S. Muthusamy, B. Gnanaprakasam / Tetrahedron Letters 49 (2008) 475–480
479
Synlett 2005, 2611–2614; (g) Bradshaw, J. S.; Maas, G. E.; Izatt, R.
M.; Christensen, J. J. Chem. Rev. 1979, 79, 37–52; (h) Masamune, S.;
Bates, S. G.; Corcoran, J. W. Angew. Chem., Int. Ed. Engl. 1977, 16,
585–607. and references cited therein.
13. General procedure for the synthesis of bis-indol-3-yl crown compounds
8: To an oven-dried flask, 1,10-butane-1,4-diylbis(1H-indole) or 1,10-
hexane-1,6-diylbis(1H-indole) (0.3 mmol) and 2 mol % of rhodium(II)
acetate in dry benzene or DCM (100 mL) were charged under an inert
atmosphere and refluxed. To the above refluxing mixture, macrocyclic
diazocarbonyl compound 4 (0.75 mmol) in dry benzene or DCM was
added slowly over 1 h using a syringe pump and the mixture refluxed
for 6 h. Progress of the reaction was monitored by TLC. The solvent
was removed under reduced pressure and the resulting residue was
purified using 100–200 mesh silica gel column chromatography
(hexane/EtOAc) to afford the respective bis C–H insertion products
8. Bis-indol-3-yl macrocyclic dilactones 8a: White solid; mp 128–
132 °C; mmax (KBr)/cmꢁ1 2928, 2879, 1739, 1468, 1353, 1291, 1220,
1140, 754. 1H NMR (CDCl3, 200 MHz) d 7.68–7.64 (d, 2H, Arom-H,
J = 4 Hz), 7.30–7.12 (m, 8H, Arom-H), 5.02 (s, 2H, CH), 4.51–4.41
(m, 4H, OCH2), 4.20–4.03 (m, 8H, OCH2 and NCH2), 3.76–3.69 (m,
24H, OCH2), 1.84 (t, 4H, CH2). 13C NMR (CDCl3, 50.3 MHz) d 168.3
(C@O), 135.8 (quat-C), 127.8 (@CH), 127.1 (quat-C), 121.8 (@CH),
119.6 (@CH), 119.4 (@CH), 109.4 (@CH), 105.8 (quat-C), 70.6
(OCH2), 70.3 (OCH2), 68.7 (OCH2), 64.6 (OCH2), 49.5 (CH), 45.9
(NCH2), 27.5 (CH2). HRMS (ESI+) calcd for C42H53N2O14Na
(M + H + Na)+: 832.3395, found 832.3331. Bis-indol-3-yl macrocyclic
dilactones 8b: White solid; mp 168–170 °C; mmax (KBr)/cmꢁ1 3050,
2930, 2876, 1734, 1466, 1274, 1248, 1222, 1132, 743. 1H NMR
(CDCl3, 200 MHz) d 7.66–7.61 (m, 2H, Arom-H), 7.58–7.00 (m, 8H,
Arom-H), 5.03 (s, 2H, CH), 4.53–3.98 (m, 12H, OCH2 and NCH2),
3.78–3.61 (m, 24H, OCH2), 1.80–1.74 (m, 4H, CH2), 1.31–1.25 (m,
4H, CH2). 13C NMR (CDCl3, 50.3 MHz) d 168.4 (C@O), 135.8 (quat-
C), 127.8 (@CH), 127.2 (quat-C), 121.7 (@CH), 119.5 (@CH), 119.4
(@CH), 109.2 (@CH), 105.7 (quat-C), 70.6 (OCH2), 70.4 (OCH2),
68.7 (OCH2), 64.6 (OCH2), 49.4 (CH), 46.0 (NCH2), 29.8 (CH2), 26.3
(CH2). HRMS (ESI+) calcd for C44H56N2O14Na (M+Na)+: 859.3629,
found 859.3588.
14. General procedure for the synthesis of bis(indol-3-yl) macrocyclic
tetralactones 9: To an oven-dried flask, bis-diazocarbonyl compound
5 (0.3 mmol) and substituted indole (0.7 mmol) in dry benzene or
DCM (100 mL) were charged under an inert atmosphere. To the
above reaction mixture, 2 mol % of rhodium(II) acetate was added
and the mixture refluxed for 6 h. Progress of the reaction was
monitored by TLC. The solvent was removed under reduced pressure
and the resulting residue purified using 100–200 mesh silica gel
column chromatography (hexane/EtOAc) to afford the respective
bis(indol-3-yl) macrocyclic tetralactones 9. 12,25-Bis-(1-methyl-1H-
indol-3-yl)-1,4,7,10,14,17,20,23-octaoxacyclohexacosane-11,13,24,26-
tetraone 9a: Brown thick oil; mmax (neat)/cmꢁ1 3057, 2946, 2874, 1746,
1471, 1333, 1142, 735. 1H NMR (CDCl3, 200 MHz) d 7.61 (d, 2H,
Arom-H, J = 8 Hz), 7.25–7.10 (m, 8H, Arom-H), 5.00 (s, 2H, CH),
4.28 (m, 8H, OCH2), 3.71–3.62 (m, 16H, OCH2), 3.52 (s, 6H, NCH3).
13C NMR (CD3OD, 50.3 MHz) d 169.0 (C@O), 137.3 (quat-C), 129.3
(quat-C), 127.5 (@CH), 122.4 (@CH), 120.1 (@CH), 119.7 (@CH),
109.9 (quat-C), 70.9 (OCH2), 69.3 (OCH2), 65.3 (OCH2), 49.9 (CH),
33.3 (NCH3). HRMS (ESI+) calcd for C36H42N2O12Na (M+Na)+:
717.2635, found 717.2702.
6. Julian, R. R.; May, J. A.; Stoltz, B. M.; Beauchamp, J. L. Angew.
Chem., Int. Ed. 2003, 42, 1012–1015.
7. Bogdanova, A.; Perkovic, M. W.; Popik, V. V. J. Org. Chem. 2005,
70, 9867–9873.
8. (a) Muthusamy, S.; Gnanaprakasam, B.; Suresh, E. Org. Lett. 2006,
9, 1913–1916; (b) Muthusamy, S.; Gnanaprakasam, B.; Suresh, E. J.
Org. Chem. 2007, 72, 1495–1498; (c) Muthusamy, S.; Gnanapraka-
sam, B. Tetrahedron 2007, 63, 3355–3362.
9. Muthusamy, S.; Gnanaprakasam, B. Tetrahedron Lett. 2007, 48,
6821–6824.
10. General procedure for the synthesis of macrocyclic diazocarbonyl
compounds 4: To a solution containing macrocyclic dilactone 1
(1 mmol) and 4-acetamidobenzenesulfonyl azide (1.2 mmol) in dry
dichloromethane (50 mL) was added DBU (1.5 mmol) under an argon
atmosphere and the reaction stirred at room temperature over-
night. To the reaction mixture, water (150 mL) was added and the
aqueous extracted with DCM (3 ꢀ 100 mL). The organic layers
were combined, washed with water (2 ꢀ 200 mL) and dried over
anhydrous Na2SO4. The solvent was removed under reduced pressure
at room temperature and the residue subjected to short silica gel
column chromatography to obtain the respective pure diazo
ketones 4.
11. General procedure for the synthesis of macrocyclic diazocarbonyl
compounds 5: To a solution containing macrocyclic tetralactone 2
(0.5 mmol) and 4-acetamidobenzenesulfonyl azide (1.25 mmol) in dry
dichloromethane (100 mL) was added DBU (1.5 mmol) under an
argon atmosphere and the reaction stirred at room temperature
overnight. Water (150 mL) was added and the aqueous extracted with
DCM (3 ꢀ 100 mL). The combined organic layers were washed with
water (2 ꢀ 200 mL) and dried over anhydrous Na2SO4. The solvent
was removed under reduced pressure at room temperature and the
residue subjected to short silica gel column chromatography to afford
the respective pure macrocyclic diazocarbonyl compounds 5.
12. General procedure for the synthesis of indol-3-yl macrocyclic dilactones
7: To an oven-dried flask, macrocyclic diazocarbonyl compound 4
(0.5 mmol) and substituted indole (0.6 mmol) in dry benzene or DCM
(50 mL) were added under an inert atmosphere. To the above reaction
mixture, 2 mol % of rhodium(II) acetate was added and the mixture
refluxed for 4 h. Progress of the reaction was monitored by TLC. On
completion, the solvent was removed under reduced pressure and the
resulting residue purified using 100–200 mesh silica gel column
chromatography (hexane/EtOAc) to afford the respective indol-3-yl
macrocyclic dilactones 7. Selected spectral data. 15-(1H-Indol-3-yl)-
1,4,7,10,13-pentaoxacyclohexadecane-14,16-dione 7a: White solid; mp
105–108 °C; mmax (KBr)/cmꢁ1 3383, 3264, 2873, 1748, 1458, 1289,
1251, 1132, 1106, 741. 1H NMR (CDCl3, 200 MHz) d 8.75 (s, 1H,
NH), 7.64 (d, 1H, Arom-H, J = 2 Hz), 7.59–7.07 (m, 4H, Arom-H),
5.01 (s, 1H, CH), 4.52–4.03 (m, 4H, OCH2), 3.76–3.69 (m, 12H,
OCH2). 13C NMR (CDCl3, 50.3 MHz) d 168.5 (C@O), 135.9 (quat-
C), 124.7 (@CH), 122.0 (@CH), 119.8 (@CH), 119.1 (@CH), 111.4
(@CH), 106.7 (quat-C), 103.4 (quat-C), 70.5 (OCH2), 70.3 (OCH2),
68.7 (OCH2), 64.6 (OCH2), 49.6 (CH). HRMS (ESI+) calcd for
C19H23NO7Na (M+Na)+: 400.1372, found 400.1381. 15-(1-Methyl-
1H-indol-3-yl)-1,4,7,10,13-pentaoxacyclohexadecane-14,16-dione 7e:
White solid; mp 91–93 °C; mmax (KBr)/cmꢁ1 3053, 2910, 2875, 1724,
1475, 1277, 1255, 1221, 1142, 1117, 1107, 749. 1H NMR (CDCl3,
200 MHz) d 7.66 (d, 1H, Arom-H, J = 4 Hz), 7.30–7.12 (m, 4H,
Arom-H), 5.03 (s, 1H, CH), 4.53–4.42 (m, 2H, OCH2), 4.21–4.12 (m,
2H, OCH2), 3.76–3.59 (m, 15H, OCH2 and NCH3). 13C NMR
(CDCl3, 50.3 MHz) d 168.3 (C@O), 136.6 (quat-C), 128.7 (@CH),
126.9 (quat-C), 121.7 (@CH), 119.4 (@CH), 119.1 (@CH), 109.2
(@CH), 105.4 (quat-C), 70.6 (OCH2), 70.3 (OCH2), 68.6 (OCH2), 64.6
(OCH2), 49.4 (NCH3), 32.7 (CH). HRMS (ESI+) calcd for
C20H25NO7Na (M+Na)+: 414.1529, found 414.1513.
15. General procedure for the synthesis of indolyl cryptands 10, 11: To an
oven dried flask, bis-diazocarbonyl compound 5e, g (0.3 mmol) and
1,10-(1,2-phenylenbis(methylene))-bis(1H-indole) or 1,10-butane-1,4-
diylbis(1H-indole) (0.3 mmol) in dry benzene (100 mL) were charged
under an inert atmosphere. To the above reaction mixture, 2 mol % of
rhodium(II) acetate was added and the mixture refluxed for 6 h.
Progress of the reaction was monitored by TLC. The solvent was
removed under reduced pressure and the resulting residue purified
using 100–200 mesh silica gel column chromatography (hexane/
EtOAc) to afford the respective cryptands 10 or 11. Bis-indol-3-yl
cryptand 10: Brown thick oil; mmax (neat)/cmꢁ1 2930, 1730, 1465, 1144,
911, 731. 1H NMR (CDCl3, 200 MHz) d 7.58 (d, 2H, Arom-H), 7.36–
7.01 (m, 8H, Arom-H), 5.00 (s, 2H, CH), 4.22–4.09 (m, 12H, OCH2,
NCH2), 1.95–1.35 (m, 20H, CH2). 13C NMR (CDCl3, 50.3 MHz) d
168.3 (C@O), 135.5 (quat-C), 127.6 (@CH), 127.3 (quat-C), 126.7