Asymmetric rearrangement of N-Boc 7-azanorbornene oxide: use of aryllithiums for enantioselective deprotonation

Studies on organolithium-induced alkylative desymmetrisation of epoxides: synthesis of enantioenriched β-amino cycloheptenols from 6,7-epoxy-8-azabicyclo[3.2.1]octanes

“…These results are in accordance with previous observations that 1:1 RLi/bisoxazoline systems tend to favour transannular C -H insertion of lithiated epoxides over reductive alkylation. 11,20 As anticipated on the basis of previous studies, bisoxazoline 11 was found to favour the opposite enantiomers of 21 and 22 compared with sparteine 10. 3 We had previously observed with 3,4-epoxytetrahydrofuran that decreasing the quantity of chiral ligand relative to organolithium gave improved yields and ee of the resulting alkene diol (cf.…”

“…1). Ethers 7, 8 and 9 were anticipated to provide insight into steric (and any stereoelectronic) effects on product profile/ee, with the dimethylsubstituted system 9 additionally providing a 'block' against potentially competing transannular C -H insertion (cyclopropane formation) 11 from the a-lithiated epoxide (vide infra). Previous organolithium-induced reactions of epoxides 3 suggested that TBDMS and Boc protection should be compatible with the chemistry we intended to investigate.…”

“…10 This led to the desired amino cycloheptenols 21 (R¼Bu n , Pr i ) in poor yields (31% and 12%, respectively), together with azatricyclic alcohol 22 (19 and 23%, respectively) (Scheme 6, Table 1, entries 1 and 5); the latter likely arising from transannular C -H insertion of the intermediate a-lithiated epoxide. 3,11 Reaction of epoxide 7 under the typical conditions, but using preformed organolithium/sparteine complex, gave an improvement in the relative ratio of amino cycloheptenol 21: azatricyclic alcohol 22 compared to the ligand-free reactions [from 1.6:1 to 3.6:1 (for R¼Bu n ) and from 0.5:1 to 1:1 (for R¼Pr i ), Table 1, entries 2 and 6]. This led to isolation of the amino cycloheptenols 21 in improved yields, and significant asymmetric induction was also observed [58 and 72% ee (R¼Bu n ), 39 and 82% ee (R¼Pr i )].…”

“…The effect of reducing the amount of bisoxazoline 11 on the product profile in the reaction of epoxide 7 with Pr i Li was also investigated ( Table 2, entries [10][11][12]. It was found that using only 1 equiv.…”

Expanding the Utility of Lithiated Epoxides and Aziridines in Synthesis

“…26 To develop this synthetic route into an asymmetric one, the rearrangement of meso-epoxide 19 to azanortricyclanol 20 with a variety of enantiopure bases was examined. 29 However, the use of (S,S)-bis(1-phenyl)ethylamide as base led to 20 in low yield (20%) and ee (9%). A contributing factor to the low ee could be carbamate rotamers compromising the desymmetrisation.…”