Synlett 2017; 28(20): 2790-2794
DOI: 10.1055/s-0036-1590833
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Star-Shaped Aromatic Derivatives with Chirality Predetermined by Bicyclo[3.3.1]nonane Framework

a   Department of Material Science and Electrical Engineering, Center for Physical Sciences and Technology, Saulėtekio av. 3, Vilnius, 10257, Lithuania   Email: gintautas.bagdziunas@ftmc.lt
,
Sigitas Stončius
b   Department of Organic Chemistry, Center for Physical Sciences and Technology, Akademijos st. 7, Vilnius, 08412, Lithuania
,
Eugenijus Butkus
c   Life Sciences Center, Saulėtekio av. 7, Vilnius, 10257, Lithuania
› Author Affiliations
G.B. and S.S. acknowledge support from the European Social Fund under the Global Grant measure (VP1-3.1-ŠMM-07-K-01-030).
Further Information

Publication History

Received: 17 May 2017

Accepted after revision: 15 June 2017

Publication Date:
14 July 2017 (online)


Dedicated to Professor Viktoras A. Sniečkus on the occasion of his 80th anniversary

Abstract

Star-shaped aromatic derivatives of bicyclo[3.3.1]nonane with predetermined chirality were synthesized by employing the Suzuki and Sonogashira reactions. The C 3-symmetric trifunctional aromatic derivatives based on the lateral bicyclo[3.3.1]nonene moiety possess unique molecular structures. The chiroptical properties of the star-shaped compounds and the corresponding monomeric derivatives were studied, and the absolute configuration was confirmed by using the empirical octant rule for the carbonyl chromophore and the sector rule for the aromatic chromophore.

Supporting Information

 
  • References and Notes

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  • 10 6-Oxobicyclo[3.3.1]non-2-en-2-yl Derivatives 1–3; General Procedure A solution of LiHMDS (1.2 equiv) in toluene was added dropwise over 20 min to a solution of bicyclo[3.3.1]nonane-2,6-dione (1 equiv) in anhyd THF (5 mL) under argon at –40 °C, and the mixture was stirred at –40 °C for 40 min. The mixture was then cooled to –70 °C, and N-(5-chloro-2-pyridyl)bis(trifluoromethanesulfonimide), Ts2O, or (EtO)2POCl (1.1 equiv) was added as appropriate. The mixture was stirred at a low temperature for 2 h, then allowed to warm slowly to r.t. over 12 h. Sat. aq NH4Cl (10 mL) was added, and the mixture was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography.
  • 12 Suzuki Reaction: Typical ProcedureA mixture of monotriflate 3 (1 equiv), PhB(OH)2 (1.5 equiv), Pd(PPh3)4 (3 mol%), and CsF (2 equiv) was dissolved in dry DMF (2 mL) under argon. The solution was stirred at r.t. in the closed vessel for 24 h. The mixture was then filtered through a Celite pad that was washed with CH2Cl2. The combined organic phases were washed with H2O (2 × 10 mL) and brine (2 × 10 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography.Sonogashira Reaction: General ProcedureA mixture of monotriflate 3 (1 equiv), Pd(PPh3)4 (3 mol%) and AgOTf (15 mol%) was dissolved in dry THF (2 mL) under argon. Ethynylbenzene (2 equiv) or 1,3,5-triethynylbenzene (0.3 equiv) and Et3N (5 equiv) were added, and the mixture was stirred at 50 °C for 12 h. The mixture was then filtered through a Celite pad that was washed with CH2Cl2. The combined organic phases were washed with H2O (2 × 10 mL) and brine (2 × 10 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography.
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  • 15 Characterization Data for Representative Compounds(+)-(S, 5)-6-Oxobicyclo[3.3.1]non-2-en-2-yl Triflate (3)Colorless oil; yield: 163 mg (81%); [α]D +48.1 (c 1.04, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 5.91 (dd, J = 4.8, 2.8 Hz, 1 H), 2.73 (dd, J = 6.7, 3.4 Hz, 2 H), 2.57 (ddd, J = 19.2, 7.0, 2.8 Hz, 1 H), 2.47–2.35 (m, 2 H), 2.21–1.87 (m, 5 H). 19F NMR (282 MHz, CDCl3): δ = –74.49. 13C NMR (75 MHz, CDCl3): δ = 212.1, 149.5, 118.6 (q, J = 320 Hz), 117.5, 43.0, 35.9, 32.7, 31.6, 28.4, 27.8. HRMS (EI): m/z calcd for C10H11F3O4S: 284.2521; found: 284.2532.(+)-(1S,5S)-6-Phenylbicyclo[3.3.1]non-6-en-2-one (4)Colorless crystals; yield: 36 mg (91%); mp 37–38 °C; [α]D +29.4 (c 1.09, CHCl3); IR: 2932, 1708, 1446, 761, 735, 699 cm–1; 1H NMR (300 MHz, CDCl3): δ = 7.52 – 7.21 (m, 5 H), 6.19 (dd, J = 4.5, 2.9 Hz, 1 H), 3.10–3.06 (m, 1 H), 2.76–2.78 (m, 1 H), 2.71–2.04 (m, 6 H), 2.04–1.84 (m, 2 H); 13C NMR (75 MHz, CDCl3): δ = 215.0, 141.0, 140.0, 128.8, 127.5, 125.9, 123.5, 44.2, 36.4, 32.2, 31.0, 30.9, 30.1. UV (EtOH): λmax (log ε) = 244 (4.09). CD (EtOH): λmax (Δε) = 247 (–3.0), 289 (1.5).(+)-(1S,5S)-6-(Phenylethynyl)bicyclo[3.3.1]non-6-en-2-one (5)Yellow oil; yield: 43 mg (88) [α]D +28.9 (c 1.14, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.55–7.28 (m, 5 H), 6.31 (dd, J = 4.6, 3.0 Hz, 1 H), 2.79–2.71 (m, 1 H), 2.71–2.63 (m, 1 H), 2.62–1.85 (m, 8 H). 13C NMR (75 MHz, CDCl3): δ = 214.1, 133.2, 131.6, 128.4, 124.1, 123.4, 89.6, 88.5, 43.7, 36.0, 33.4, 30.9, 30.4. HRMS (EI): m/z calcd for C17H16O: 236.1201; found: 236.1224. UV (CH2Cl2): λmax (log ε) = 291 (3.90), 275 (3.99). CD (EtOH): λmax (Δε) = 299 (5.0), 270 (–0.50). (+)-(1S,1′S,1′′S,5S,5′S,5′′S)-6,6′,6′′-(Benzen-1,3,5-triyl)tris(bicyclo[3.3.1]non-6-en-2-one) (6)Colorless amorphous material; yield: 34 mg (70%); mp > 250 °C (dec.); [α]D +18.7 (c 1.07, CHCl3); IR: 3406, 1707, 1589, 1447, 1186, 1106, 1066 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.36 (s, 3 H), 6.22 (dd, J = 4.3, 2.8 Hz, 3 H), 3.10 (m, 3 H), 2.80 (m, 3 H), 2.72 – 2.07 (m, 18 H), 1.98 (m, 6 H). 13C NMR (75 MHz, CDCl3): δ = 214.6, 141.4, 140.0, 124.1, 122.4, 77.6, 77.2, 76.7, 44.1, 36.2, 32.1, 31.2, 30.8, 30.0. HRMS (EI): m/z calcd for C33H36O3: 480.2664; found: 480.2668. UV (CH2Cl2): λmax (log ε) = 249 (4.41), 314 (3.42). CD (CH2Cl2): λmax (Δε) = 245 (–3.0), 308 (4.1).(+)-(1S,1′S,1′′S,5S,5′S,5′′S)-6,6′,6′′-(Benzen-1,3,5-triyltris(ethyn- 1,2-diyl))tris(bicyclo[3.3.1]non-6-en-2-one) (8)Colorless amorphous material; yield: 97 mg (86%); mp > 250 °C (dec.); [α]D +145 (c 1.23, CHCl3). IR: 2200, 1709, 1576, 1104 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.43 (s, 3 H), 6.32 (dd, J = 4.3, 3.1 Hz, 3 H), 3.74–3.68 (m, 3 H), 2.81–2.70 (m, 3 H), 2.69–1.70 (m, 24 H). 13C NMR (75 MHz, CDCl3): δ = 213.6, 134.2, 133.8, 124.1, 123.8, 86.9, 43.6, 36.0, 33.3, 30.8, 30.3, 29.9. HRMS (EI): m/z calcd for C39H36O3: 552.2664; found: 552.2659. UV (CH2Cl2): λmax (log ε) = 297 (4.63), 281 (4.63), 268 (shoulder, 4.49). CD (CH2Cl2): λmax (Δε) = 303 (20.5), 274 (–4.4).(+)-(1S,1S,1′′S,5S,5′S,5′′S)-6,6′,6′′-(Benzen-1,3,5-triyltris(phenyl-1,4-diyl))tris(bicyclo[3.3.1]non-6-en-2-one) (10)Colorless amorphous material; yield: 20 mg (49%); mp > 250 °C (dec.); [α]D +81.8 (c 1.98, CHCl3); IR: 1708, 1512, 813 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.80 (s, 3 H), 7.63 (dd, J = 41.7, 8.5 Hz, 12 H), 6.30 (dd, J = 4.4, 2.9 Hz, 3 H), 3.21–3.08 (m, 3 H), 2.88–2.77 (m, 3 H), 2.68 (dd, J = 18.1, 5.7 Hz, 3 H), 2.58–1.40 (m, 21 H). 13C NMR (75 MHz, CDCl3): δ = 214.8, 142.0, 140.0, 139.9, 139.3, 127.5, 126.2, 124.9, 123.7, 44.1, 36.2, 32.1, 30.8, 30.8, 30.1. HRMS (EI): m/z calcd for C51H48O3: 708.3603; found: 708.3605. UV (CH2Cl2): λmax (log ε) = 287 (4.86). CD (CH2Cl2): λmax (Δε) = 308 (18.9), 277 (–23.7).
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