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.

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.

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15b For a recent review, see: Chatgilialoglu C. Organosilanes in Radical Chemistry   Wiley; Chichester: 2004. 

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.

18 Kopping B. Chatgilialoglu C. Zehnder M. Giese B. J. Org. Chem.  1992,  57:  3994 

19 Resolution of alcohol 14 could not be achieved using chiral HPLC or GC, but oxidation with TPAP ( Griffith WP. Ley SV. Whitcombe GP. White A. J. Chem. Soc., Chem. Commun.  1987,  1625 ) to the corresponding (+)-ketone (79%) allowed determination by chiral HPLC: Chiralcel OD column (4.6 × 250 mm); flow rate: 0.2 mL/min; eluted with 1% EtOH in heptane; t _{R (}major) = 112 min, t _R (minor, not observed in the enantioenriched product) = 139 min

20 Swenton JS. Oberdier J. Rosso PD. J. Org. Chem.  1974,  39:  1038 

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.

22 Trivedi BK. inventors; Eur. Patent Appl., EP  335375.  ; Chem. Abstr. 1990, 112, 178376

23a Curran DP. Synthesis  1988,  417 

23b Curran DP. Synthesis  1988,  489