Synthesis of Unique Analogues of the Ergoline Skeleton Using Intramolecular [3+2] Cycloaddition

Sébastien Picard; Frédéric Lecornué; Georges Bashiardes

doi:10.1055/s-0033-1341053

Synlett, Inhaltsverzeichnis

Synlett 2014; 25(08): 1106-1110
DOI: 10.1055/s-0033-1341053

letter

Synthesis of Unique Analogues of the Ergoline Skeleton Using Intramolecular [3+2] Cycloaddition

Sébastien Picard

Organic Synthesis Group, Institut de Chimie des Milieux et des Matériaux de Poitiers, UMR-CNRS 7285, TSA 51106, Université de Poitiers, 4 Rue Michel Brunet, Bât B28, 86073 Poitiers Cedex 9, France Fax: +33(5)49453501 eMail: frederic.lecornue@univ-poitiers.fr eMail: gbashiardes@hotmail.com

,

Frédéric Lecornué*

Organic Synthesis Group, Institut de Chimie des Milieux et des Matériaux de Poitiers, UMR-CNRS 7285, TSA 51106, Université de Poitiers, 4 Rue Michel Brunet, Bât B28, 86073 Poitiers Cedex 9, France Fax: +33(5)49453501 eMail: frederic.lecornue@univ-poitiers.fr eMail: gbashiardes@hotmail.com

,

Georges Bashiardes*

Organic Synthesis Group, Institut de Chimie des Milieux et des Matériaux de Poitiers, UMR-CNRS 7285, TSA 51106, Université de Poitiers, 4 Rue Michel Brunet, Bât B28, 86073 Poitiers Cedex 9, France Fax: +33(5)49453501 eMail: frederic.lecornue@univ-poitiers.fr eMail: gbashiardes@hotmail.com

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Abstract

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Abstract

A new methodology is described for the novel and rapid synthesis of unique analogues of the ergoline structure. After introduction of an allyl or alkynyl group in position C-4 on indole-3-carboxaldehyde, an intramolecular 1,3-dipolar cycloaddition using α-amino esters, directly provides novel ergoline-type compounds in good yields.

Key words

intramolecular 1,3-dipolar cycloaddition - Stille reaction - Sonogashira reaction - microwave - ergoline

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Referenzen

References and Notes

1a Ninomiya I, Kigushi T In The Alkaloids: Chemistry and Pharmacology . Vol. 38. Brossi A. Academic Press; San Diego: 1990: 1
1b Stadler PA, Floss HG In Natural Products and Drugs Development . Krogsgaard-Larsen P, Christensen SB, Kofod H. Munksgaard; Copenhagen: 1984: 467

2 Lieberman AN, Leibowitz M, Neophytides A, Kupersmith M, Mehl S, Kleinberg D, Serby M, Goldstein M. Lancet 1979; 314: 1129
3 Somei M, Yokoyama Y, Murakami Y In The Alkaloids . Vol. 54. Academic Press; San Diego: 2000: 191
4 Hollins RA, Colnago LA, Salim VM, Seidl MC. J. Heterocycl. Chem. 1979; 16: 993
5 General Procedure for the Synthesis of 7a,b: Under a nitrogen atmosphere, a solution of indole-3-carboxaldehyde (6a) or 2-methylindole-3-carboxaldehyde (6b; 1 mmol) and thallium trifluoroacetate (1.2 mmol) in trifluoroacetic acid (2 mL/mmol) was stirred overnight at r.t. and the solvent was then removed under reduced pressure. The residue was dissolved in H₂O (4 mL/mmol) and then KI (4 mmol) was added. The reaction mixture was stirred for 4 h at r.t., quenched with aq sat. Na₂S₂O₃ and then extracted several times with EtOAc. The combined organic layers were washed with brine, dried over MgSO₄, filtered and concentrated under reduced pressure. The residue was dissolved in anhyd THF (10 mL/mmol), and then DMAP (1.5 mmol) was added, followed by the addition of Boc₂O (2 mmol). The reaction mixture was stirred for 2 h at r.t., quenched with an aq sat. NH₄Cl solution, and then extracted with Et₂O several times. The combined organic layers were washed with brine, dried over MgSO₄, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography on silica, eluting with pentane–EtOAc (95:5), to give 7a,b. 1-(tert-Butoxycarbonyl)-4-iodoindole-3-carboxaldehyde (7a): 93% yield; white powder; mp 108 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.67 (s, 9 H), 7.08 (t, J = 8.0 Hz, 1 H), 7.82 (d, J = 8.0 Hz, 1 H), 8.32 (d, J = 8.0 Hz, 1 H), 8.38 (s, 1 H), 11.22 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 28.0, 83.1, 86.0, 115.4, 120.7, 126.2, 130.2, 132.3, 135.6, 136.9, 148.0, 185.8. IR: 3155, 3055, 1752, 1670, 1253, 1149 cm^–1. MS (EI): m/z (%) = 372.1 (47) [MH]⁺, 338.7 (61), 272.4 (100), 214.4 (48). 1-(tert-Butoxycarbonyl)-4-iodo-2-methylindole-3-carboxadehyde (7b): yield: 74%; white powder; mp 109 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.67 (s, 9 H), 2.91 (s, 3 H), 6.97 (t, J = 8.1 Hz, 1 H), 7.78 (d, J = 8.1 Hz, 1 H), 8.14 (d, J = 8.1 Hz, 1 H), 11.22 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 15.2, 28.1, 81.8, 86.2, 115.0, 117.5, 125.3, 129.8, 135.8, 136.3, 146.1, 149.1, 187.7. IR: 3136, 3054, 1751, 1665, 1254, 1139 cm^–1. HMRS (EI): m/z calcd for C₁₅H₁₆INO₃Na: 408.00727; found: 408.00846.

6a Milstein D, Stille JK. J. Am. Chem. Soc. 1978; 100: 3636
6b For a review of the Stille reaction, see: Heravi MM, Hashemi E, Azimian F. Tetrahedron 2014; 70: 7

7 Tidwell JH, Peat AJ, Buchwald SL. J. Org. Chem. 1994; 59: 7164
8 General Procedure for the Synthesis of 8 and 9: Under a nitrogen atmosphere, a solution of 7 (1 mmol), tetrakis(triphenylphosphine)palladium (0.05 mmol) and allyltributylstannane or tributylvinylstannane (1.1 mmol) in anhyd THF (10 mL/mmol) was heated overnight at reflux. The reaction mixture was quenched with brine and then extracted several times with Et₂O. The combined organic layers were dried over MgSO₄, filtered and concentrated under reduced pressure. The crude product was purified by chromatography on silica, eluting with pentane–EtOAc (90:10). 1-(tert-Butoxycarbonyl)-4-vinylindole-3-carboxaldehyde (8): 94% yield; white powder; mp 90 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.70 (s, 9 H), 5.42 (d, J = 10.9 Hz, 1 H), 5.75 (d, J = 17.3 Hz, 1 H), 7.37 (t, J = 7.9 Hz, 1 H), 7.54 (d, J = 7.9 Hz, 1 H), 7.94 (dd, J = 17.3, 10.9 Hz, 1 H), 8.14 (d, J = 7.9 Hz, 1 H), 8.27 (s, 1 H), 10.05 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 28.0, 85.7, 114.4, 115.6, 121.4, 123.0, 123.9, 125.9, 133.0, 136.7, 137.0, 138.6, 148.4, 184.9. IR: 3127, 3092, 1753, 1686, 1255, 1152, 996, 908 cm^–1. HMRS (EI): m/z calcd for C₁₆H₁₇NO₃Na: 294.11061; found: 294.11092. 1-(tert-Butoxycarbonyl)-4-allylindole-3-carboxaldehyde (9a): 87% yield; white powder; mp 91 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.70 (s, 9 H), 4.01 (d, J = 6.0 Hz, 2 H), 4.91 (dd, J = 17.1, 1.7 Hz, 1 H), 5.04 (dd, J = 10.2, 1.7 Hz, 1 H), 6.06 (ddt, J = 17.1, 10.2, 6.0 Hz, 1 H), 7.19 (d, J = 8.0 Hz, 1 H), 7.36 (t, J = 8.0 Hz, 1 H), 8.13 (d, J = 8.0 Hz, 1 H), 8.30 (s, 1 H), 10.08 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 28.1, 39.4, 85.6, 113.4, 115.6, 122.8, 125.1, 125.8, 126.0, 134.3, 137.0, 137.3, 137.5, 148.6, 185.4. IR: 3115, 3075, 1741, 1686, 1640, 1255, 1149, 1010, 918 cm^–1. HMRS (EI): m/z calcd for C₁₇H₁₉NO₃Na: 308.12626; found: 308.12584. 1-(tert-Butoxycarbonyl)-4-allyl-2-methylindole-3-carboxaldehyde (9b): 80% yield; white powder; mp 168 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.71 (s, 9 H), 2.94 (s, 3 H), 3.86 (d, J = 5.4 Hz, 2 H), 4.87 (dd, J = 17.2, 1.7 Hz, 1 H), 5.07 (dd, J = 10.2, 1.7 Hz, 1 H), 6.06 (ddt, J = 17.2, 10.2, 5.4 Hz, 1 H), 7.14 (d, J = 7.9 Hz, 1 H), 7.27 (t, J = 7.9 Hz, 1 H), 8.01 (d, J = 7.9 Hz, 1 H), 10.42 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 15.3, 28.6, 40.0, 86.1, 113.7, 116.6, 119.5, 125.0, 125.8, 126.5, 132.4, 136.6, 137.3, 147.3, 150.1, 188.6. IR: 3075, 3011, 1751, 1665, 1272, 1142, 1004, 927 cm^–1. MS (EI): m/z (%) = 300.0 (70) [MH]⁺, 251.7 (61), 200.4 (56), 176.6 (31), 143.3 (47), 122.8 (100).

9a Sonogashira K, Tohda Y, Hagihara N. Tetrahedron Lett. 1975; 4467
9b For a review on Sonogashira reaction, see: Chinchilla R, Nájera C. Chem. Rev. 2007; 107: 874

10 Miller MW, Johnson CR. J. Org. Chem. 1997; 62: 1582
11 1-(tert-Butoxycarbonyl)-4[(trimethylsilyl)ethynyl]-indole-3-carboxaldehyde (10): Under a nitrogen atmosphere, a solution of 1-(tert-butoxycarbonyl)-4-iodoindole-3-carboxaldehyde (7a; 1 mmol), dichlorobis(triphenylphosphine)palladium (0.05 mmol), copper(I) iodide (0.1 mmol) and trimethylsilylacetylene (1.2 mmol) in anhyd THF (10 mL/mmol) was stirred for 10 min at 0 °C and then Et₃N (3 mmol) was added dropwise. The reaction mixture was stirred for 2 h at r.t., quenched with an aq sat. NH₄Cl solution and then extracted with Et₂O. The organic layer was dried over MgSO₄, filtered and concentrated under reduced pressure. The crude mixture was purified by chromatography on silica, eluting with pentane–Et₂O (90:10), to give 10 in 96% yield as a white powder; mp 136 °C. ¹H NMR (300 MHz, CDCl₃): δ = 0.30 (s, 9 H), 1.68 (s, 9 H), 7.32 (t, J = 8.0 Hz, 1 H), 7.50 (dd, J = 8.0, 1.0 Hz, 1 H), 8.26 (dd, J = 8.0, 1.0 Hz, 1 H), 8.36 (s, 1 H), 10.99 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = –0.3, 28.0, 85.8, 99.4, 104.3, 114.6, 116.3, 121.4, 124.9, 127.7, 129.3, 130.8, 136.0, 148.6, 187.6. IR: 2151, 1749, 1676, 1252, 1149, 859 cm^–1. HMRS (EI): m/z calcd for C₁₉H₂₃NO₃NaSi: 364.13499; found: 364.13352.
12 General Procedure for the Synthesis of 11: Thermal Conditions: A solution of 8 or 9 (1 mmol) and α-amino ester 14 (2 mmol) in toluene (10 mL) was stirred and heated at reflux for 24 h. After evaporation of the solvent under reduced pressure, the crude product was purified by short column chromatography on silica. Microwave Conditions: In a pyrex tube (2 × 15 mm), 8 or 9 (1 mmol) and α-amino ester 14 (2 mmol) in toluene (0.5 mL) were submitted to microwave irradiation (CEM Discoverer apparatus; 100 W, 110 °C) for 5 min. After cooling, the crude product was purified by short column chromatography on silica gel. 1-(tert-Butoxycarbonyl)-8-methyl-9-methyl-6,6a,7,8,9a-pentahydro-9-azaindeno[4,5,6-cd]indole-2,8-dicarboxylate (11a): 95% yield (Δ) and 99% yield (MW); yellow oil as a mixture of two diastereomers which were separated by column chromatography. Major diastereomer: yellow oil. ¹H NMR (300 MHz, CDCl₃): δ = 1.68 (s, 9 H), 1.87–2.02 (m, 1 H), 2.13–2.25 (m, 1 H), 2.63 (s, 3 H), 2.81–2.91 (m, 2 H), 3.07 (dd, J = 18.2, 7.4 Hz, 1 H), 3.53 (dd, J = 9.8, 4.9 Hz, 1 H), 3.74 (s, 3 H), 4.35 (d, J = 4.3 Hz, 1 H), 6.98 (d, J = 8.0 Hz, 1 H), 7.24 (t, J = 8.0 Hz, 1 H), 7.53 (s, 1 H), 7.76 (d, J = 8.0 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 28.2, 30.2, 34.2, 36.2, 38.0, 51.6, 58.9, 63.7, 83.6, 112.6, 115.1, 120.4, 121.7, 125.1, 128.7, 129.4, 133.0, 150.2, 174.8. IR: 3019, 2980, 2951, 1735, 1718, 1439, 1370, 1301, 1281, 1256, 1216, 1149, 1120, 755, 667 cm^–1. HMRS (EI): m/z calcd for C₂₁H₂₆N₂O₄Na: 393.17903; found: 393.17895. Minor diastereomer: yellow oil. ¹H NMR (300 MHz, CDCl₃): δ = 1.66 (s, 9 H), 1.85–1.96 (m, 1 H), 2.17–2.32 (m, 1 H), 2.43–2.55 (m, 1 H), 2.73 (s, 3 H), 2.87 (dd, J = 15.7, 12.0 Hz, 1 H), 3.13 (dd, J = 15.7, 3.9 Hz, 1 H), 3.76 (s, 3 H), 3.99 (dd, J = 8.7, 2.0 Hz, 1 H), 4.02 (dd, J = 8.4, 6.5 Hz, 1 H), 7.00 (d, J = 8.0 Hz, 1 H), 7.24 (t, J = 8.0 Hz, 1 H), 7.45 (s, 1 H), 7.76 (d, J = 8.0 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 28.2, 32.5, 33.6, 37.3, 43.7, 51.7, 64.0, 65.7, 83.4, 112.9, 117.3, 119.4, 120.5, 125.2, 130.2, 132.0, 133.6, 150.2, 174.6. IR: 3016, 2980, 1740, 1702, 1458, 1440, 1370, 1240, 1216, 1153, 755, 666 cm^–1. HMRS (EI): m/z calcd for C₂₁H₂₆N₂O₄Na: 393.17903; found: 393.17801. 1-(tert-Butoxycarbonyl)-8-ethyl-9-benzyl-6,6a,7,8,9a-pentahydro-9-azaindeno[4,5,6-cd]indole-2,8-dicarboxylate (11b): 75% yield (Δ) and 90% yield (MW); viscous yellow oil as a single diastereomer. ¹H NMR (300 MHz, CDCl₃): δ = 1.18 (t, J = 7.1 Hz, 3 H), 1.68 (s, 9 H), 1.95–2.08 (m, 1 H), 2.10–2.20 (m, 1 H), 2.71–2.84 (m, 1 H), 2.90–3.00 (m, 2 H), 3.62 (dd, J = 9.3, 5.1 Hz, 1 H), 3.96 (d, J = 13.6 Hz, 1 H), 4.05 (q, J = 7.1 Hz, 2 H), 4.19 (d, J = 13.6 Hz, 1 H), 4.48 (d, J = 4.7 Hz, 1 H), 7.00 (d, J = 7.2 Hz, 1 H), 7.15–7.30 (m, 6 H), 7.53 (s, 1 H), 7.77 (d, J = 7.2 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.2, 28.3, 30.6, 34.5, 38.2, 52.3, 57.0, 60.3, 60.8, 83.6, 112.6, 116.1, 120.2, 122.3, 125.7, 126.9, 128.2, 128.5, 130.1, 133.1, 133.2, 139.3, 150.1, 174.8. IR: 3020, 2980, 1725, 1440, 1394, 1371, 1346, 1215, 1152, 1130, 756, 669 cm^–1. HMRS (EI): m/z calcd for C₂₈H₃₂N₂O₄Na: 483.22598; found: 483.22678. 2-(tert-Butoxycarbonyl)-7a-methyl-6a,9,10,11a-tetrahydro-6H-indolo[4,3-fg]pyrrolo-[1,2-a]indole-2,7a-dicarboxylate (11c): 97% yield (Δ) and 98% (MW); viscous oil, mixture of two inseparable diastereomers (ratio 60:40). ¹H NMR (300 MHz, CDCl₃): δ = 1.50–3.40 (m, 40 H), 3.78 (s, 6 H), 4.08 (d, J = 10.0 Hz, 1 H), 4.59 (d, J = 4.9 Hz, 1 H), 7.01 (d, J = 7.8 Hz, 2 H), 7.24 (t, J = 7.8 Hz, 2 H) 7.49 (s, 1 H), 7.69 (s, 1 H), 7.75–7.90 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 25.9, 26.7, 28.2, 31.5, 31.6, 37.6, 38.5, 39.7, 41.1, 42.1, 42.2, 51.2, 51.6, 52.5, 52.6, 57.3, 64.5, 76.1, 83.4, 83.6, 112.8, 113.0, 115.4, 117.7, 118.5, 120.3, 120.5, 122.6, 125.0, 125.2, 129.2, 129.9, 130.3, 131.6, 150.0, 177.1, 177.6. IR: 3020, 2980, 2952, 1727, 1439, 1386, 1371, 1297, 1281, 1215, 1152, 1132, 756, 669 cm^–1. HMRS (EI): m/z calcd for C₂₃H₂₈N₂O₄Na: 419.19468; found: 419.19534. 1-(tert-Butoxycarbonyl)-8-methyl-1,9-methyl-6,6a,7,8,9a-pentahydro-9-azaindeno[4,5,6-cd]indole-2,8-dicarboxylate (11d): 84% yield (Δ) and 97% yield (MW); viscous oil as a mixture of two diastereomers which were separated by column chromatography. Major diastereomer: viscous oil. ¹H NMR (300 MHz, CDCl₃): δ = 1.68 (s, 9 H), 2.07–2.16 (m, 1 H), 2.30–2.49 (m, 5 H), 2.62 (s, 3 H), 2.83 (d, J = 8.2 Hz, 2 H), 3.76 (s, 3 H), 4.03 (dd, J = 8.5, 5.6 Hz, 1 H), 4.21 (d, J = 4.1 Hz, 1 H), 6.94 (d, J = 8.0 Hz, 1 H), 7.14 (t, J = 8.0 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.6, 28.3, 31.9, 34.5, 34.8, 38.4, 51.3, 57.1, 63.2, 83.4, 113.1, 114.4, 119.9, 123.9, 127.4, 129.6, 134.1, 134.5, 151.1, 175.1. IR: 3021, 2980, 2950, 1728, 1454, 1370, 1328, 1215, 1145, 1102, 756, 668 cm^–1. HMRS (EI): m/z calcd for C₂₂H₂₈N₂O₄Na: 407.19468; found: 407.19663. Minor diastereoisomer: viscous oil. ¹H NMR (300 MHz, CDCl₃): δ = 1.66–1.80 (m, 10 H), 2.30–2.56 (m, 5 H), 2.67–2.80 (m, 4 H), 3.22 (dd, J = 15.6, 3.9 Hz, 1 H), 3.69 (dd, J = 8.8, 6.3 Hz, 1 H), 3.76 (s, 3 H), 3.95 (d, J = 10.8 Hz, 1 H), 6.97 (d, J = 8.0 Hz, 1 H), 7.15 (t, J = 8.0 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 16.1, 28.4, 32.0, 33.0, 39.3, 39.6, 52.1, 64.7, 68.5, 83.4, 113.4, 115.4, 120.4, 124.0, 129.2, 130.5, 130.6, 135.0, 151.0, 175.1. IR: 2980, 2929, 1734, 1446, 1370, 1327, 1214, 1146, 1098, 755, 668 cm^–1. HMRS (EI): m/z calcd for C₂₂H₂₈N₂O₄Na: 407.19468; found: 407.19622. 2-(tert-Butoxycarbonyl)-7a-methyl-1-methyl-6a,9,10,11a-tetrahydro-6H-indolo[4,3-f,g]pyrrolo-[1,2-a]indole-2,7a-dicarboxylate 11e: 90% yield (Δ) and 95% yield (MW); viscous oil, mixture of two inseparable diastereoisomers (ratio 80:20). ¹H NMR (300 MHz, CDCl₃): δ = 1.50–3.20 (m, 46 H), 3.78 (s, 6 H), 4.00 (dd, J = 11.5, 2.0 Hz, 1 H), 4.47 (d, J = 5.2 Hz, 1 H), 6.96 (d, J = 8.0 Hz, 2 H), 7.17 (t, J = 8.0 Hz, 2 H), 7.79 (d, J = 8.0 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.7, 14.9, 25.8, 26.4, 28.2, 28.3, 31.4, 32.5, 37.8, 38.5, 40.1, 41.1, 42.8, 43.1, 50.5, 52.2, 52.4, 57.5, 64.5, 71.9, 83.6, 84.7, 113.3, 113.4, 114.0, 120.1, 120.4, 123.7, 123.9, 124.9, 126.6, 128.6, 130.5, 133.8, 134.0, 134.5, 136.8, 150.0, 174.0. IR: 3020, 2980, 1729, 1442, 1385, 1374, 1296, 1281, 1213, 1151, 1132, 755, 670 cm^–1. HMRS (EI): m/z calcd for C₂₄H₃₀N₂O₄Na: 433.21033; found: 433.21232.
13 General Procedure for the Synthesis of 16: A solution of 10 (1 mmol), α-amino ester 14 (2 mmol) and sulfur (approx. 100 mg) in toluene (10 mL) was stirred and heated at reflux for 24 h. After evaporation of the solvent under reduced pressure, the crude product was purified by short column chromatography on silica gel. 2-tert-Butyl-7-methyl-6-(trimethylsilyl)-8-methylpentaleno[1,2,3-cd]indole-2,7-dicarboxylate (16a): 38% yield; white powder; mp 116 °C. ¹H NMR (300 MHz, CDCl₃): δ = 0.34 (s, 9 H), 1.64 (s, 9 H), 3.90 (s, 3 H), 4.03 (s, 3 H), 7.14 (s, 1 H), 7.21 (dd, J = 8.2, 7.7 Hz, 1 H), 7.32 (dd, J = 7.7, 1.0 Hz, 1 H), 7.98 (dd, J = 8.2, 1.0 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 0.3, 28.2, 38.2, 51.4, 86.1, 97.8, 104.0, 107.9, 114.8, 116.0, 125.7, 134.6, 143.1, 116.4, 117.4, 124.7, 126.3, 150.4, 162.2. IR: 1721, 1710, 1364, 1314, 1250, 1158, 1101, 842 cm^–1. MS (EI): m/z (%) = 425.0 (18) [MH]⁺, 370 (24), 369.0 (100), 337 (55), 325 (19), 143.1 (27) 122 (65). 2-tert-Butyl-7-ethyl-6-(trimethylsilyl)-8-benzylpentaleno[1,2,3-cd]indole-2,7-dicarboxylate (16b): 87% yield; white powder; mp 129 °C. ¹H NMR (300 MHz, CDCl₃): δ = 0.26 (s, 9 H), 1.24 (t, J = 7.1 Hz, 3 H), 1.64 (s, 9 H), 4.27 (q, J = 7.1 Hz, 2 H), 5.56 (s, 2 H), 7.15–7.35 (m, 8 H), 7.98 (d, J = 8.2 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 0.1, 14.3, 28.2, 53.5, 60.4, 83.4, 97.8, 103.8, 107.9, 114.7, 116.2, 125.6, 133.7, 142.9, 115.9, 124.6, 126.1, 127.3, 127.7, 128.7, 116.4, 137.7, 150.1, 161.8. IR: 2973, 2143, 1731, 1715, 1434, 1394, 1366, 1336, 1315, 1265, 1156, 1102, 842 cm^–1. HMRS (EI): m/z calcd for C₃₀H₃₄N₂O₄NaSi: 537.21856; found: 537.21889.
14 Bashiardes G, Safir I, Mohamed AS, Barbot F, Laduranty J. Org. Lett. 2003; 5: 4915