488
R. Xiong, K. E. Borbas
Letter
Synlett
(4) (a) Lindsey, J. S. Acc. Chem. Res. 2010, 43, 300.
(b) Shanmugathasan, S.; Edwards, C.; Boyle, R. W. Tetrahedron
2000, 56, 1025. (c) Plunkett, S.; Senge, M. O. ECS Trans. 2011, 35,
147.
(5) Pereira, N. A. M.; Pinho e Melo, T. M. V. D. Org. Prep. Proced. Int.
2014, 46, 183.
(6) Yao, Z.; Bhaumik, J.; Dhanalekshmi, S.; Ptaszek, M.; Rodriguez, P.
A.; Lindsey, J. S. Tetrahedron 2007, 63, 10657.
(7) Littler, B. J.; Miller, M. A.; Hung, C.-H.; Wagner, R. W.; O’Shea, D.
F.; Boyle, P. D.; Lindsey, J. S. J. Org. Chem. 1999, 64, 1391.
(8) Laha, J. K.; Dhanalekshmi, S.; Taniguchi, M.; Ambroise, A.;
Lindsey, J. S. Org. Process Res. Dev. 2003, 7, 799.
(9) (a) Herz, W.; Toggweiler, U. J. Org. Chem. 1964, 29, 213. (b) Hinz,
W.; Jones, R. A.; Anderson, T. Synthesis 1986, 620. (c) Rawal, V.
H.; Jones, R. J.; Cava, M. P. J. Org. Chem. 1987, 52, 19. (d) Kumar,
S.; Mani, G.; Mondal, S.; Chattaraj, P. K. Inorg. Chem. 2012, 51,
12527. (e) Mani, G.; Guchhait, T.; Kumar, R.; Kumar, S. Org. Lett.
2010, 12, 3910.
and the solvent was evaporated. The crude product was used
without further purification in the next step.
Dipyrromethane Synthesis
The Mannich product was placed in a microwave vial. Pyrrole
was added to afford a 0.2–0.3 M solution. The vial was capped.
The vial was placed in a microwave reactor and was irradiated
at 150 °C for 30 min. The reaction mixture was cooled to r.t., and
the pyrrole was evaporated. The dark brown oily residue was
purified by column chromatography (silica, PE–EtOAc) to afford
the products.
Compound 2e: yellow oil (62%); IR (thin film): ν = 3003, 2945,
2866, 2709, 1568, 1481, 1463, 1417, 1406, 1298, 1262, 1225,
1172, 1133, 1051, 1016 cm–1 1H NMR (400 MHz, CDCl3): δ =
.
1.08 (d, J = 7.4 Hz, 18 H), 1.43 (sept, J = 7.4 Hz, 3 H), 2.25 (s, 6 H),
3.42 (s, 2 H), 6.23–6.27 (m, 1 H), 6.64–6.69 (m, 1 H), 6.70–6.74
(m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 11.6, 17.8, 44.6, 56.2,
111.7, 121.4, 123.6, 124.3. ESI-HRMS: m/z calcd for C16H32N2Si
[M + H]+: 281.2363; found: 281.2406.
(10) (a) Fan, D.; Taniguchi, M.; Yao, Z.; Dhanalekshmi, S.; Lindsey, J. S.
Tetrahedron 2005, 61, 10291. (b) Schmidt, I.; Jiao, J.;
Thamyongkit, P.; Sharada, D. S.; Bocian, D. F.; Lindsey, J. S. J. Org.
Chem. 2006, 71, 3033. (c) Borbas, K. E.; Kee, H. L.; Holten, D.;
Lindsey, J. S. Org. Biomol. Chem. 2008, 6, 187. (d) Muresan, A. Z.;
Lindsey, J. S. Tetrahedron 2008, 64, 11440. (e) Lahaye, D.;
Muthukumaran, K.; Hung, C.-H.; Gryko, D.; Reboucas, J. S.;
Spasojevic, I.; Batinic-Haberle, I.; Lindsey, J. S. Bioorg. Med.
Chem. 2007, 15, 7066.
(11) Dogutan, D. K.; Ptaszek, M.; Lindsey, J. S. J. Org. Chem. 2007, 72,
5008.
(12) Ptaszek, M.; McDowell, B. E.; Taniguchi, M.; Kim, H.-J.; Lindsey, J.
S. Tetrahedron 2007, 63, 3826.
Compound 3e: colorless oil (54%); IR (thin film): ν = 3676, 3341,
2959, 2867, 1563, 1534, 1464, 1407, 1394, 1383, 1272, 1258,
1236, 1210, 1116, 1067, 1016 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 1.19 (d, J = 7.6 Hz, 18 H), 1.50 (sept, J = 7.6 Hz, 3 H), 3.95 (s, 2
H), 5.97 (s, 1 H), 6.18–6.24 (m, 1 H), 6.25–6.29 (m, 1 H), 6.65–
6.73 (m, 2 H), 6.79–6.87 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ
= 11.8, 17.9, 25.5, 105.0, 108.3, 111.3, 116.0, 122.2, 122.7, 124.7,
132.2. ESI-HRMS: m/z calcd for C18H30N2Si [M + H]+: 303.2251;
found: 303.2247.
Compound 2f: colorless oil (quant.); 1H NMR (400 MHz, CDCl3):
δ = 1.17 (t, J = 7.2 Hz, 3 H), 2.02 (s, 1.5 H), 2.17 (s, 4 H), 2.31 (s,
1.5 H), 3.33 (d, J = 11.9 Hz, 2 H), 4.12 (q, J = 7.6 Hz 1 H), 4.67 (s,
0.5 H), 7.01 (dd, J = 15.3, 8.2 Hz, 2 H), 7.38 (d, J = 10.6 Hz, 1 H),
7.66 (dd, J = 9.3, 7.7 Hz, 2 H). 10.4 (br, 1 H). 13C NMR (100 MHz,
CDCl3): δ = 14.2, 14.4, 42.7, 44.8, 52.5, 54.0, 59.4, 70.4, 92.1,
114.2, 123.2, 124.4, 127.7, 128.1, 132.6, 132.8, 134.3, 136.4,
136.6, 164.6. ESI-HRMS: m/z calcd for C16H19N2O2I [M + MeOH +
Na]+: 456.0888; found: 456.0894.
(13) Toganoh, M.; Furuta, H. Chem. Commun. 2012, 48, 937.
(14) Jolicoeur, B.; Chapman, E. E.; Thompson, A.; Lubell, W. D. Tetra-
hedron 2006, 62, 11531.
(15) (a) Kim, H.-J.; Lindsey, J. S. J. Org. Chem. 2005, 70, 5475.
(b) Borbas, K. E.; Ruzie, C.; Lindsey, J. S. Org. Lett. 2008, 10, 1931.
(16) General Procedure for the Mannich Reaction
A sample of the heterocycle was dissolved in CH2Cl2 or MeCN
(ca. 0.15–0.2 M). Eschenmoser’s salt (2 equiv) was added in a
single portion. The reaction mixture was stirred at r.t. until TLC
analysis indicated the complete consumption of the starting
material (20 min to 26 h). The reaction mixture was diluted
with CH2Cl2 or EtOAc (for MeCN as solvent) and sat. aq NaHCO3.
The phases were separated, and the aqueous layer was
extracted once. The organic layer was dried (Na2SO4), filtered,
Compound 3f: pale solid (52%); 1H NMR (400 MHz, CDCl3/
CD3OD): δ = 1.14 (dt, J = 7.1, 1.2 Hz, 3 H), 3.76 (s, 1 H), 4.08 (q, J
= 7. 2 Hz 2 H), 5.72–5.81 (m, 1 H), 5.94–6.05 (m, 1 H), 6.58–6.63
(m, 1 H), 7.04 (d, J = 8. 4 Hz, 2 H), 7.33–7.39 (m, 1 H), 7.61 (d, J =
8. 4 Hz, 2 H). 13C NMR (100 MHz, CDCl3/CD3OD): δ = 13.7, 24.0,
59.4, 91.3, 105.6, 107.5, 113.3, 116.8, 121.1, 124.1, 128.8, 129.0,
132.4, 134.8, 136.4, 165.8. ESI-HRMS: m/z calcd for C16H19N2O2I
[M + MeOH + Na]+: 456.0888; found: 456.0894.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 484–488