An ethynyl-substituted 1,5,7-trimethyl-3-azabicyclo[3.3.1]nonan-2-one as a versatile precursor for chiral templates and chiral photocatalysts

Synlett

Volumn , Issue 10, 2010, Pages 1493-1496

  Voss, Felix ^a   Bach, Thorsten ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

Cycloadditions; Cyclobutanes; Enantioselectivity; Heterocycles; Organocatalysis; Photochemistry

Indexed keywords

1,5,7 TRIMETHYL 3 AZABICYCLO[3.3.1]NONAN 2 ONE; ALKYNE; AZIDE; HALIDE; IODOBENZENE; LACTAM; QUINOLONE DERIVATIVE; TRIFLUOROMETHANESULFONIC ACID; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; CHIRALITY; CYCLOADDITION; ENANTIOMER; ENANTIOSELECTIVITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; PHOTOCHEMISTRY; SEPARATION TECHNIQUE; SONOGASHIRA REACTION; SYNTHESIS;

EID: 77953255632     PISSN: 09365214     EISSN: 14372096     Source Type: Journal    
DOI: 10.1055/s-0029-1219920     Document Type: Article

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32. Representative Procedure for the Synthesis of 10c An oven-dried Schlenk tube was charged with alkyne 5 (20.0 mg, 97.4 mmol), triflate 8c (34.0 mg, 106 mmol) Pd(PPh3)4 (11.0 mg, 9.74 mmol), CuI (1.9 mg, 9.74 mmol), and LiCl (24.7 mg, 584 mmol) and was 5 times evacuated and purged with argon. A mixture of DMF (2.3 mL) and Et3N (770 mL, 1.95 mmol) was degassed by 3 freeze-pump-thaw cycles, added to the Schlenk tube, and the resulting suspension was heated to 60 C for 71 h. The reaction mixture was cooled to r.t. and diluted with EtOAc (20 mL) and H2O (15 mL). After separation of the layers the aqueous phase was extracted with EtOAc (3 20 mL), and the combined organic layers were washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the crude product by flash column chromatography (silica gel, pentaneEtOAc = 5:1 to 1:1) yielded compound 10c (33.7 mg, 89.7 mmol, 92%) as a colorless grease. 1H NMR (360 MHz, CDCl3): d = 1.02 (s, 3 H), 1.15 (d, 2J = 13.4 Hz, 1 H), 1.19 (s, 3 H), 1.221.27 (m, 2 H), 1.29 1.34 (m, 5 H), 1.711.96 (m, 8 H), 2.20 (dt, 2J = 13.4 Hz, 4J = 2.1 Hz, 1 H), 2.52 (tt, 3J = 10.3 Hz, 3J = 5.5 Hz, 1 H), 2.712.77 (m, 4 H), 3.12 (d, 2J = 11.6 Hz, 1 H), 3.43 (ddd, 2J = 11.6 Hz, 4J = 3.2 Hz, 4J = 1.5 Hz, 1 H), 5.42 (s, 1 H), 6.96 (s, 2 H) ppm. 13C NMR (90.6 MHz, CDCl3): d = 22.6, 25.6, 29.2, 29.9, 30.4, 30.6, 30.8, 33.8, 36.3, 38.4, 44.3, 48.5, 51.7, 52.4, 79.9, 94.1, 120.6, 128.8, 136.6, 137.7, 176.4 ppm. HRMS: m/z calcd for C26H33NO: 375.2562; found: 375.2564.
33. Representative Procedure for the Synthesis of 11c A round-bottom flask was charged with alkyne 5 (19.6 mg, 95.5 mmol), azide 9c (45.0 mg, 188 mmol), and CuI (1.8 mg, 9.56 mmol) in THF (2.0 mL). Et3N (192 mL, 191 mmol) was added, and the flask was closed with a rubber septum and heated to 50 C for 3 h. The reaction mixture was cooled to r.t. and diluted with EtOAc (15 mL) and H2O (10 mL). After separation of the layers the aqueous phase was extracted with EtOAc (3 15 mL), and the combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the crude product by flash column chromatography (silica gel, EtOAc) yielded compound 11c (42.0 mg, 94.9 mmol, 99%) as a yellow solid. 1H NMR: (360 MHz, CDCl3): d = 1.12 (s, 3 H), 1.29 (s, 3 H), 1.33 (s, 3 H), 1.381.44 (m, 2 H), 1.52 (d, 2J = 14.2 Hz, 1 H), 1.80 (d, 2J = 13.5 Hz, 1 H), 2.71 (d, 2J = 14.2 Hz, 1 H), 3.02 (d, 2J = 12.2 Hz, 1 H), 3.173.28 (m, 2 H), 5.81 (s, 1 H), 7.10 (d, 3J = 9.1 Hz, 1 H), 7.45 (ddd, 3J = 8.0 Hz, 3J = 7.1 Hz, 4J = 1.0 Hz, 1 H), 7.55 (ddd, 3J = 8.5 Hz, 4J = 1.0 Hz, 4J = 0.5 Hz, 1 H), 7.767.81 (m, 1 H), 8.04 (dd, 3J = 9.1 Hz, 4J = 2.7 Hz, 1 H), 8.30 (dd, 3J = 8.0 Hz, 4J = 1.3 Hz, 1 H), 8.47 (s, 1 H), 8.63 (d, 4J = 2.7 Hz, 1 H) ppm. 13C NMR (90.6 MHz, CDCl3): d = 25.7, 29.8, 30.5, 34.6, 37.1, 38.3, 45.2, 47.6, 47.8, 51.9, 116.5, 117.8, 118.5, 118.9, 121.3, 121.6, 124.4, 126.4, 126.9, 133.7, 135.3, 154.6, 154.6, 155.8, 176.2, 176.3 ppm. HRMS: m/z calcd for C26H26N4O3: 442.2005; found: 442.2002.
34. Representative Irradiation Procedure (Table 1, Entry 3) An oven-dried Duran tube was charged with 4-allyloxyquinolone (12, 7.6 mg, 37.9 mmol) and template 10c (35.6 mg, 94.8 mmol) in dry toluene (7.6 mL), and the solution was degassed by three freeze-pump-thaw cycles. The reaction mixture was irradiated under argon at 70 C (l = 300 nm, light source: Rayonet RPR-3000 ) for 3 h, and the solvent was removed in vacuo. Purification of the crude product by flash chromatography (silica gel, pentaneEtOAc = 1:1 to EtOAc) yielded the recovered template 10c (25.6 mg, 68.3 mmol, 72%) and product 13 (6.9 mg, 34.3 mmol, 91%, 72% ee) as colorless solids. The analytical data of product 13 were in agreement with the values previously reported.3b,20,21