Highly Enantioenriched 2-Azabenzonorbornenes from 7-Azabenzonorbornadienes by Asymmetric Hydroboration-Oxidation and Tandem Deoxygenation-Rearrangement-Electrophile Trapping

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

References and Notes

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10

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.

16

Typical 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.

17

This is consistent with the observation that increasing the equivalents of the alkene leads to lower yields of 12.

21

Determined 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.