Untitled

Abstract

Enantioselektive Erzeugung und intermolekulares Abfangen eines Lithiumcarbenoids erfolgt bei der Reaktion von Epoxiden aus 2,5‐Dihydrofuran, 2,5‐Dihydropyrrol sowie Oxa‐ und Aza‐bicyclo[n.2.1]alkenen (n=2, 3) mit Organolithiumverbindungen in Gegenwart externer chiraler Liganden. Diese Methode kann zur Synthese wichtiger ungesättigter Diole und Aminoalkohole verwendet werden (siehe Schema; NBoc=N‐t‐Butoxycarbonyl).

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

“…) at 278 8C in Et 2 O, followed after 5 h by slow warming to 25 8C over 16 h]. 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].…”

“…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.…”

“…Repeated recrystallisation from light petroleum/EtOAc (9:1) gave colourless crystals; R f 0.13 (light petroleum/EtOAc 9:1); mp 86 -87 8C; n max (KBr)/cm 21 2978s, 2934m, 1713s, 1653s, 1456w, 1434w, 1367m, 1367m, 1327m, 1291m, 1211w and 1147s; d H (400 MHz) (two rotamers) 6.20 -6. 10 3 mmol) in toluene (50 mL) was cooled to 288 8C and DIBAL-H (1 mol dm 23 in toluene; 3.8 mL, 3.8 mmol) was added dropwise. The reaction mixture was allowed to warm up to 240 8C over 17 h, then diluted with Et 2 O (20 mL) and washed with a saturated solution of sodium potassium tartrate (15 mL).…”

“…10 Here we present in detail our studies on the desymmetrisation of epoxides of 8-azabicyclo [3.2.1]octenes. Our aim was to investigate whether it is possible to obtain enantioenriched b-amino cycloheptenols 6 (Scheme 3) from 6,7-epoxy-8-azabicyclo- [3.2.1]octanes 5 by reaction with different organolithiums in the presence of an external chiral ligand.…”

Enantioselective alkylative double ring-opening of epoxides derived from cyclic allylic ethers: synthesis of enantioenriched unsaturated diolsElectronic supplementary information (ESI) available: the preparation and characterisation of derivatives for ee determinations. See http://www.rsc.org/suppdata/ob/b2/b212404a/

“…In conjunction with our studies into the enantioselective deprotonations of cycloalkene-and heterocycloalkene-derived epoxides 5-8 we sought to develop the above alkylative desymmetrisation reaction of epoxides into an enantioselective entry to acyclic and cyclic unsaturated diols. 12 For such an asymmetric process using an organolithium with an external chiral (enantio-enriched or -pure) ligand, it seems probable that any enantioselectivity would originate from the initial discrimination between the enantiotopic C-H groups on the epoxide ring by deprotonation with an organolithium-ligand complex. 8 However, the exact fates of the individual enantiomeric lithiated epoxide (carbenoid) intermediates might be different in the presence of a chiral, non-racemic ligand.…”