Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2014; 25(07): 1001-1005
DOI: 10.1055/s-0033-1340864
DOI: 10.1055/s-0033-1340864
letter
3,3-Dichloro-1,2-diphenylcyclopropene (CPICl)-Mediated Synthesis of Nα-Protected Amino Acid Azides and α-Ureidopeptides
Further Information
Publication History
Received: 05 December 2013
Accepted after revision: 04 February 2014
Publication Date:
14 March 2014 (online)
![](https://www.thieme-connect.de/media/synlett/201407/lookinside/thumbnails/10.1055-s-0033-1340864-1.jpg)
Abstract
Rapid synthesis of acid azides via in situ generation of acid chlorides using CPICl as chlorinating agent from the corresponding Nα-protected amino acids is described. Also the conversion of acid azides into ureidopeptides through the Curtius rearrangement under ultrasonication is delineated. The mildness of the protocol renders the acid-sensitive substrates to afford the corresponding amino acid azides and ureidopeptides in good yields. Diphenylcyclopropenone has also been recovered from the reaction mixture and reused.
Keywords
Nα-protected amino acids - CPICl - acid chlorides - acid azides - Curtius rearrangement - ureidopeptidesSupporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References and Notes
- 1a Bräse S, Zimmermann V, Gil C, Knepper K. Angew. Chem. Int. Ed. 2005; 44: 5188
- 1b Scriven EF. V, Turnbull K. Chem. Rev. 1988; 88: 297
- 2a Lago JM, Arrieta A, Palomo C. Synth. Commun. 1983; 13: 289
- 2b Arrieta A, Aizpurua JM, Palomo C. Tetrahedron Lett. 1984; 25: 3365
- 2c Canone P, Akssira M, Dahouh A. Heterocycles 1993; 36: 1305
- 2d Froeyen P. Phosphorus, Sulfur Silicon Relat. Elem. 1994; 89: 57
- 2e Shao H, Colucci M, Tong S. Tetrahedron Lett. 1998; 39: 7235
- 2f Bandgar BP, Pandit SS. Tetrahedron Lett. 2002; 43: 3413
- 2g Gumaste VK, Bhawal BM, Deshmukh AR. A. S. Tetrahedron Lett. 2002; 43: 1345
- 2h Sridhar R, Perumal PT. Synth. Commun. 2003; 33: 607
- 2i Kangani CO, Day BW, Kelley DE. Tetrahedron Lett. 2007; 48: 5933
- 2j Kim JG, Jang DO. Synlett 2008; 2072
- 2k Vasantha B, Sureshbabu VV. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2010; 49: 812
- 2l Kitamura M, Tashiro N, Takamoto Y, Okauchi T. Chem Lett. 2010; 39: 732
- 2m Nowrouzi N, Jonaghani MZ. Chin. Chem. Lett. 2012; 23: 442
- 3 Tale RH, Patil KM. Tetrahedron Lett. 2002; 43: 9716
- 4 Lebel H, Leogane O. Org. Lett. 2005; 7: 4107
- 5 Akhlaghinia B, Rouhi-Saadabad H. Can. J. Chem. 2013; 91: 181
-
6 Padwa A, Brodney MA, Liu B, Satake K, Wu T. J. Org. Chem. 1999; 64: 3595
- 7 Kuramochi K, Osada Y, Kitahara T. Tetrahedron 2003; 59: 9447
- 8 Papeo G, Posteri H, Vianello P, Varasi M. Synthesis 2004; 2886
- 9 Katritzky AR, Widyan K, Kirichenko K. J. Org. Chem. 2007; 72: 5802
- 10 Suresh Babu VV, Ananda K, Vasanthakumar GR. J. Chem. Soc., Perkin Trans. 1 2000; 4328
- 11a Pfister JR, Wymann WE. Synthesis 1983; 38
- 11b Surya Prakash GK, Iyer PS, Arvanaghi M, Olah GA. J. Org. Chem. 1983; 48: 3358
- 12a Lee JG, Kwak KH. Tetrahedron Lett. 1992; 33: 3165
- 12b Chen DJ, Zhen ZC. Tetrahedron Lett. 2000; 41: 7361
- 12c Elmorsy SS. Tetrahedron Lett. 1995; 36: 1341
- 12d Marinescu L, Thinggaard J, Thomsen IB, Bols M. J. Org. Chem. 2003; 68: 9453
- 12e Arote ND, Akamanchi KG. Tetrahedron Lett. 2007; 48: 5661
- 12f Bose DS, Reddy AV. N. Tetrahedron Lett. 2003; 44: 3543
- 12g Sarkar SD, Studer A. Org. Lett. 2010; 12: 1992
- 13a Breslow R. J. Am. Chem. Soc. 1957; 79: 5318
- 13b Komatsu K, Kitagawa T. Chem. Rev. 2003; 103: 1371
- 14a Wass DF, Haddow MF, Hey TW, Orpen AG, Russell CA, Wingad RL, Green M. Chem. Commun. 2007; 2704
- 14b Green M, McMullin CL, Morton GJ. P, Orpen AG, Wass DF, Wingad RL. Organometallics 2009; 28 1476
- 14c Chotima R, Dale T, Green M, Hey TW, Mcmullin CL, Nunns A, Orpen AG, Shishkov IV, Wass DF, Wingad RL. Dalton Trans. 2011; 40: 5316
- 15a Kelly BD, Lambert TH. J. Am. Chem. Soc. 2009; 131: 13930
- 15b Hardee DJ, Kovalchuke L, Lambert TH. J. Am. Chem. Soc. 2010; 132: 5002
- 15c Vanos CM, Lambert TH. Angew. Chem. Int. Ed. 2011; 50: 12222
- 16a Kelly BD, Lambert TH. Org. Lett. 2011; 13: 740
- 16b Nacsa ED, Lambert TH. Org. Lett. 2013; 15: 38
- 17a Vanos CM, Lambert TH. Chem. Sci. 2010; 1 705
- 17b Srivastava VP, Patel Garima R, Yadav LD. S. Chem. Commun. 2010; 46: 5808
- 17c Tian BX, An N, Deng WP, Eriksson LA. J. Org. Chem. 2013; 78: 6782
- 18 Nogueira JM, Nguyen SH, Bennett CS. Org. Lett. 2011; 13: 2814
- 19a Breslow R, Posner J. Org. Synth. 1967; 47: 62
- 19b Fohlisch B, Burgle P. Liebigs Ann. Chem. 1967; 701: 67
- 19c Perkins WC, Wadsworth DH. Synthesis 1972; 205
- 20 General Procedure for the Synthesis of N α-Fmoc/Cbz-Amino Acid Azides 2 Oxalyl chloride (1.0 equiv) was added to a solution of diphenylcyclopropenone (1.1 equiv) in CH2Cl2 at r.t. After gas evolution had ceased, a solution of Nα-protected amino acid (1.0 equiv) and DIPEA (2.2 equiv) in CH2Cl2 was added at –15 °C followed by stirring for 5 min and then TMSN3 (1.5 equiv) was added. After stirring for an additional 5–10 min, the reaction mixture was diluted with CH2Cl2, washed with citric acid (10%), sat. NaHCO3 (10%), and sat. NaCl solutions. The organic phase was dried over anhydrous Na2SO4 and concentrated. The crude residue was purified by flash chromatography (20% EtOAc in hexane) to obtain pure acid azide. Diphenylcyclopropenone was recovered in approximately the same yield.
- 21 Suresh Babu VV, Patil BS, Venkataramanarao R. J. Org. Chem. 2006; 71: 7697
- 22a Guichard G, Semetey V, Didierjean C, Aubry A, Briand JP, Rodriguez M. J. Org. Chem. 1999; 64: 8702
- 22b Fischer L, Semetey V, Lozano JM, Schaffner AP, Briand JP, Didierjean C, Guichard G. Eur. J. Org. Chem. 2007; 2511
- 23 Suresh Babu VV, Lalithamba HS, Narendra N, Hemantha HP. Org. Biomol. Chem. 2010; 8: 835
- 24 General Procedure for the Synthesis of N α-Boc/Cbz/Fmoc-Ureidopeptides 5 Oxalyl chloride (1.0 equiv) was added to a solution of diphenylcyclopropenone (1.1 equiv) in CH2Cl2 at r.t. After gas evolution had ceased, a solution of Nα-protected amino acid (1.0 equiv) and DIPEA (2.2 equiv) in CH2Cl2 was added at –15 °C followed by stirring for 5 min, TMSN3 (1.5 equiv) was added to the reaction mixture. After stirring for an additional 5–10 min, toluene was added to the reaction mixture which was subjected to ultrasonication at 45 °C for about 20 min followed by addition of amino acid methyl ester, and the ultrasonication was continued until completion of the reaction. The solvent was removed in vacuo. The residue was washed with citric acid (10%) and NaHCO3 (10%) solutions and triturated 2–3 times with Et2O (5 mL) and filtered. The solid obtained was then recrystallized using DMSO–H2O (8:2). The diphenylcyclopropenone was also recovered from ether layer and reused.
- 25a Sureshbabu VV, Chennakrishnareddy G, Narendra N. Tetrahedron Lett. 2008; 49: 1408
- 25b Basavaprabhu Narendra N, Lamani RS, Sureshbabu VV. Tetrahedron Lett. 2010; 51: 3002
- 26 The possibility of the epimerization for the two epimeric ureidopeptides was analyzed through 1H NMR spectroscopy, which were prepared from Boc-(l)-Phe-OH and optically pure (R)-(+)- and (S)-(–)-1-phenylethylamine using the present method. The 1H NMR spectra of Boc-(l)-Phe-Ψ(NHCONH)-(R)-(+)-1-phenylethylamine (5k) and Boc-(l)-Phe-Ψ(NHCONH)-(S)-(–)-1-phenylethylamine (5l) contained the (R)- and (S)-1-phenylethylamine methyl group doublet at δ = 1.28, 1.30 and 1.25, 1.27 ppm, respectively. Whereas Boc-(l)-Phe-Ψ(NHCONH)-(R,S)-(±)-1-phenylethylamine (5k + 5l) contained two separate doublets at δ = 1.25, 1.27, 1.28, 1.30 ppm for (R,S)-(±)-1-phenylethylamine methyl groups (Figure 1). This clearly indicates that the present protocol is free of epimerization.
-
27
Selected Spectroscopic Data
Fmoc-Ile-N3 (2a)23 Yield 94%; mp 152 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 0.88–0.92 (m, 3 H), 1.02–1.37 (m, 5 H), 1.87–1.99 (m, 1 H), 4.45–4.49 (m, 2 H), 4.54 (d, J = 6.3 Hz, 2 H), 5.14 (s, 1 H), 7.29–7.80 (m, 8 H). 13C NMR (100 MHz, DMSO-d 6): δ = 11.62, 15.10, 25.71, 30.03, 47.57, 55.82, 67.09, 120.49, 125.76, 127.67, 128.29, 141.58, 144.27, 156.63, 180.03. HRMS: m/z calcd for C21H22N4NaO3: 401.1590; found: 401.1596 [M + Na]+. (Z)-Ala-Ψ[NH-CO-NH]-Gly-OMe (3h)23 Yield 91%; mp 141–143 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 1.40 (d, J = 7.7 Hz, 3 H), 3.57 (s, 3 H), 4.45 (d, J = 6.5 Hz, 2 H), 5.13 (s, 2 H), 5.01–5.06 (m, 1 H), 5.66 (br, 1 H), 6.50 (br, 2 H), 7.22–7.38 (m, 5 H). 13C NMR (100 MHz, DMSO-d 6): δ = 21.56, 41.23, 51.49, 59.78, 64.94, 127.43, 127.61, 128.57, 137.22, 155.07, 156.28, 171.75. HRMS: m/z calcd for C14H19N3NaO5: 332.1222; found: 332.1225 [M + Na]+. Boc-Ser(Bn)-Ψ[NH-CO-NH]-Gly-OMe (5j)24 Yield 87%; mp 133 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 1.34 (s, 9 H), 3.44–3.48 (m, 2 H), 3.62 (s, 3 H), 3.84 (d, J = 6.9 Hz, 2 H), 4.49 (s, 2 H), 4.94–4.97 (m, 1 H), 5.78 (br, 1 H), 6.48 (br, 1 H), 6.54 (br, 1 H), 7.26–7.38 (m, 5 H). 13C NMR (100 MHz, DMSO-d 6): δ = 28.63, 45.51, 53.56, 71.57, 76.61, 77.45, 78.77, 126.61, 127.36, 128.53, 138.14, 156.38, 157.25, 171.35. HRMS: m/z calcd for C18H27N3NaO6: 404.1798; found: 404.1797 [M + Na]+.