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DOI: 10.1055/s-2006-950418
Highly Enantioenriched 2-Azabenzonorbornenes from 7-Azabenzonorbornadienes by Asymmetric Hydroboration-Oxidation and Tandem Deoxygenation-Rearrangement-Electrophile Trapping
Publication History
Publication Date:
08 September 2006 (online)
Abstract
3-exo-Substituted 2-azabenzonorbornenes are accessible from 7-azabenzonorbornadienes in good yields and high enantiomeric excess via asymmetric hydroboration-oxidation, followed by tandem deoxygenation-rearrangement-electrophile trapping and also provide access to substituted aminomethylindenes.
Key words
asymmetric synthesis - radicals - tandem reactions - deoxygenation - rearrangements
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References and Notes
Determined by chiral HPLC analysis: Chiralcel OD column (4.6 × 250 mm); flow rate: 0.9 mL/min; eluted with 1% EtOH in heptane; t R(minor) = 24.3 min, t R(major) = 26.6 min.
16Typical Procedure for Tandem Deoxygenation-Rearrangement-Electrophile Trapping: Xanthate (+)-3 (250 mg, 0.71 mmol) was dissolved in toluene (20 mL) and then heated to reflux. (Me3Si)3SiH (256 mg, 1.1 mmol), AIBN (58 mg, 0.36 mmol) and methyl acrylate (9.6 µL, 1.1 mmol) were dissolved in toluene (4 mL) and were added to the refluxing solution via syringe pump over 100 min. The reaction mixture was allowed to reflux for a further 30 min before being cooled to r.t. and evaporated under reduced pressure. Column chromatography [SiO2; gradient elution 5% → 20% Et2O in PE (bp 30-40 °C)] of the residue gave ester (+)-10 as a colourless oil (131 mg, 56%); R f (Et2O-PE, 1:4) 0.07; [α]D 25 81.0 (c = 1.00, CHCl3). IR (neat): 2977 (m), 1739 (s), 1695 (s), 1462 (m), 1366 (s), 1260 (m), 1170 (s), 1121 (m), 1100 (m), 1074 (m), 1000 (w), 910 (w), 839 (w), 757 (m) cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.05-7.39 (m, 4 H, aromatic CH), 4.86, 4.98 (0.25 H, 0.75 H, rotamers, CH), 3.67 (s, 3 H, OCH3), 2.92-3.04, 2.79-2.92 (m, 0.75 H, 0.25 H, rotamers CH), 2.59-2.44 (m, 2 H, CH2), 2.08-2.30 (overlapping m, 2 H, 2 × CH), 1.79-1.98 (m, 1 H, CH2), 1.71-1.79 (m, 1 H, CH2), 1.35-1.42, 1.26-1.35 [m, 10 H, C(CH3)3, CH]. 13C NMR (100 MHz, CDCl3): δ = 174 (CO), 157 (CO), 146 (quat. aromatic), 144 (quat. aromatic), 127 (aromatic CH), 126 (aromatic CH), 122, 121 (rotamers, aromatic CH), 120 (aromatic CH), 79.5 [C(CH3)3], 62.7, 61.7 (rotamers, CH), 59.8 (CH), 51.8, 51.5 (rotamers, CH3), 48.2, 47.8 (rotamers, CH), 45.3, 44.8 (rotamers, CH2), 32.5, 31.9 (rotamers, CH2), 30.5, 30.3 (rotamers, CH2), 28.5, 28.3 [rotamers, C(CH3)3]. MS (CI+): m/z (%) = 332 (100) [M + H]+, 276 (43), 232 (77), 214 (12), 200(5), 183 (4), 172 (10), 158 (15), 144 (17), 130 (11), 116 (26). HRMS: m/z calcd for C19H26NO4: 332.1865; found: 332.1866.
17This is consistent with the observation that increasing the equivalents of the alkene leads to lower yields of 12.
21Determined by chiral GC analysis: Chirasil Dex-CD column; flow rate: 1.0 mL/min; t R (minor, not observed in the enantioenriched product) = 540 min, t R(major) = 544 min.