening, the reaction of enantiomerically pure (R)-styrene oxide (4, >99% ee) with p-anisidine (2b) was performed (Scheme 1). We are pleased to report that the corresponding amino
alcohol 5b was obtained in enantiopure form in high yield and under high regioselectivity from enantiopure (R)-styrene oxide (4) and p-anisidine (2b) in the presence of 1 mol% of Fe(O2CCF3)3 (93% y, 5b/6b = 98:02, >99% ee for 5b). To the best of our knowledge, this is the first report on the synthesis of 5b in enantiopure form.9 Since enantiomerically pure epoxides are currently available by the hydrolytic kinetic resolution (HKR) of epoxides, this method could be rather useful for the synthesis of enantiopure 1,2-amino alcohols from enantiopure epoxides and amines.10
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