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Synlett 2012; 23(18): 2687-2691
DOI: 10.1055/s-0032-1317382
DOI: 10.1055/s-0032-1317382
letter
One-Pot Enantioselective Synthesis of Tryptophan Derivatives via Phase-Transfer Catalytic Alkylation of Glycine Using a Cinchona-Derived Catalyst
Further Information
Publication History
Received: 12 July 2012
Accepted after revision: 18 September 2012
Publication Date:
18 October 2012 (online)
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Abstract
Tryptophans are building blocks for many natural products. This paper describes the enantiospecific synthesis of ring-A substituted tryptophan derivatives from commercially available gramines using chiral phase-transfer conditions. This one-pot reaction avoids protecting/deprotecting the indolylic nitrogen of gramine by choosing a chemoselective quaternization reagent, 4-(trifluoro-methoxy)benzyl bromide, to produce an electrophilic salt intermediate, which is subsequently alkylated in good yield with high enantiomeric excess.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
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References and Notes
- 1a Dalpozzo R, Bartoli G. Curr. Org. Chem. 2005; 9: 163
- 1b Mori M. J. Organomet. Chem. 2004; 689: 4210
- 1c Phillips RS. Tetrahedron: Asymmetry 2004; 15: 2787
- 1d Gribble GW. Pure Appl. Chem. 2003; 75: 1417
- 1e Meister A. Biochemistry of the Amino Acids . Academic Press; New York: 1965: 202
- 2a Rahman A, Basha A. Indole Alkaloids . Harwood Academic Publishers; Amsterdam: 1998: 141
- 2b Gupta RR, Kumar M, Gupta V. Heterocyclic Chemistry II: Five-Membered Heterocycles . Springer Publishing; New York: 1999: 193
- 2c Physicians’ Desk Reference . 51st ed. Medical Economics, Co; Oradell (NJ, USA): 1997: 2395
- 2d Physicians’ Desk Reference . 51st ed. Medical Economics, Co; Oradell (NJ, USA): 1997: 1723
- 2e For a review on medicinal chemistry of vinblastine, see: Borman LS, Kuehne ME, Pearce HL. In The Alkaloids: Antitumor Bisindole Alkaloids from Catharanthus roseus (L.) . Vol. 37; Brossi A. Academic Press Inc; San Diego: 1990: 133
- 3a Kieffer M, Repka L, Reisman S. J. Am. Chem. Soc. 2012; 134: 5131
- 3b Zheng B, Ding C, Hou X, Dai L. Org. Lett. 2010; 12: 1688
- 3c Jain HD, Zhang C, Zhou S, Zhou H, Ma J, Liu X, Liao X, Deveau AM, Dieckhaus M, Johnson MA, Smith KS, Macdonald TL, Kakeya H, Osada H, Cook JM. Bioorg. Med. Chem. 2008; 16: 4626
- 3d Dacko CA, Akhmedov NG, Soderberg BC. G. Tetrahedron: Asymmetry 2008; 19: 2775
- 3e Ma J, Yin W, Zhou H, Cook JM. Org. Lett. 2007; 9: 3491
- 3f Li X, Yin W, Sarma PV. V. S, Zhou H, Ma J, Cook JM. Tetrahedron Lett. 2004; 45: 8569
- 3g Castle SL, Srikanth GS. C. Org. Lett. 2003; 5: 3611
- 3h Ma C, Liu X, Li X, Flippen-Anderson J, Yu S, Cook JM. J. Org. Chem. 2001; 66: 4525
- 3i Wang H, Usui T, Osada H, Ganesan A. J. Med. Chem. 2000; 43: 1577
- 3j Drury W, Ferraris D, Cox C, Young B, Lectka T. J. Am. Chem. Soc. 1998; 120: 11007
- 3k Gan T, Liu R, Yu P, Zhao S, Cook JM. J. Org. Chem. 1997; 62: 9298
- 3l Yamada S, Yamamoto M, Hongo C, Chibata I. J. Agric. Food Chem. 1975; 23: 653
- 4a Maruoka K, Ooi T. Angew. Chem. Int. Ed. 2007; 46: 4222
- 4b Maruoka K. Pure Appl. Chem. 2005; 77: 1285
- 4c Lygo B, Andrews B. Acc. Chem. Res. 2004; 37: 518
- 4d Maruoka K, Ooi T. Chem. Rev. 2003; 103: 3013
- 4e O’Donnell MJ. Aldrichimica Acta 2001; 34: 3
- 5a Christiansen M, Butler A, Hill A, Andrus M. Synlett 2009; 653
- 5b Barraja P, Diana P, Carbone A, Cirrincione G. Tetrahedron 2008; 64: 11625
- 5c Lee Y.-J, Lee J, Kim M.-J, Kim T.-S, Park H.-g, Jew S.-s. Org. Lett. 2005; 7: 1557
- 5d O’Donnell MJ. Acc. Chem. Res. 2004; 37: 506
- 5e Ooi T, Takeuchi M, Kameda M, Maruoka K. J. Am. Chem. Soc. 2000; 122: 5228
- 5f Pirrung MG, Krishnamurthy N. J. Org. Chem. 1993; 58: 957
- 5g O’Donnell MJ, Eckrich TM. Tetrahedron Lett. 1978; 47: 4625
- 6 Joule JA, Mills K. Heterocyclic Chemistry . 5th ed. John Wiley & Sons; Chichester: 2010: 324
- 7 Dobish MC, Johnston JN. Org. Lett. 2010; 12: 5744
- 8 Synthesis of tert-Butyl 2-(Diphenylmethyleneamino)-3-(1H-indol-3-yl)propanoate (Scheme 6; Compound 5a); Typical Procedure: To a solution of gramine (0.300 g, 1.7 mmol, 1 equiv) in CH2Cl2 (10 mL) was added 4-(trifluoromethoxy)benzyl bromide (0.430 g, 1.7 mmol, 1 equiv) and the mixture was stirred for 30 min. N-(Diphenylmethylene)glycine tert-butyl ester (0.502 g, 1.7 mmol, 1 equiv) and O-allyl-N-(9-anthracenylmethyl)cinchoninium bromide (0.209 g, 0.3 mmol, 0.2 equiv) were added to the solution. The reaction mixture was then cooled to –30 °C. While stirring, solid KOH (2.0 g, 36 mmol, 20 equiv) and deionized H2O (0.2 mL, 11.1 mmol, 6 equiv) were added to the reaction mixture, which was stirred for an additional 12 h at –30 °C. The reaction mixture was concentrated by rotary evaporation and the products were isolated by column chromatography (silica gel; EtOAc–pentane, 10%) providing 5a (0.580 g, 80% yield) as a yellow oil. The identity of 5a was confirmed by comparing its spectra to those of 1H NMR spectra from authentic samples.9 tert-Butyl 2-(Diphenylmethyleneamino)-3-(5-methoxy-1H-indol-3-yl)propanoate (Scheme 6 ; Compound 8): 1H NMR (300 MHz, CDCl3): δ = 8.19 (s, 1 H), 7.59 (d, J = 7.9 Hz, 2 H), 7.27–7.43 (m, 4 H), 7.15–7.20 (m, 3 H), 6.93 (s, 1 H), 6.78–6.83 (m, 2 H), 6.61 (d, J = 7.5 Hz, 2 H), 4.33 (dd, J = 8.7, 4.5 Hz, 1 H), 3.69 (s, 3 H), 3.44 (dd, J = 14.1, 4.5 Hz, 1 H), 3.30 (dd, J = 14.1, 8.7 Hz, 1 H), 1.47 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 171.4, 170.1, 153.6, 139.6, 136.1, 131.1, 130.0, 128.7, 128.3, 128.0, 127.9, 127.6, 124.0, 112.0, 111.8, 111.6, 100.5, 81.0, 66.6, 55.7, 45.2, 29.3, 28.0. HRMS: m/z [M + H]+ calcd. for C29H30N2O3: 455.2335; found: 455.2353. tert-Butyl 2-(Diphenylmethyleneamino)-3-(6-methoxy-1H-indol-3-yl)propanoate (Scheme 6; Compound 9): 1H NMR (300 MHz, CDCl3): δ = 8.39 (s, 1 H), 7.63–7.71 (d, J = 7.9 Hz, 2 H), 7.28–7.41 (m, 4 H), 7.18–7.25 (m, 3 H), 6.84 (d, J = 2.4 Hz, 2 H), 6.67–6.80 (m, 3 H), 4.36 (dd, J = 8.4, 4.8 Hz, 1 H), 3.82 (s 3 H), 3.46 (dd, J = 14.1, 4.8 Hz, 1 H), 3.27 (dd, J = 14.1, 8.4 Hz, 1 H), 1.48 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 171.5, 170.2, 156.1, 139.6, 136.7, 136.2, 130.1, 128.7, 128.1, 128.0, 127.9, 127.6, 122.0, 119.4, 111.7, 109.0, 94.4, 80.9, 66.8, 55.6, 45.2, 29.4, 28.0. HRMS: m/z [M + H]+ calcd. for C29H30N2O3: 455.2335; found: 455.2349. tert-Butyl 3-(5-Bromo-1H-indol-3-yl)-2-(diphenyl-methyleneamino)propanoate (Scheme 6; Compound 10): 1H NMR (300 MHz, CDCl3): δ = 8.09 (s, 1 H), 7.80–7.90 (d, J = 7.9 Hz, 2 H), 7.60–7.70 (m, 3 H), 7.18–7.41 (m, 9 H), 7.00 (s, 1 H), 6.65 (d, J = 3.32 Hz, 2 H), 4.24 (dd, J = 8.4, 4.8 Hz, 1 H), 3.36 (dd, J = 14.1, 4.8 Hz, 1 H), 3.21 (dd, J = 14.1, 8.4 Hz, 1 H), 1.45 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 171.0, 170.2, 135.9, 134.5, 130.0, 129.9, 128.6, 128.3, 128.2, 128.0, 127.9, 127.4, 124.4, 124.3, 121.6, 112.4, 112.2, 112.0, 81.0, 66.4, 28.9, 28.0. HRMS: m/z [M + H]+ calcd. for C28H27BrN2O2: 503.1334; found: 503.1297.
- 9 Tarzia G, Balsamini C, Spadoni G, Duranti E. Synthesis 1988; 514
For reviews in chiral PTC, see: