Enantioselective, intermolecular [2+2] photocycloaddition ... · Enantioselective, intermolecular [2+2] photocycloaddition reactions of 3-acetoxyquinolone: Total synthesis of (−−−−)-pinolinone

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Enantioselective, intermolecular [2+2] photocycloaddition

reactions of 3-acetoxyquinolone: Total synthesis of (−−−−)-

pinolinone

Electronic Supplementary Information (ESI)

Florian Mayr, Christian Wiegand and Thorsten Bach*

Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstrasse 4,

85747 Garching, Germany

1. Synthetic procedures and analytical data of new compounds .............................................. S2

2. References for the Supporting Information ........................................................................ S32

3. NMR spectra of new compounds ....................................................................................... S33

4. HPLC traces of racemic and enantioenriched products ..................................................... S55

Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2014

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1. Synthetic procedures and analytical data of new compounds

General information

All reactions sensitive to air or moisture were carried out in flame-dried glassware under a

positive pressure of argon using standard Schlenk techniques. Dry tetrahydrofuran (THF),

dichloromethane (CH2Cl2) and diethylether (Et2O) were obtained from an MBRAUN MB-SPS

800 solvent purification system. Other dry solvents were obtained from Acros in the highest

purity available and used without further purification. Technical solvents used for aqueous

workup and for column chromatography [n-pentane (pentane), ethyl acetate (EtOAc), diethyl

ether (Et2O), dichloromethane (CH2Cl2), methanol (MeOH)] were distilled prior to use.

Photochemical experiments were performed in Duran tubes (diameter: 1.2 cm, volume 10 mL

or 20 mL each; diameter 2.0 cm, volume 60 mL) in an RPR-100 photochemical reactor

(Southern New England Ultra Violet Company, Branford, CT, USA) equipped with

flourescence lamps: (λ = 366 nm). Prior to irradiation, the mixture was deoxygenated by

purging with argon in an ultrasonicating bath for 15 minutes before alkene were added to the

mixture.

Flash Chromatography was performed on silica gel 60 (Merck, 230-240 mesh) with the eluent

mixtures given for the corresponding procedures. Thin-layer Chromatography (TLC) was

performed on silica-coated glass plates (silica gel 60 F 254). Compounds were detected by

UV (λ = 254 nm, 366 nm) and CAM solution (cerium ammonium molybdate). All solvents

for chromatography were distilled prior to use.

Analytical HPLC was performed using a chiral stationary phase (Daicel ChiralCell, Chemical

Industries, flow rate: 1.0 mL/min, type and eluent is given for the corresponding compounds)

and UV detection (λ = 210 nm or 254 nm) at 20 °C.

IR spectra were recorded on a JASCO IR-4100 (ATR), MS and HRMS measurements were

performed on a Finnigan MAT 8200 (EI). 1H,

13C and

31P NMR spectra were recorded at

300 K either on a Bruker AV-250, a Bruker AV-360 or a Bruker AV-500 spectrometer.

Chemical shifts are reported on parts per million (ppm) relative to residual CDCl3

(δH = 7.26 ppm and δC = 77.0 ppm), DMSO-δ6 (δH = 2.50 ppm and δC = 39.5 ppm). All

coupling constants (J) are reported in Hertz (Hz). Apparent multiplets that occur as a result of

accidental equality of coupling constants those of magnetically non-equivalent protons are

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marked as virtual (virt.). Differentiable protons in cyclic systems are signed with Hu = "up"

and Hd = "down". The relative configuration of chiral products and the multiplicity of the

13C-

NMR signals were determined by two-dimensional NMR experiments (COSY, NOESY,

HSQC, HMBC).

2-Chloroquinolin-3-ol

To a solution of di-iso-propylamine (4.29 mL, 3.10 g, 30.6 mmol, 1.0 equiv.) in THF (75 mL)

n-butyllithium (12.2 ml, 2.5 M, 30.6 mmol, 1.0 equiv.) was added slowly at −20 °C. After the

addition the mixture was allowed to warm up to 0 °C. After one hour at this temperature the

mixture was cooled down to −78 °C. 2-Chloroquinoline (5.00 g, 30.6 mmol, 1.0 equiv.)

dissolved in THF (15 mL) was added dropwise. After stirring for two hours at this

temperature trimethyl borate (3.40 mL, 3.21 g, 30.6 mmol, 1.0 equiv.) was added and the

mixture was stirred for two hours at −78 °C. Subsequently the reaction was quenched with

aqueous THF (1 mL H2O in 6 mL THF). Water (100 mL) and Et2O (100 mL) were added. For

the aqueous layer the pH-value was adjusted to pH = 4 by hydrochloric acid (36%). The

aqueous layer was extracted with Et2O (3 × 100 mL). The combined organic layers were

washed with brine, dried over sodium sulfate and filtered. The solvent was removed under

reduced pressure. The residue was dissolved in Et2O (150 mL) and aqueous ammonium

chloride (4.00 g in 160 mL H2O) was added. Under stirring hydrogen peroxide (40 mL, 35%)

was added slowly. The mixture was stirred for four hour at room temperature. The colourless

solid was collected by filtration, washed with water (150 mL) and dried under reduced

pressure. The title compound (3.85 g, 21.4 mmol, 70%) was isolated as colourless solid.

TLC: Rf = 0.89 (EtOAc-MeOH = 9:1) [UV].

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1H-NMR (360 MHz, DMSO-d6): δ (ppm) = 7.50-7.58 (m, 2 H, H-6, H-7), 7.67 (s, 1 H,

H-4), 7.82-7.86 (m, 2 H, H-5, H-8), 11.08 (br s, 1 H, OH).

13C-NMR (93 MHz, DMSO-d6): δ (ppm) = 117.7 (d, C-4), 126.3 (d, C-5), 127.0

(d, C-7), 127.1 (d, C-6), 127.4 (d, C-8), 128.4 (s, C-4a), 141.2 (s, C-8a), 142.3 (s, C-2), 147.0

(s, C-3).

Analytical data are in agreement with literature data.[1]

3-Hydroxyquinolin-2(1H)-one

2-Choroquinolin-3-ol (3.85 g, 21.4 mmol, 1.0 equiv.) was suspended in aqueous hydrochloric

acid (6 N, 68 mL) and stirred for 24 hours under reflux. After the reaction was complete, the

mixture was cooled to room temperature and filtered. The residue was washed with water

(100 mL) and dried under reduced pressure. The title compound (2.90 g, 18.0 mmol, 84%)

was isolated as colourless solid.

1H-NMR (250 MHz, DMSO-d6): δ (ppm) = 7.08-7.14 (m, 1 H, H-6), 7.09 (s, 1 H, H-4), 7.24-

7.32 (m, 2 H, H-7, H-8), 7.47-7.50 (m, 1 H, H-5), 9.46 (s, 1 H, OH), 12.01 (s, 1 H, NH).

13C-NMR (63 MHz, DMSO-d6): δ (ppm) = 112.4 (d, C-4), 114.7 (d, C-8), 120.7

(s, C-4a), 122.0 (d, C-6), 125.8 (d, C-5), 126.3 (d, C-7), 133.5 (s, C-8a), 146.2 (s, C-3), 158.6

(s, C-2).


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2-Oxo-1,2-dihydroquinolin-3-yl acetate (4)

3-Hydroxyquinolin-2(1H)-one (2.41 g, 14.5 mmol, 1.0 equiv.) was dissolved in dry pyridine

(60 mL) and acetic anhydride (4.12 mL, 4.45 g, 45.6 mmol, 2.9 equiv.) was added. The

mixture was stirred at room temperature for 24 hours. After the reaction was complete, the

mixture was poured on ice water (250 mL) and filtered. The residue was recrystallised in

ethanol (100 mL) and filtered. The title product 4 (2.13 g, 10.5 mmol, 72%) was isolated as

colourless solid.

TLC: Rf = 0.23 (P/EtOAc = 1/1) [UV, CAM].

1H-NMR (250 MHz, DMSO-d6): δ (ppm) = 2.28 (s, 3 H, OCCH3), 7.22 (ddd,

3J = 8.5 Hz,

3J = 7.2 Hz,

4J = 1.5 Hz, 1 H, H-6), 7.34 (dd,

3J = 8.5 Hz,

4J = 1.5 Hz, 1 H, H-8),

7.51 (ddd, 3J = 8.5 Hz,

3J = 7.2 Hz,

4J = 1.5 Hz, 1 H, H-7), 7.66 (dd,

3J = 8.5 Hz,

4J = 1.5 Hz,

1 H, H-5), 7.81 (s, 1 H, H-4), 12.2 (br s, 1 H, NH).

13C-NMR (63 MHz, DMSO): δ (ppm) = 20.3 (q, C-10), 115.1 (d, C-8), 118.3 (s, C-4a), 122.3

(d, C-6), 127.7 (d, C-5), 128.3 (d, C-4), 129.9 (d, C-7), 136.9 (s, C-8a), 140.6 (s, C-3), 156.6

(s, C-2), 168.3 (s, C-9).


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[2+2] Photocycloaddition of quinolones with alkenes

General procedure for racemic intermolecular [2+2] photocycloadditions:

A solution of quinolone 4 in acetonitrile was purged with argon in an ultrasonicating bath for

15 minutes. The solution was divided in phototubes and the respective alkene 5a-f (20 equiv.)

was added to the solution in each tube. The mixture was irradiated at room temperature at

λ = 366 nm (2-3 hours). The solvent was removed under reduced pressure and the crude

material was subjected to flash column chromatography using an appropriate solvent system,

as described for each individual procedure.

General procedure for enantioselective intermolecular [2+2] photocycloadditions:

A solution of quinolone 4 (49.0 µmol) and template 6 (123 µmol, 2.5 equiv.) in toluene

(10 mL) was purged with argon in an ultrasonicating bath for 15 minutes. The respective

alkene 5a-f (20 equiv.) was added and the solution was transferred in a phototube. The

mixture was irradiated at −70 °C for 3 to 12 hours (described in each individual procedure) at

λ = 366 nm. The solvent was removed under reduced pressure and the crude material was

subjected to flash column chromatography using appropriate solvent system, as described for

each individual procedure.

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(2aS,8bS)-3-Oxo-1,3,4,8b-tetrahydrocyclobuta[c]quinoline-1,2a(2H)-diyl diacetate (3a)

Racemic procedure:

Using the general procedure a mixture of quinolone 4 (10.0 mg, 49.0 µmol, 1.0 equiv.) and

vinyl acetate 5a (95.0 µL, 85.0 mg, 984 µmol, 20 equiv.) in acetonitrile (10 mL) was

irradiated for three hours. Purification of the crude product by flash column chromatography

on silica (∅ 18 × 1.5 cm) eluting with EtOAc-pentane (3:2) gave the title product 3a

(13.7 mg, 47.0 µmol, 96%) as a 72:28 mixture (by 1

H-NMR spectroscopy) of two

diastereomers as a colourless solid.

Enantioselective procedure:

Following the general procedure a solution of quinolone 4 (10.0 mg, 49.0 µmol, 1.0 equiv.)

and chiral template 6 (44.0 mg, 123 µmol, 2.5 equiv.) in toluene (10 mL) was irradiated after

addition of vinyl acetate 5a (95.0 µL, 85.0 mg, 984 µmol, 20 equiv.) for three hours at

−70 °C. Purification of the crude product by flash column chromatography on silica

(∅ 18 × 1.5 cm) eluting with CH2Cl2-pentane-MeOH (29:70:1) gave the title product 3a

(10.5 mg, 36.4 µmol, 74%) as colourless solid as a 75:25 mixture of two diastereomers (by

1H-NMR spectroscopy).

m.p.: 175 °C.

TLC: Rf = 0.42 (EtOAc-pentane = 3:2) [UV, CAM].

IR (ATR): ν̃ (cm-1

) = 3237 (br), 2928 (w), 1739 (m, C=O), 1681 (br, C=O), 1595 8m), 1490

(m), 1371 (m), 1225 (s, C−O), 1197 (s), 1077 (m), 1028 (br), 755 (m), 733 (m).

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Major isomer:

1H-NMR (500 MHz, CDCl3): δ (ppm) = 1.75 (s, 3 H, H-2´), 2.15 (s, 3 H, H-2´´), 2.80 (dd,

2J

= 14.3 Hz, 3J = 5.6 Hz, 1 H, H-2

u), 3.09 (ddd,

2J = 14.3 Hz,

3J = 8.1 Hz,

4J = 3.3 Hz, 1 H, H-

2d), 4.10 (dd,

3J = 7.8 Hz,

4J = 3.3 Hz, 1 H, H-8b), 5.57 (virt. td,

3J = 7.8 Hz,

3J = 5.6 Hz 1 H,

H-1), 6.77 (dd, 3J = 7.5 Hz,

4J = 1.1 Hz, 1 H, H-5), 6.91 (d,

3J = 7.5 Hz, 1 H, H-8), 6.98 (td,

3J = 7.5 Hz,

4J = 1.1 Hz, 1 H, H-7), 7.19 (td,

3J = 7.5 Hz,

4J = 1.1 Hz, 1 H, H-6), 8.26 (s, 1 H,

H-4).

13C-NMR (91 MHz, CDCl3): δ (ppm) = 20.6 (q, C-2´), 21.0 (q, C-2´´), 38.8 (t, C-2), 50.2 (d,

C-8b), 66.7 (d, C-1), 72.6 (s, C-2a), 115.8 (d, C-5), 117.7 (s, C-8a), 123.4 (d, C-7), 128.5 (d,

C-6), 129.5 (d, C-8), 136.9 (s, C-4a), 167.0 (s, C-3), 170.3 (s, C-1´), 170.4 (s, C-1´´).

Minor isomer:

13C-NMR (91 MHz, CDCl3): δ (ppm) = 20.6 (1, C-2´), 21.0 (q, C-2´´), 40.4 (t, C-2), 53.3 (d,

C-8b), 68.6 (d, C-1), 69.9 (s, C-2a), 115.9 (d, C-5), 121.7 (s, C-8a), 124.0 (d, C-7), 127.3 (d,

C-8), 128.5 (d, C-6), 136.1 (s, C-4a), 168.2 (s, C-3), 170.1 (s, C-1´), 170.4 (s, C-1´´).

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MS (EI, 70 eV) m/z (%) = 289 (5) [M+], 230 (10) [(C13H12NO3)

+], 188 (80) [(C11H9NO2)

+],

161 (100) [(C9H6NO2)+], 159 (40), 149 (25), 84 (35), 57 (33), 43 (82).

HRMS (EI): C15H15NO5 calc.: [M+]: 289.0945

found: [M+]: 289.0947.

Chiral HPLC: tR [racemate] = 28.4 min, 32.2 min, 39.2 min, 44.5 min; tR [ent-3a] =

31.7 min, 38.6 min, tR [3a] = 28.2 min, 44.0 min; 87% ee, 89% ee (AD-H-250 × 4.6 mm, n-

hexane/i-PrOH = 90:10, 1 mL/min, λ = 210 nm).

Specific rotation: [α]D20

= −163.8 (c = 0.53, MeOH).

(2aS,8bR)-1,1-Dichloro-3-oxo-1,3,4,8b-tetrahydrocyclobuta[c]quinolin-2a(2H)-yl acetate

(3b)

Racemic procedure:

Using the general procedure a mixture of quinolone 4 (10.0 mg, 49.0 µmol, 1.0 equiv.) and

1,1-dichloroethene 5b (80.0 µL, 94.0 mg, 984 µmol, 20 equiv.) in acetonitrile (10 mL) gave

the crude product. Purification of the crude product by flash column chromatography on silica

(∅ 18 × 1.5 cm) eluting with EtOAc-pentane (2:3) gave the title compound 3b (14.5 mg,

49.0 µmol, quant.) as colourless solid.


Following the general procedure a solution of quinolone 4 (10.0 mg, 49.0 µmol, 1.0 equiv.),

template 6 (44.0 mg, 123, µmol, 2.5 equiv.) and 1,1-dichloroethene 5b (80.0 µL, 94.0 mg,

984 µmol, 20 equiv.) in toluene (10 mL) was irradiated for three hours at −74 °C. Purification

of the crude product by flash column chromatography on silica (∅ 18 × 1.5 cm) eluting with

S10

EtOAc-pentane (2:3) gave the title compound 3b (14.8 mg, 49.0 µmol, quant.) as colourless

solid.

m.p.: 178 °C.



) = 3368 (w), 2957 (w), 1749 (m, C=O), 1684 (s, C=O), 1483 (m), 1366

(br), 1235 (s, C−O), 1069 (m), 1007 (m), 764 (s).

1H-NMR (500 MHz. CDCl3): δ (ppm) = 2.13 (s, 3 H, H-2´), 3.68 (d,

2J = 15.2 Hz, 1 H, H-2

u),

3.72 (dd, 2J = 15.2 Hz,

4J = 1.6 Hz, 1 H, H-2

d), 4.49 (s, 1 H, H-8b), 6.85 (dd,

3J = 7.5 Hz,

4J = 1.3 Hz, 1 H, H-5), 7.10 (td,

3J = 7.5 Hz,

4J = 1.3 Hz, 1 H, H-7), 7.16 (dd,

3J = 7.5 Hz,

4J = 1.5 Hz, 1 H, H-8), 7.29 (td,

3J = 7.5 Hz,

4J = 1.5 Hz. 1 H, H-6), 8.79 (s, 1 H, H-4).

13C-NMR (91 MHz, CDCl3): δ (ppm) = 20.5 (q, C-2´), 56.5 (t, C-2), 64.7 (d, C-8b), 69.6 (s,

C-2a), 80.3 (s, C-1), 116.1 (d, C-5), 118.4 (s, C-8a), 124.0 (d, C-7), 128.3 (d, C-8), 129.7 (d,

C-6), 137.0 (s, C-4a), 166.8 (s, C-3), 170.2 (s, C-1).

MS (EI, 70 eV) m/z (%) = 299 (2) [M+], 203 (7) [(C11H9NO3)

+], 195 (4), 162 (10), 161 (100)

[(C9H6NO2)+], 124 (15), 109 (15), 86 (20), 84 (33).

HRMS (EI): C13H11NO3Cl2: calc.: [M+]: 299.0111

found: [M+]: 299.0105.

Chiral HPLC: tR [racemate] = 35.5 min, 38.0 min; tR [3b] = 37.7 min, tR [ent-3b] = 40.0 min,

57% ee (AD-H, 250 × 4.6 mm, n-hexane/i-PrOH = 95:5, 1 mL/min, λ = 210 nm).


= −108.8 (c = 0.69, MeOH)

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(2aS,8bR)-1,1-Diethyl-3-oxo-1,3,4,8b-tetrahydrocyclobuta[c]quinolin-2a(2H)-yl acetate

(3c)

Racemic procedure:

Using the general procedure a solution of quinolone 4 (10.0 mg, 49.0 µmol, 1.0 equiv.) in

acetonitrile (10 mL) with 2-ethyl-1-butene 5c (120 µL, 83.0 mg, 984 µmol, 20 equiv.) gave

the crude product. Purification by flash column chromatography on silica (∅ 18 × 1.5 cm)

eluting with EtOAc-pentane (2:3) gave the title product 3c (8.70 mg, 30.0 µmol, 62%) as

colourless solid.



template 6 (44.0 mg, 123 µmol, 2.5 equiv.) and 2-ethyl-1-butene 5c (120 µL, 83.0 mg,

984 µmol, 20 equiv.) in toluene (10 mL) gave the crude product. Purification by flash column

chromatography (∅ 18 × 1.5 cm) eluting with CH2Cl2-pentane-MeOH (29:70:1) and a second

flash column chromatography (∅ 18 × 1.5 cm) eluting with EtOAc-pentane (1:1) gave the

title product 3c (4.00 mg, 14.0 µmol, 29%) as colourless solid.

m.p.: 148 °C.

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) = 2967 (w), 2924 (w), 1746 (m, C=O), 1682 (s, C=O), 1593 (w), 1493

(m), 1391 (m), 1366 (m), 1229 (s, C−O), 1088 (m), 1022 (m), 755 (s).

1H-NMR (500 MHz CDCl3): δ (ppm) = 0.61 (t,

3J = 7.6 Hz, 3 H, H-2´´), 0.93 (t,

3J = 7.3 Hz,

3 H, H-2´), 1.03 (dq, 2J = 15.0 Hz,

3J = 7.6 Hz, 1 H, H-1´´), 1.12 (dq,

2J = 15.0 Hz,

3J = 7.8 Hz, 1 H, H-1´´), 1.63-1.75 (m, 2 H, H-1´), 2.10 (s, 3 H, H-2´´´), 2.38 (d,

2J = 14.0 Hz,

1 H, H-2u), 2.50 (dd,

2J = 14.0 Hz,

4J = 1.2 Hz, 1 H, H-2

d), 3.47 (s, 1 H, H-8b), 6.47 (d,

3J = 7.6 Hz, 1 H, H-5), 6.93-7.01 (m, 2 H, H-7, H-8), 7.14 (td,

3J = 7.6 Hz,

4J = 2.2 Hz, 1 H,

H-6), 8.14 (s, 1 H, H-4).

13C-NMR (91 MHz, CDCl3): δ (ppm) = 7.3 (q, C-2´´), 8.2 (q, C-2´), 20.8 (q, C-2´´´), 25.5 (t,

C-1´´), 32.4 (t, C-1´), 40.4 (s, C-1), 42.5 (t, C-2), 53.2 (d, C-8b), 71.7 (s, C-2a), 115.6 (d, C-

5), 121.4 (s, C-8a), 123.4 (d, C-7), 127.6 (d, C-6), 128.6 (d, C-8), 136.7 (s, C-4a), 169.3 (s, C-

3), 170.7 (s, C-1´´´).

MS (EI, 70 eV) m/z (%) = 287 (1) [M+], 228 (5), 203 (6) [(C11H9NO3)

+], 195 (6), 162 (8), 161

(100) [(C9H6NO2)+], 152 (6), 86 (15), 84 (25), 49 (17).

HRMS (EI): C17H21NO3: calc.: [M+]: 287.1516

found: [M+]: 287.1519.

Chiral HPLC: tR [racemate] = 16.4 min, 21.1 min; tR [3c] = 16.9 min, tR [ent-3c] = 21.8 min,



= −182.4 (c = 0.21, MeOH).

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(2aR,8bR)-1,1,2,2-Tetramethyl-3-oxo-1,3,4,8b-tetrahydrocyclobuta[c]quinolin-2a(2H)-yl

acetate (3d)

Racemic procedure:

Using the general procedure a solution of quinolone 4 (10.0 mg, 49.0 µmol, 1.0 equiv.) and

2,3-dimethyl-2-butene 5d (100 µL, 83.0 mg, 984 µmol, 20 equiv.) in acetonitrile (10 mL) was

irradiated for three hours. Purification of the crude product by flash column chromatography

on silica (∅ 18 × 1.5 cm) eluting with EtOAc-pentane (2:3) gave the title product 3d

(14.5 mg, 49.0 µmol, quant.) as colourless solid.



template 6 (44.0 mg, 123 µmol, 2.5 equiv.) and 2,3-dimethyl-2-butene 5d (100 µL, 83.0 mg,

984 µmol, 20 equiv.) in toluene (10 mL) was irradiated for three hours. Purification of the

crude product by flash column chromatography on silica (∅ 18 × 1.5 cm) eluting with

EtOAc-pentane (2:3) gave the title product 3d (14.2 mg, 49.0 µmol, quant.) as colourless

solid.

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m.p.: 182 °C.



) = 2991 (w), 1738 (m, C=O), 1677 (s, C=O), 1595 (m), 1495 (m), 1366

(br), 1242 (br, C−O), 1118 (m), 1037 (m), 746 (s).

1H-NMR (500 MHz, CDCl3): δ (ppm) = 0.68 (s, 3 H, H-1´´´), 1.09 (s, 3 H, H-2´´´), 1.22 (s,

3 H, H-1´´), 1.31 (s, 3 H, H-2´´), 2.08 (s, 3 H, H-2´), 3.36 (s, 1 H, H-8b), 6.70 (dd,

3J = 7.5 Hz,

4J = 1.2 Hz, 1 H, H-5), 6.90 (dd,

3J = 7.5 Hz,

4J = 1.5 Hz, 1 H, H-8), 6.98 (td,

3J = 7.5 Hz,

4J = 1.2 Hz, 1 H, H-7), 7.15 (td,

3J = 7.5 Hz,

4J = 1.5 Hz. 1 H, H-6), 7.76 (s, 1 H,

H-4).

13C-NMR (91 MHz, CDCl3): δ (ppm) = 20.9 (q, C-1´´´), 20.9 (q, C-2´), 21.4 (q, C-2´´´), 21.6

(q, C-2´´), 26.6 (q, C-1´´), 41.2 (s, C-1), 46.6 (s, C-2), 53.0 (d, C-8b), 78.2 (s, C-2a), 115.3 (d,

C-5), 122.0 (s, C-8a), 123.3 (d, C-7), 127.5 (s, C-6), 127.9 (d, C-8), 136.5 (s, C-4a), 167.0 (s,

C-3), 170.6 (s, C1).

MS (EI, 70 eV) m/z (%) = 287 (7) [M+], 227 (7) [(M-C2H4O2)

+], 212 (8), 204 (25), 162 (30),

161 (100) [(C9H6NO2)+], 86 (23), 84 (35).

HRMS (EI): C17H21NO3: calc.: [M+]: 287.1516

found: [M+]: 287.1522.

Chiral HPLC: tR [racemate] = 12.6 min, 15.7 min; tR [3d] = 13.1 min, tR [ent-3d] = 16.4 min;



= −84.2 (c = 0.60, MeOH).

S15

(2aS,8bR)-1,1-Diethoxy-3-oxo-1,3,4,8b-tetrahydrocyclobuta[c]quinolin-2a(2H)-yl acetate

(3e)

Racemic procedure:

Using the general procedure a solution of quinolone 4 (120 mg, 591 µmol, 1.0 equiv.) and

1,1-diethoxyethene 5e (1.56 mL, 1.37 g, 11.8 mmol, 20 equiv.) in acetonitrile (120 mL) was

irradiated for two hours. Purification of the crude product by flash column chromatography on

silica (∅ 25 × 3 cm) eluting with EtOAc-pentane (3:2) gave the title product 3e (133 mg,

416 µmol, 70%) as colourless solid.



template 6 (44.0 mg, 123 µmol, 2.5 equiv.) and 1,1-diethoxyethene 5e (130 µL, 114 mg,

984 µmol, 20 equiv.) in toluene (10 mL) was irradiated for three hours. Purification of the

crude product by flash column chromatography on silica (∅ 18 × 1.5 cm) eluting with

EtOAc-pentane (3:7 → 1:1) gave the title compound 3e (10.5 mg, 33.0 µmol, 67%) as

colourless solid. The mixture of template 6 and quinolone 4 can be separated by a second

flash column chromatography on silica (∅ 20 × 3 cm) eluting with CH2Cl2-pentane-MeOH

(29:70:1).

S16

m.p.: 194 °C.



) = 3194 (w), 3059 (w, NH), 2925 (w), 1747 (s, C=O), 1681 (br, C=O),

1595 (m), 1496 (m), 1401 (m), 1263 (m, C−O), 1237 (s), 1090 (m), 1063 (s), 1041 (s),

765 (s).

1H-NMR (250 MHz, CDCl3): δ (ppm) = 0.88 (t,

3J = 7.5 Hz, 3 H, H-2´´´), 1.24 (t,

3J = 7.5 Hz, 3 H, H-2´´), 2.08 (s, 3 H, H-2´), 2.81 (dd,

2J = 13.7 Hz,

4J = 1.5 Hz, 1 H, H-2

d),

2.84 (d, 2J = 13.7 Hz, 1 H, H-2

u), 3.14-3.20 (m, 1 H, H-1´´´), 3.29-3.35 (m, 1 H, H-1´´´), 3.47-

3.53 (m, 1 H, H-1´´), 3.55-3.61 (m, 1 H, H-1´´), 3.85 (s, 1 H, H-8b), 6.75 (d, 3J = 7.5 Hz, 1 H,

H-5), 6.98 (t, 3J = 7.5 Hz, 1 H, H-7), 7.08 (d,

3J = 7.5 Hz, 1 H, H-8), 7.17 (td,

3J = 7.5 Hz,

4J = 1.6 Hz 1 H, H-6), 8.30 (s, 1 H, H-4).

13C-NMR (63 MHz, CDCl3): δ (ppm) = 15.1 (q, C-2´´´), 15.2 (q, C-2´´), 20.6 (q, C-2´), 44.2

(t, C-2), 56.8 (d, C-8b), 57.2 (t, C-1´´), 57.7 (t, C-1´´´), 69.0 (s, C-2a), 97.4 (s, C-1), 115.5 (d,

C-5), 119.4 (s, C-8a), 123.3 (d, C-7), 127.9 (d, C-6), 128.6 (d, C-8), 137.5 (s, C-4a), 168.3 (s,

C-3), 170.5 (s, C-1´).

MS (EI, 70 eV): m/z (%) = 319 (1) [M+], 260 (40) [(C15H18NO3)

+], 232 (10), 186 (65)

[(C11H8NO2)+], 161 (20), 159 (25), 158 (100), 130 (15), 116 (15), 89 (15), 84 (20).

HRMS (EI) C17H21NO5: calc.: [M+]: 319.1414

found: [M+]: 319.1419.

Chiral HPLC: tR [racemate] = 8.56 min, 28.2 min; tR [ent-3e] = 8.91 min, tR [3e] = 27.9 min;

95% ee (AS-H, 250 × 4.6 mm, n-hexane/i-PrOH = 90:10, 1 mL/min, λ = 210 nm).


= −155 (c = 0.53, MeOH).

S17

(2aS,8bR)-1-((tert-Butyldimethylsilyl)oxy)-1-methoxy-3-oxo-1,3,4,8b-tetrahydrocyclo-

buta[c]quinolin-2a(2H)-yl acetate (3f)

Racemic procedure:

Using the general procedure a solution of quinolone 4 (170 mg, 837 µmol, 1.0 equiv.) and

tert-butyl-[(1-methoxyvinyl)oxy]-dimethylsilane 5f (3.40 mL, 16.7 mmol, 20 equiv.) in

acetonitrile (170 mL) was irradiated for three hours. Before purification the residual olefin

should be decomposed by addition of MeOH. Purification of the crude product by flash

column chromatography on silica (∅ 25 × 4 cm) eluting with EtOAc-pentane (1:4) gave the

title compound 3f (193 mg, 492 µmol, 59%) as colourless solid in a diastereomeric mixture

62:38 (by 1H-NMR spectroscopy).


Following the general procedure a solution of quinolone 4 (50.0 mg, 246 µmol, 1.0 equiv.),

template 6 (217 mg, 615 µmol, 2.5 equiv.) and tert-butyl-[(1-methoxyvinyl)oxy]-

dimethylsilane 5f (1.00 mL, 492 mmol, 20 equiv.) in toluene (50 mL) was irradiated for

twelve hours at −70 °C. Before purification the residual olefin should be decomposed with

MeOH. Purification of the crude product by flash column chromatography on silica

(∅ 20 × 2 cm) eluting with EtOAc-pentane (2:3) gave the title compound 3f (93.5 mg,

239 µmol, 97%) as colourless solid in a diastereomeric mixture 71:29 (by 1H-NMR

spectroscopy).

m.p.: 98 °C.


S18

IR (ATR): ν̃ =3214 (w, NH), 2956 (m), 2928 (m, CH), 1742 (m, C=O), 1671 (s), 1595 (w),

1492 (w), 1372 (w), 1241 (m, C−O), 1197 (w), 1132 (w), 1122 (w), 1093 (w), 1071 (m), 838

(m), 754 (m).

Major isomer:

1H-NMR (360 MHz, CDCl3): δ (ppm) = 0.18 [s, 3 H, Si(CH3)(CH3)], 0.20 [s, 3 H,

Si(CH3)(CH3)], 0.95 [s, 9 H, SiC(CH3)3], 2.09 (s, 3 H, H-2´), 2.87 (dd, 2J = 13.5 Hz,

4J = 2.2 Hz, 1 H, H-2

d), 2.93 (s, 3 H, OCH3) 3.06 (d,

2J = 13.5 Hz, 1 H, H-2

u), 3.82 (s, 1 H,

H-8b), 6.73 (d, 3J = 8.1 Hz, 1 H, H-5), 6.97-7.02 (m, 1 H, H-7), 7.11 (d,

3J = 7.7 Hz, 1 H,

H-8), 7.17-7.21 (m, 1 H, H-6), 7.80 (br s, 1 H, NH).

13C-NMR (63 MHz, CDCl3): δ (ppm) = −3.2 [q, Si(CH3)(CH3)], −2.9

[q, Si(CH3)(CH3)], 18.2 [s, SiC(CH3)3], 20.7 (q, C-2´), 25.8 [q, SiC(CH3)2], 47.6

(t, C-2), 50.2 (q, OCH3), 59.8 (d, C-8b), 68.9 (s, C-2a), 96.3 (s, C-1), 115.7 (d, C-5), 119.2 (s,

C-8a), 123.2 (d, C-7), 128.2 (d, C-6), 128.5 (d, C-8), 137.1 (s, C-4a), 168.1

(s, C-3), 170.5 (s, C-1´).

Minor isomer:

S19

13C-NMR (63 MHz, CDCl3): δ (ppm) = −3.6 [q, Si(CH3)(CH3)], −3.4

[q, Si(CH3)(CH3)], 17.8 [s, SiC(CH3)3], 20.7 (q, C-2´), 25.3 [q, SiC(CH3)3], 48.6

(t, C-2), 49.7 (q, OCH3), 56.7 (d, C-8b), 69.0 (s, C-2a), 96.4 (s, C-1), 115.6 (d, C-5), 119.4 (s,

C-8a), 123.3 (d, C-7), 127.7 (d, C-6), 129.1 (d, C-8), 136.8 (s, C-4a), 168.0 (s, C-3), 170.7 (s,

C-1´).

MS (EI, 70 eV): m/z (%) = 332 (100) [(M-OAc)+], 274 (30) [(C14H12NO5)

+], 216 (30), 185

(81), 158 (59) [(C9H4NO2)+], 129 (43), 89 (73), 75 (75), 43 (97) [(C2H3O)

+].

HRMS (EI): C18H26NO3Si calc.: [(M-OAc)+]: 332.1676

found: [(M-OAc)+]: 332.1673.

Chiral HPLC: tR [racemate] = 10.1 min, 12.1 min, 16.8 min, 22.4 min; tR [3f] = 10.1 min,

16.9 min, tR [ent-3f] = 12.1 min, 22.5 min; 88% ee, 95% ee, (AD-H, 250 × 4.6 mm, n-

hexane/i-PrOH = 90:10, 1 mL/min, λ = 210 nm, 254 nm).


= −136 (c = 0.48, CH2Cl2).

For product 3f different conditions were tested (chart 1).

chart 1: Dependence of temperature and solvent for yield, diastereomeric ratio and enantiomeric excess.

entry solvent temp [°C] yield [%] d.r. ee

1a tol r.t. 65 62:38 26%, 27%

2a tol − 74 62 69:31 88%, 89%

3b tol − 70 97 71:29 88%, 95%

4a PhCF3 − 20 58 70:30 56%, 60%

5a MeCN − 40 92 66:34 0%, 0%

6a THF − 70 52 57:43 2%, 6%

7a EtOAc − 70 72 58:42 17%, 18%

8a MeOH − 70 23 67:33 6%, 3%

a: reaction was performed for three hours at λ = 366 nm; b: reaction was performed for twelve hours at λ = 366 nm.

S20

(2aS,8bR)-1-((tert-Butyldimethylsilyl)oxy)-1-methoxy-4-methyl-3-oxo-1,3,4,8b-tetra-

hydrocyclobuta[c]quinolin-2a(2H)-yl acetate (9)

Racemic procedure:

Photoproduct 3f (555 mg, 1.42 mmol, 1.0 equiv.) was dissolved in THF (20 mL) and cooled

to 0 °C. At this temperature sodium hydride (62.3 mg, 60%, 1.55 mmol, 1.1 equiv.) was

added and the mixture was allowed to stir for 30 minutes. After that period of time methyl

iodide (0.44 mL, 1.02 g, 7.08 mmol, 5.0 equiv.) was added dropwise. The mixture was

allowed to warm up to room temperature over night. The solvent was removed under reduced

pressure. Purification by flash column chromatography on silica (∅ 30 × 4 cm) eluting with

EtOAc-pentane (1:9→1:1) gave the title compound 9 (425 mg, 1.05 mmol, 74%) as

colourless oil in a diastereomeric mixture 62:38 (by 1H-NMR spectroscopy).


In analogue way photoproduct 3f of enantioselective photoreaction was realized in a scale of

761 µmol. So quinolone 9 (167 mg, 412 µmol, 54%) was isolated as colourless oil in a

diastereomeric mixture 74:26 (by 1H-NMR spectroscopy).


IR (ATR): ν̃ = 2953 (m, C-H), 2854 (w, C-H), 1735 (s, C=O), 1644 (br, C=O), 1599 (m),

1472 (m), 1372 (w), 1230 (br, C−O), 759 (m).

S21

Major isomer:

1H-NMR (250 MHz, CDCl3): δ (ppm) = 0.17 [s, 3 H, Si(CH3)(CH3)], 0.18 [s, 3 H,

Si(CH3)(CH3)], 0.95 [s, 9H, Si(CH3)3], 2.05 (s, 3 H, H-2´), 2.88 (s, 3 H, OCH3), 2.89 (d,

2J = 2.1 Hz, 1 H, H-2

u), 3.02 (d,

4J = 13.7 Hz, 1 H, H-2

d), 3.40 (s, 3 H, NCH3), 3.78 (s, 1 H,

H-8b), 6.96-7.00 (m, 1 H, H-5), 7.01-7.05 (m, 1 H, H-7), 7.11 (dd, 3J = 7.4 Hz,

4J = 1.7 Hz, 1

H, H-8), 7.23-7.31 (m, 1 H, H-6).

13C-NMR (63 MHz, CDCl3): δ (ppm) = −3.2 [q, Si(CH3)(CH3)], −3.0 [q, C-Si(CH3)(CH3)],

18.2 [s, SiC(CH3)3], 20.7 (q, C-2´), 25.8 [q, SiC(CH3)3], 30.1 (q, NCH3), 48.2 (t, C-2), 50.3

(q, OCH3), 59.1 (d, C-8b), 68.6 (s, C-2a), 96.0 (s, C-1), 114.8 (d, C-5), 120.5 (s, C-8a), 123.1

(d, C-7), 128.2 (d, C-6), 128.5 (d, C-8), 140.2 (s, C-4a), 167.7 (s, C-3), 170.5 (s, C-1´).

Minor isomer:

u

d1

3

4a

7 1´8b

N O

H

O

O OTBS

O

H

H

13C-NMR (63 MHz, CDCl3): δ (ppm) = −3.6 [q, Si(CH3)(CH3)], −3.5 [q, Si(CH3)(CH3)], 17.8

[s, SiC(CH3)3], 20.7 (q, C-2´), 25.3 [q, SiC(CH3)3], 30.0 (q, NCH3), 49.1 (t, C-2), 49.8 (q,

OCH3), 56.1 (d, C-8b), 68.5 (s, C-2a), 96.0 (s, C-1), 114.7 (d, C-5), 120.6 (s, C-8a), 123.1 (d,

C-7), 127.6 (d, C-6), 129.0 (d,C-8), 139.8 (s, C-4a), 167.6 (s, C-3), 170.7 (s, C-1´).

S22

MS (EI, 70 eV): m/z (%) = 346 (100) [(M-C2H3O2)+], 231 (57), 216 (52) [(C12H10NO3)

3+],

200 (66) [(C12H10NO2)2+

], 199 (77), 175 (54), 172 (96), 89 (44), 75 (66), 73 (36), 57 (20), 44

(36).

HRMS (EI): C19H28O3NSi calc.: [(M-OAc)+]: 346.1833

found: [(M-OAc)+]: 346.1836.


= −146 (c = 0.64, CH2Cl2).

(2aS,8bR)-1-((tert-Butyldimethylsilyl)oxy)-2a-hydroxy-1-methoxy-4-methyl-2,2a,4,8b-

tetrahydrocyclobuta[c]quinolin-3(1H)-one (10)

Racemic procedure:

Quinolone 9 (458 mg, 1.13 mmol 1.0 equiv.) was dissolved in ethanol (38 mL) and potassium

cyanide (36.7 mg, 569 µmol, 0.5 equiv.) was added. The mixture was stirred for six hours at

80 °C. The solvent was removed under reduced pressure. Purification of the crude product by

flash column chromatography on silica (∅ 25 × 3 cm) eluting with EtOAc-pentane (1:9→1:4)

gave the title compound 10 (398 mg, 1.10 mmol, 97%) as colourless oil in a diastereomeric

mixture 67:33 (by 1H-NMR spectroscopy).


In analogue way quinolone 9 was used as starting material in a scale of 354 µmol. On that

way quinolone 10 (129 mg, 354 µmol, quant.) was isolated as colourless oil in a

diastereomeric mixture 70:30 (by 1H-NMR spectroscopy).

S23

TLC: Rf = 0.63 (pentane-EtOAc = 1:1) [UV, CAM].

IR (ATR): ν̃ = 3372 (b, OH), 2926 (m, C-H), 1791 (m, C=O), 1733 (m), 1637 (s, C=O), 1597

(s), 1466 (m), 1383 (w), 1273 (w), 1247 (w, C−O), 1222 (w), 1207 (w), 754 (m).

Major isomer:

1H-NMR (500 MHz, CDCl3): δ (ppm) = 0.18 [s, 6 H, Si(CH3)2] 0.95 [s, 9 H, SiC(CH3)3],

2.58 (dd, 2J = 12.5 Hz,

4J = 1.6 Hz, 1 H, H-2

d), 2.88 (s, 3 H, NCH3), 3.02 (d,

2J = 12.5 Hz,

1 H, H-2u), 3.40 (s, 3 H, OCH3), 3.82 (s, 1 H, H-8b), 6.95-6.99 (m, 1 H, H-5), 7.00-7.05 (m,

1 H, H-7), 7.19 (dd, 3J = 7.5 Hz,

4J = 1.7 Hz, 1 H, H-8), 7.25-7.32 (m, 1 H, H-6).

13C-NMR (126 MHz, CDCl3): δ (ppm) = −3.1 [q, Si(CH3)(CH3)], −3.0 [q, Si(CH3) (CH3)],

18.2 [s, SiC(CH3)3], 25.8 [q, SiC(CH3)3], 29.9 (q, NCH3), 50.4 (q, OCH3), 50.6 (t, C-2), 57.6

(d, C-8b), 65.4 (s, C-2a), 95.5 (s, C-1), 114.8 (d, C-5), 119.9 (s, C-8a), 123.4 (d, C-7), 128.4

(d, C-6), 129.9 (d, C-8), 139.9 (s, C-4a), 171.2 (s, C-3).

Minor isomer:

u

d1

3

4a

7 8b

N O

H

OH

O OTBS

H

H

13C-NMR (126 MHz, CDCl3): δ (ppm) = −3.7 [q, Si(CH3)(CH3)], −3.5 [q, Si(CH3)(CH3)],

17.8 [s, SiC(CH3)3], 25.4 [q, SiC(CH3)3], 29.9 (q, NCH3), 50.0 (q, OCH3), 52.4 (t, C-2), 54.3

S24

(d, C-8b), 65.2 (s, C-2a), 96.4 (s, C-1), 114.6 (d, C-5), 120.2 (s, C-8a), 123.3 (d, C-7), 127.9

(d, C-6), 130.7 (d, C-8), 139.4 (s, C-4a), 171.2 (s, C-3).

MS (EI, 70 eV): m/z (%) = 232 (9) [(M-OTBDMS)+], 231 (19), 216 (23) [(C13H13NO2)

+], 175

(100) [(C10H9NO2)2+

], 172 (13), 147 (26), 118 (9), 89 (6), 77 (6).

HRMS (EI): C13H13NO3 calc.: [(M-C6H16OSi)+]: 231.0895

found: [(M-C6H16OSi)+]: 231.0890.

Chiral HPLC: tR [racemate] = 9.14 min, 10.1 min, 22.0 min, 39.9 min; tR [ent-10] =

9.07 min, 39.8 min, tR [10] = 9.88 min, 21.6 min; 93% ee, 85% ee (AD-H, 250 × 4.6 mm, n-

hexane/i-PrOH = 90:10, 1 mL/min, λ = 210 nm).


= −121 (c = 0.86, CH2Cl2).

(3aS,9bR)-3a-Hydroxy-5-methyl-3,3a,5,9b-tetrahydrofuro[3,2-c]quinoline-2,4-dione (2)

Racemic procedure:

Quinolone 10 (80.0 mg, 0.22 mmol, 1.0 equiv.) was dissolved in CH2Cl2 (6 mL) and cooled

down to 0 °C. At this temperature boron trifluoride diethyl etherate (27.8 µL, 31.2 mg,

0.22 mmol, 1.0 equiv.) was added dropwise. The mixture was stirred for 30 minutes and

afterwards meta-chloroperoxybencoic acid (59.7 mg, 70%, 0.24 mmol, 1.1 equiv.) was added.

The mixture was allowed to warm up to room temperature over night. The solvent was

removed under reduced pressure and purification by flash column chromatography on silica

S25

(∅ 20 × 3 cm) eluting with EtOAc-pentane (3:7) gave the title product 2 (38.9 mg,

0.17 mmol, 76%) as colourless solid.


In analogue way quinolone 10 was used as starting material in a scale of 0.22 mmol. Lactone

2 (58.2 mg, 250 µmol, 75%) was isolated as colourless solid. At this step the product was

purified by semipreparative HPLC (n-hexane/i-PrOH = 50:50, 15 mL/min, 70 min,

λ = 215 nm) to get a clean product with an enantiomeric excess of ≥ 99% ee.

m.p.: 191 °C.

TLC: Rf = 0.28 (pentane-EtOAc = 1:1) [UV, CAM].

IR (ATR): ν̃ = 3351 (b, OH), 3075 (w), 2925 (w, C-H), 1785 (s, C=O), 1644 (s, C=O), 1600

(s), 1469 (m), 1382 (m), 1167 (m, C−O), 1085 (m), 1001 (m), 761 (m).

1H-NMR (360 MHz, CDCl3): δ (ppm) = 2.68 (dd,

2J = 17.2 Hz,

4J = 1.2 Hz, 1 H, H-3

d), 2.76

(d, 2J = 17.2 Hz, 1 H, H-3

u), 3.47 (s, 3 H, NCH3), 4.26 (s, 1 H, OH), 5.69 (d,

4J = 1.2 Hz, 1 H,

H-9b), 7.07 (d, 3J = 7.5 Hz, 1 H, H-6), 7.21-7.23 (m, 1 H, H-8), 7.43 (td,

3J = 7.5 Hz,

4J = 0.7 Hz, 1 H, H-7), 7.54 (d,

3J = 7.5 Hz, 1 H, H-9).

13C-NMR (91 MHz, CDCl3): δ (ppm) = 30.5 (q, NCH3), 41.5 (t, C-3), 74.9 (s, C-3a), 82.3 (d,

C-9b), 115.2 (d, C-6), 121.0 (s, C-9a), 125.1 (d, C-8), 129.5 (d, C-9), 130.9 (d, C-7), 136.7 (s,

C-5a), 168.4 (s, C-4), 172.8 (s, C-2).

MS (EI, 70eV): m/z (%) = 233 (25) [M+], 215 (9), 187 (6) [(C11H9NO2)

+], 160 (8), 146 (12)

[(C9H8NO)2+

], 70 (11), 61 (14), 45 (12), 43 (100) [(CO2)2+

].

S26


found: [M+]: 233.0683.

Chiral HPLC: tR [racemate] = 6.90 min, 9.60 min; tR [ent-2] = 9.60 min, tR [2] = 6.91 min,

87% ee (AD-H, 250 × 4.6 mm, n-hexane/i-PrOH = 50:50, 1mL/min, λ = 210 nm).


= −137 (c = 0.36, CH2Cl2).

(3aS,9bR)-2,3a-Dihydroxy-5-methyl-3,3a,5,9b-tetrahydrofuro[3,2-c]quinolin-4(2H)-one

(11)

Racemic procedure:

Lactone 2 (40.0 mg, 172 µmol, 1.0 equiv.) was dissolved in CH2Cl2 (6 mL) and cooled down

to −78 °C. At this temperature di-iso-butylaluminium hydride (257 µL, 1 M in CH2Cl2,

257 µmol, 1.5 equiv.) was added dropwise. The mixture was stirred for one hour and

afterwards di-iso-butylaluminium hydride (257 µL, 1 M in CH2Cl2, 257 µmol, 1.5 equiv.) was

added again. After a further hour MeOH (4 mL) was added and the mixture was warmed to

room temperature. At room temperature saturated sodium-potassium-tartrate solution (6 mL)

was added and the mixture was stirred for one hour. Finally saturated sodium chloride

solution (6 mL) was added. The mixture was extracted with CH2Cl2 (4 × 10 mL). The

combined organic phases were dried over sodium sulfate and filtered. The solvent was

removed under reduced pressure. Purification by flash column chromatography on silica

(∅ 12 × 1.5 cm) with a dryload on celite eluting with EtOAc-pentane (3:7→1:1) gave the title

compound 11 (24.6 mg, 105 µmol, 61%) as colourless oil.

S27

Enantioselectiv procedure:

In analogue way lactone 2 was used as starting material in a scale of 126 µmol. Lactole 11

(17.9 mg, 75.9 µmol, 60%) was isolated as colourless oil.

TLC: Rf = 0.14 (P/EtOAc = 1/1) [UV, CAM].

IR (ATR): ν̃ = 3392 (b, OH), 2928 (m, C-H), 1662 (s, C=O), 1604 (s), 1475 (m),

1129 (w).

1H-NMR (360 MHz, CDCl3): δ (ppm) = 2.10-2.27 (m, 2H, H-3), 3.44 (s, 3H, H-NCH3), 4.12

(brs, 1H, H-=H), 4.46 (brs, 1H, H-OH), 5.41-5.44 (m, 2H, H-2, H-9b), 6.99

(dd, 3J = 7.7 Hz,

4J = 1.2 Hz, 1H, H-6), 7.17 (td,

3J = 7.7 Hz,

4J = 1.2 Hz, 1H, H-8), 7.34 (td,

3J = 7.7 Hz,

4J = 1.5 Hz, 1H. H-7), 7.56 (dd,

3J = 7.7 Hz,

4J = 1.5 Hz, 1H, H-9).

13C-NMR (91 MHz, CDCl3): δ (ppm) = 30.3 (q, NCH3), 45.6 (t, C-3), 77.8 (d, C-9b), 81.2 (s,

C-3a), 98.4 (d, C-2), 114.6 (d, C-6), 124.6 (s, C-9a), 125.1 (d, C-8), 128.7

(d, C-9), 129.5 (d, C-7), 136.1 (s, C-5a), 170.3 (s, C-4).

MS (EI,70 eV): m/z (%) = 235 (6) [M+], 146 (6) [(C9H8NO)

2+] , 100 (13), 84 (95), 82 (26), 66

(100), 48 (13), 46 (20).


found: [M+]: 235.0839.

S28

(3S,4R)-3,4-Dihydroxy-1-methyl-3-(3-methylbut-2-en-1-yl)-3,4-dihydroquinolin-2(1H)-

one (1)

Racemic procedure:

In a first step triphenyl-iso-propylphosphoniumbromide (167 mg, 434 µmol, 10 equiv.) was

suspended in THF (4 mL) and n-butyllithium (0.17 mL, 2.5 M in hexane, 434 µmol,

10 equiv.) was added slowly and the mixture was stirred for 30 minutes. To that mixture

lactole 11 (10.2 mg, 43.4 µmol, 1.0 equiv.) dissolved in THF (4 mL) was added dropwise at

0 °C. The mixture was stirred for three hours and finally quenched by addition of EtOAc

(4 mL). The crude product was purified by flash column chromatography on silica

(∅ 20 × 1.5 cm) with a dryload on celite eluting with EtOAc-pentane (1:2). So natural

product 1 (5.67 mg, 21.7 µmol, 50%) was isolated as colourless oil.

In analogue way lactole 11 was used as starting material in a scale of 42.5 µmol. Natural

product 1 (6.00 mg, 23.0 µmol, 55%) was isolated as colourless oil.

TLC: Rf = 0.76 (EtOAc) [UV, CAM].

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IR (ATR): ν̃ = 3414 (b, OH), 2960 (m), 2924 (s, C-H), 2850 (m, C-H), 1665 (s, C=O), 1605

(m), 1469 (w), 1376 (w), 1119 (m), 1045 (w), 756 (w).

1H-NMR (360 MHz, CDCl3): δ (ppm) = 1.41 (s, 3H, H-4´

*), 1.64 (s, 3H, H-5´

*), 1.98 (dd,

2J = 14.8 Hz,

3J = 7.3 Hz, 1H, H-1´β), 2.47 (dd,

2J = 14.8 Hz,

3J = 8.2 Hz, 1H, H-1´α), 2.69

(d, 3J = 3.4 Hz, 1H, 4-OH), 3.39 (s, 3H, NCH3), 3.92 (s, 1 H, 3-OH) 4.98-5.06 (m, 2H,H-2´,

H-4), 6.99 (d, 3J = 7.6 Hz, 1H, H-8), 7.19 (td,

3J = 7.6 Hz,

4J = 1.4 Hz, 1H, H-6), 7.34 (t,

3J = 7.6 Hz, 1H, H-7), 7.61 (dt,

3J = 7.6 Hz,

4J = 1.4 Hz, 1H, H-5).

13C-NMR (126 MHz, CDCl3): δ (ppm) = 17.8 (q, C-5´), 26.1 (q, C-4´), 28.8 (t, C-1´), 30.4 (q,

NCH3), 72.8 (d, C-4), 76.1 (s, C-3), 114.4 (d, C-8), 117.0 (d, C-2´), 124.3 (d, C-6), 125.1 (d,

C-5), 127.4 (s, C-4a), 128.7 (d, C-7), 136.5 (s, C-3´), 137.3 (s, C-8a), 172.3 (s, C-2).

* commutable signals.

MS (EI,70 eV): m/z (%) = 261 (4) [M+], 226 (66) [(C15H16NO)

2+], 192 (20)

[(M-C5H9)+], 176 (23), 175 (32), 174 (41) [(M-C5H10O)

+], 146 (58) [(M-C6H14O2)

+], 109 (45),

85 (43), 69 (55) [(C5H9)+], 57 (50), 55 (37), 43 (100) [(C3H6)

+].


found: [M+]: 261.1359.

Chiral HPLC: tR [racemate] = 11.2 min, 15.1 min; tR [ent-1] = 11.1 min, tR [1] = 15.0 min;



= −6.34 (c = 0.16, CHCl3).

The analytical data are in agreement with the literature (see next page).[3]

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Comparison of Analytical Data (natural product/synthetic material)

chart 2: Comparison between literature data and measured data for 1H-NMR in CDCl3.

1H assignment natural product

[3] [ppm] synthetic material [ppm]

H-5 7.61 (d, J = 7.7 Hz) 7.61 (dt, J = 7.6, 1.4 Hz)

H-7 7.34 (t, J = 7.7 Hz) 7.34 (t, J = 7.6 Hz)

H-6 7.19 (t, J = 7.7 Hz) 7.19 (td, J = 7.6, 1.4 Hz)

H-8 6.99 (d, J = 7.7 Hz) 6.99 (d, J = 7.6 Hz)

H-2´ 5.03 (overlapped with H-4) 4.98-5.06 (m, H-2´, H-4)

H-4 5.01 (overlapped with H-2´) 4.98-5.06 (m, H-2´, H-4)

3-OH 3.93 (br s) 3.92 (s)

N-CH3 3.39 (s) 3.39 (s)

4-OH 2.70 (br s) 2.69 (d, J = 3.4 Hz)

H-1´ 2.47 (dd, J = 14.7, 8.1 Hz) 2.47 (dd, J = 14.8, 8.2 Hz, H-1α´)

H-1´ 1.98 (dd, J = 14.7, 7.3 Hz) 1.98 (dd, J = 14.8, 7.3 Hz, H-1β´)

3´-CH3 1.64 (s) 1.64 (s)

3´-CH3 1.41 (s) 1.41 (s)

chart 3: Comparison between literature data and measured data for 13C-NMR in CDCl3.

13C assignment natural product


C-2 172.2 (s) 172.3 (s)

C-8a 137.2 (s) 137.3 (s)

C-3´ 136.2 (s) 136.5 (s)

C-7 128.5 (d) 128.7 (d)

C-4a 127.3 (s) 127.4 (s)

C-5 125.0 (d) 125.1 (d)

C-6 124.2 (d) 124.3 (d)

C-2´ 116.9 (d) 117.0 (d)

C-8 114.2 (d) 114.4 (d)

C-3 75.9 (s) 76.1 (s)

C-4 72.7 (d) 72.8 (d)

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N-CH3 30.2 (q) 30.4 (q)

C-1´ 28.7 (t) 28.8 (t)

3´-CH3 25.9 (q) 26.1 (q, C-4´)

3´-CH3 17.6 (q) 17.8 (q, C-5´)

chart 4: Comparison between literature data and synthetic data for 1H-NMR in DMSO-d6.

1H assignment natural product


H-5 7.38 (d, J = 7.8 Hz) 7.39 (d, J = 7.7 Hz)

H-7 7.28 (t, J = 7.8 Hz) 7.29 (td, J = 7.7, 1.6 Hz)

H-8 7.06 (d, J = 7.8 Hz) 7.06 (d, J = 7.7 Hz)

H-6 7.05 (t, J = 7.8 Hz) 7.07 (t, J = 7.7 Hz)

4-OH 5.65 (d, J = 4.8 Hz) 5.68 (d, J = 4.7 Hz)

3-OH 5.15 (br s) 5.20 (s)

H-2´ 5.04 (br t, J = 7.7 Hz) 5.06 (t, J = 7.4 Hz)

H-4 4.54 (d, J = 4.8 Hz) 4.55 (d, J = 4.7 Hz)

N-CH3 3.30 (s) 3.24 (s)

H-1´ 2.30 (dd, J = 15.0, 7.7 Hz) 2.32 (dd, J = 14.9, 7.4 Hz)

H-1´ 2.15 (dd, J = 15.0, 7.7 Hz) 2.16 (dd, J = 14.9, 7.4 Hz)

3´-CH3 1.55 (s) 1.56 (s)

3´-CH3 1.37 (s) 1.38 (s)

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2. References for the Supporting Information

1. F. Marsais, A. Godard, G. Queguiner, Journal of Heterocyclic Chemistry 1989, 26,

1589-1594.

2. K. Kobayashi, M. Suzuki, H. Suginome, The Journal of Organic Chemistry 1992, 57,

599-606.

3. C. Ito, M. Itoigawa, T. Otsuka, H. Tokuda, H. Nishino, H. Furukawa, Journal of

Natural Products 2000, 63, 1344-1348.

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3. NMR spectra of new compounds

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4. HPLC traces of racemic and enantioenriched products

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Enantioselective, intermolecular [2+2] photocycloaddition ... · Enantioselective, intermolecular [2+2] photocycloaddition reactions of 3-acetoxyquinolone: Total synthesis of (−−−−)-pinolinone