RSS-Feed abonnieren
DOI: 10.1055/s-2008-1032091
Highly Efficient Domino Reaction for the Synthesis of the Erythrina and B-Homoerythrina Alkaloid Skeleton
Publikationsverlauf
Publikationsdatum:
12. Februar 2008 (online)
![](https://www.thieme-connect.de/media/synlett/200804/lookinside/thumbnails/10.1055-s-2008-1032091-1.jpg)
Abstract
A Lewis acid catalyzed domino-amidation-spirocyclization reaction is described which provides the spirocyclic core of the erythrina and B-homoerythrina alkaloids, forming three bonds in one process.
Key words
domino reactions - erythrina alkaloids - spiro compounds - Lewis acids - indolizidine - lactams
-
1a
Tietze LF.Brasche G.Gericke KM. Domino Reactions in Organic Synthesis Wiley-VCH; Weinheim: 2006. -
1b
Tietze LF.Haunert F. In Stimulating Concepts in ChemistryShibasaki M.Stoddart JF.Vögtle F. Wiley-VCH; Weinheim: 2000. p.39 -
1c
Tietze LF.Modi A. Med. Res. Rev. 2000, 20: 304 -
1d
Tietze LF. Chem. Rev. 1996, 115 -
1e
Tietze LF.Beifuss U. Angew. Chem., Int Ed. Engl. 1993, 32: 131 - 2
Krukoff BA.Barneby RC. Mem. New York Bot. Gard. 1970, 20: 1 -
3a
Chawla AS.Kapor VK. In Handbook of Plant and Fungal ToxicantsD’Mello JF. CRC Press; New York: 1997. p.37 -
3b
Bhakuni DS. J. Indian Chem. Soc. 2002, 203 -
3c
Lehman AJ. J. Pharmacol. 1937, 69 -
3d
Williams M.Robinson JL. J. Neurosci. 1984, 2906 -
3e
Decker MW.Anderson DJ.Brioni JD.Donnelly-Roberts DL.Kang CH.O’Neil AB.Piattoni-Kaplan M.Swanson S.Sullivan JP. Eur. J. Pharmacol. 1995, 79 -
4a
Boekelheide V. In The Alkaloids Vol. 7:Manske RHF. Academic Press; New York: 1960. p.201 -
4b
Hill RK. In The Alkaloids Vol. 9:Manske RHF. Academic Press; New York: 1967. p.483 -
4c
Dyke SF.Quessy SN. In The Alkaloids Vol. 18:Rodrigo RGA. Academic Press; New York: 1981. p.1 -
4d
Jackson AH. In Chemistry and Biology of Isoquinoline AlkaloidsPhillipson JD.Margaret MF.Zenk MH. Springer; Berlin: 1985. p.62 -
4e
Chawla AS.Jackson AH. Nat. Prod. Rep. 1984, 1: 371 -
5a
Stanislawski PC.Willis AC.Banwell MG. Org. Lett. 2006, 8: 2143 -
5b
Padwa A.Wang Q. J. Org. Chem. 2006, 71: 7391 -
5c
Ganguly AK.Wang CH.Biswas D.Misiaszek J.Micula A. Tetrahedron Lett. 2006, 47: 5539 -
5d
Gao S.Tu YQ.Hu X.Wang S.Hua R.Jiang Y.Zhao Y.Fan X.Zhang S. Org. Lett. 2006, 8: 2373 -
5e
Fukumoto H.Takahashi K.Ishihara J.Hatakeyama S. Angew. Chem. Int. Ed. 2006, 45: 2731 - 7
El Bialy SAA.Braun H.Tietze LF. Angew. Chem. Int. Ed. 2004, 43: 5391
References and Notes
General Procedure
To a stirred solution of amine 2 (1.00 equiv) in MeCN (0.5 mL/mmol) was added dropwise at 0 °C AlMe3 (2.00 M in toluene, 2.00 equiv), then In(OTf)3 (4-25 mol%) and the ester 3 (1.00 equiv), and stirring was continued for 3-17 h at r.t. or the mixture was heated to 100-180 °C under microwave irradiation. The reaction mixture was cooled to 0 °C, TfOH (3.5 equiv) was added dropwise and stirring was continued for 5 h at r.t. Subsequently, the mixture was quenched by addition of sat. aq NaHCO3 at 0 °C with stirring for 20 min. The mixture was extracted with EtOAc, the combined organic layers were washed with brine, dried over Na2SO4, and the solvent was removed under reduced pressure. The crude product was subjected to column chromatography to yield 38-99% of the spirocycle 4.
Compound 4a: 1H NMR (300 MHz, DMSO): d = 1.35-1.60 (m, 5 H, 3-H2, 2-H2, 1-Ha), 1.75-1.82 (m, 2 H, 4-H2), 1.95-1.99 (m, 1 H, 1-Hb), 2.12 (mc, 2 H, 7-H2), 2.54-2.60 (m, 1 H, 6-H), 2.63 (ddd, J = 3.0, 6.0, 16.5 Hz, 1 H, 11-Ha), 2.80 (ddd, J = 7.4, 10.0, 16.5 Hz, 1 H, 11-Hb), 3.15 (ddd, J = 6.0, 10.0, 13.2 Hz, 1 H, 10-Ha), 3.71 (s, 3 H, OCH3), 3.76 (s, 3 H, OCH3), 3.86 (ddd, J = 3.0, 7.4, 13.2 Hz, 1 H, 10-Hb), 6.67 (s, 1 H, 17-H), 6.91 (s, 1 H, 14-H). 13C NMR (300 MHz, DMSO): d = 20.06 (C-2), 20.57 (C-3), 26.14 (C-11), 27.17 (C-1), 34.26 (C-10), 35.01 (C-4), 36.29 (C-7), 36.67 (C-6), 55.42 (OCH3), 55.74 (OCH3), 61.75 (C-5), 108.7 (C-14), 112.5 (C-17), 125.5 (C-12), 134.7 (C-13), 147.0 (C-16), 147.5 (C-15), 173.6 (C-8).
Compound 4b: 1H NMR (300 MHz, DMSO): d = 1.18-1.42 (m, 2 H, 11-Ha, 13*-Ha), 1.42-1.69 (m, 5 H, 2-H2, 12*-H2, 13*-Hb), 1.69-1.82 (m, 2 H, 1-H2), 2.05 (dd, J = 18.5, 6.2 Hz, 1 H, 14-Ha), 2.18-2.26 (m, 1 H, 11-Hb), 2.33-2.47 (m, 1 H, 14-Hb), 2.52 (d, J = 5.9 Hz, 1 H, 6-Ha), 2.63 (mc, 1 H, 14a-H), 2.84-2.99 (m, 1 H, 6-Hb), 3.19 (td, J = 12.3, 5.9 Hz, 1 H, 5-Ha), 3.70 (s, 3 H, OCH3), 3.73 (s, 3 H, OCH3), 4.53 (dd, J = 13.2, 7.5 Hz, 1 H, 5-Hb), 6.62 (s, 1 H, 7-H), 6.82 (s, 1 H, 10-H). 13C NMR (300 MHz, DMSO): d = 21.42 (C-13*), 22.15 (C-12*), 25.07 (C-1), 25.60 (C-2), 26.06 (C-6), 28.14 (C-14), 34.48 (C-5), 34.77 (C-14a), 39.58 (C-11), 55.32 (OCH3), 55.89 (OCH3), 60.99 (C-10b), 107.2 (C-10), 112.9 (C-7), 126.5 (C-6a), 135.8 (C-10a), 146.9 (C-9), 147.4 (C-8), 171.0 (C-3).
Compound 4c: 1H NMR (300 MHz, DMSO): d = 1.28-1.48 (m, 3 H, 3-H2, 1-Ha), 1.49-1.58 (m, 2 H, 2-H2), 1.71-1.75 (m, 1 H, 4-Ha), 1.78-1.83 (m, 1 H, 4-Hb), 1.91-1.99, (m, 1 H, 1-Hb), 2.09-2.14 (m, 2 H, 7-H2), 2.49-2.54 (m, 1 H, 6-H), 2.59-2.67 (m, 1 H, 11-Ha), 2.73-2.87 (m, 1 H, 11-Hb), 3.11-3.21 (m, 1 H, 10-Ha), 3.78-3.85 (m, 1 H, 10-Hb), 5.94 (s, 2 H, 18-H2), 6.65 (s, 1 H, 17-H), 6.97 (s, 1 H, 14-H). 13C NMR (300 MHz, DMSO): d = 19.90 (C-2), 20.49 (C-3), 26.58 (C-11), 27.02 (C-1), 34.25 (C-10), 35.01 (C-4), 36.22 (C-7), 36.71 (C-6), 62.13 (C-5), 100.7 (C-18), 104.9 (C-14), 108.7 (C-17), 126.8 (C-12), 135.9 (C-13), 145.6 (C-16), 145.7 (C-15), 173.6 (C-8).
Compound 4d: 1H NMR (300 MHz, DMSO): d = 1.20-1.35 (m, 2 H, 11-Ha, 13*-Ha), 1.35-1.52 (m, 2 H, 1-H2), 1.50-1.80 (m, 5 H, 2-H2, 12*-H2, 13*-Hb), 2.04 (dd, J = 18.6, 6.6 Hz, 1 H, 14-Ha), 2.18-2.25 (m, 1 H, 11-Hb), 2.32-2.44 (m, 1 H, 14-Hb), 2.55-2.70 (m, 2 H, 6-Ha, 14a-H), 2.80-2.92 (m, 1 H, 6-Hb), 3.14 (td, J = 11.9, 5.8 Hz, 1 H, 5-Ha), 4.52 (dd, J = 13.7, 7.4 Hz, 1 H, 5-Hb), 5.96 (s, 2 H, OCH2O), 6.61 (s, 1 H, 7-H), 6.92 (s, 1-H, 10-H).13C NMR (300 MHz, DMSO): d = 21.36 (C-13*), 22.07 (C-12*), 25.05 (C-1), 25.56 (C-2), 26.53 (C-6), 28.10 (C-14), 34.22 (C-5), 34.83 (C-14a), 39.62 (C-11), 61.12 (C-10b), 100.5 (OCH2O), 103.3 (C-10), 109.1 (C-7), 127.6 (C-6a), 137.0 (C-10a), 145.4 (C-9), 145.5 (C-8), 170.8 (C-3).
Compound 4e: 1H NMR (300 MHz, DMSO): d = 1.48-1.64 (m, 6 H, 11-Ha, 10-H2, 9-H2, 8-Ha), 1.82-1.87 (m, 1 H, 11-Hb), 1.94-1.99 (m, 1 H, 8-Hb), 2.10-2.19 (m, 2 H, 4-Ha, 8a-H), 2.39-2.48 (m, 1 H, 4-Hb), 2.48-2.74 (m, 2 H, 12-H2), 2.96 (td, J = 12.3, 6.7 Hz, 1 H, 5-Ha), 4.00-4.11 (qd, 1 H, J = 6.5, 1.3 Hz, 5-Hb), 6.85 (d, J = 5.4 Hz, 1 H, 3-H), 7.35 (d, J = 5.4 Hz, 1 H, 2-H). 13C NMR (300 MHz, DMSO): d = 19.57 (C-10), 21.00 (C-9), 24.46 (C-11), 25.10 (C-12), 33.16 (C-5), 34.43 (C-8), 34.54 (C-4), 40.33 (C-8a), 61.03 (C-12a), 122.9 (C-2), 126.9 (C-3), 132.4 (C-12b), 139.2 (C-3a), 171.0 (C-7).
Compound 4f: 1H NMR (300 MHz, DMSO-d
6): d = 1.35-1.61 (m, 4 H, 12-Ha, 13-H2, 12-Hb), 1.61-1.80 (m, 4 H, 10-H2, 9-Ha, 11-Ha), 1.84-1.94 (m, 2 H, 11-Hb), 2.03-2.09 (m, 1 H, 9a-H), 2.11-2.25 (m, 2 H, 8-Ha, 9-Hb), 2.37-2.49 (m, 1 H, 8-Hb), 2.53 (ddd, J = 1.0, 5.3, 16.5 Hz, 1 H, 4-Ha), 2.70 (ddd, J = 6.8, 11.7, 16.5 Hz, 1 H, 4-Hb), 3.16 (ddd, J = 5.3, 11.7, 13.3 Hz, 1 H, 5-Ha), 4.58 (ddd, J = 1.0, 6.8, 13.3 Hz, 1 H, 5-Hb), 6.80 (d, J = 5.0 Hz, 1 H, 3-H), 7.34 (d, J = 5.0 Hz, 1 H, 2-H). 13C NMR (75 MHz, DMSO-d
6): d = 21.69 (C-12), 22.77 (C-10), 23.10 (C-13), 24.30 (C-4), 26.82 (C-11), 29.68 (C-8), 34.88 (C-5), 38.20 (C-9), 39.34 (C-9a), 61.27 (C-13a), 122.8 (C-2), 127.3 (C-3), 134.3 (C-3a), 142.1 (C-13b), 170.2 (C-7).
Compound 4g: 1H NMR (300 MHz, DMSO-d
6): d = 1.46-1.68 (m, 6 H, 5-H2, 6-H2, 7-Ha, 4-Ha), 1.85-2.99 (m, 2 H, 7-Hb, 4-Hb), 2.14 (dd, J = 6.9, 14.0 Hz, 8-Ha), 2.21-2.29 (m, 1 H, 7a-H), 2.35 (ddd, J = 0.8, 8.9, 14.0 Hz, 1 H, 8-Hb), 2.70-2.86 (m, 2 H, 12-H2), 3.01-3.11 (m, 1 H, 11-Ha), 4.09-4.16 (m, 1 H, 11-Hb), 7.18 (d, J = 5.3 Hz, 1 H, 3-H), 7.35 (d, J = 5.3 Hz, 1 H, 2-H). 13C NMR (75 MHz, DMSO-d
6): d = 19.95 (C-5), 20.23 (C-6), 23.88 (C-12), 24.97 (C-7), 33.45 (C-11), 34.12 (C-4), 35.08 (C-8), 37.68 (C-7a), 61.10 (C-3b), 123.4 (C-2), 124.3 (C-3), 132.3 (C-12a), 140.8 (C-3a), 171.9 (C-9).
Compound 4h: 1H NMR (300 MHz, DMSO-d
6): d = 1.21-1.38 (m, 1 H, 4-Ha), 1.38-1.55 (m, 4 H, 4-Hb, 8-H2, 6-Ha), 1.55-1.68 (m, 2 H, 5-H2), 1.68-1.78 (m, 2 H, 7-H2), 2.09 (mc, 1 H, 9-Ha), 2.17-2.24 (m, 1 H, 6-Hb), 2.37-2.47 (m, 2 H, 7a-H, 9-Hb), 2.63 (dd, J = 5.3, 16.2 Hz, 1 H, 13-Ha), 2.90 (ddd, J = 6.9, 11.7, 16.2 Hz, 1 H, 13-Hb), 3.23 (ddd, J = 5.3, 11.7, 13.2 Hz, 1 H, 12-Ha), 4.58 (dd, J = 6.9, 13.2 Hz, 1 H, 12-Hb), 7.00 (d, J = 5.4 Hz, 1 H, 3-H), 7.27 (d, J = 5.4 Hz, 1 H, 2-H). 13C NMR (75 MHz, DMSO-d
6): d = 21.35 (C-4), 22.78 (C-8), 23.06 (C-13), 24.69 (C-7), 25.76 (C-5), 28.67 (C-9), 35.06 (C-12), 36.46 (C-7a), 38.31 (C-6), 61.42 (C-3b), 122.7 (C-3), 123.2 (C-2), 134.1 (C-13a), 143.21 (C-3a), 171.3 (C-10).