Copper-Assisted Arylation of 1-Thiosugars: Efficient Route to Triazene Substituted Arylthioglycosides

Abstract

Efficient copper mediated arylation of sugar thiols by o-haloaryl triazenes under mild conditions is described. The developed method allows the preparation of symmetrical and unsymmetrical 1,3-bis(glycopyranosylthio)benzene derivatives.

arylations - copper - sugar thiols - thioglycosides - tri­azenes

References

1a Horton D. Wander JD. In The Carbohydrates. Chemistry and Biochemistry   Vol. IB:  Pigman W. Horton D. Academic Press; New York: 1980.  p.799-842  

1b Driguez H. Top. Curr. Chem.  1997,  187:  85 

2 Choi JH. Choe YS. Lee KH. Choi Y. Kim SE. Kim BT. Carbohydr. Res.  2003,  338:  29 

3a Seevers RH. Counsell RE. Chem. Rev.  1982,  82:  575 

3b Wilbur DS. Bioconjugate Chem.  1992,  3:  433 

4 Electrophilic iodonium species are utilized for activation of thioglycosides in glycosylations and may cause their anomerization, see: Boons G.-J. Stauch T. Synlett  1996,  906 

5 Kimball DB. Haley MM. Angew. Chem. Int. Ed.  2002,  41:  3338 

6a Foster NI. Heindel ND. Burns HD. Muhr W. Synthesis  1980,  572 

6b Satyamurthy N. Barrio JR. J. Org. Chem.  1983,  48:  4394 

6c Satyamurthy N. Barrio JR. Schmidt DG. Kammerer C. Bida GT. Phelps ME. J. Org. Chem.  1990,  55:  4560 

6d Barbero M. Degani I. Diulgheroff N. Dughera S. Fochi R. Synthesis  2001,  2180 ; and references therein

7a Čern M. Vrkoč J. Staněk J. Collect. Czech. Chem. Commun.  1959,  24:  64 

7b Frgala J. Čern M. Staněk J. Collect. Czech. Chem. Commun.  1975,  40:  1411 

7c Č ern M. Staněk J. Pacák J. Monatsh. Chem.  1963,  94:  290 

7d Čern M. Trnka T. Buděínsk M. Collect. Czech. Chem. Commun.  1996,  61:  1489 

7e Knapp S. Myers DS. J. Org. Chem.  2001,  66:  3636 

7f Knapp S. Myers DS. J. Org. Chem.  2002,  67:  2995 

8a Driguez H. Szeja W. Synthesis  1994,  1413 

8b Ibatullin FM. Selivanov SI. Shavva AG. Synthesis  2001,  419 

9a Lindley J. Tetrahedron  1984,  40:  1433 

9b Kondo T. Mitsudo T. Chem. Rev.  2000,  100:  3205 

9c Bates CG. Gujadhur RK. Venkataraman D. Org. Lett.  2002,  4:  2803 

9d Kwong FY. Buchwald SL. Org. Lett.  2002,  4:  3517 ; and references therein

10 One example of the Cu(OAc)₂ mediated reaction of per-O-acetylated 1-thio-β-d-glucose with phenylboronic acid in refluxing DMF was reported: Herradura PS. Pendola KA. Guy RK. Org. Lett.  2000,  2:  2019 

11a Nicolaou KC. Boddy CNC. Natarajan S. Yue T.-Y. Li H. Bräse S. Ramanjulu JM. J. Am. Chem. Soc.  1997,  119:  3421 

11b Nicolaou KC. Boddy CNC. J. Am. Chem. Soc.  2002,  124:  10451 

12

General Experimental Procedure for the Preparation of 3: A degassed mixture of aryliodide 2 (1 mmol, 1 equiv), sugar thiol 1 (1.1 equiv), CuI (1 equiv), K₂CO₃ (2 equiv), and pyridine (3 equiv) was stirred in MeCN (5 mL) at 80 ºC for 24 h under Ar. After cooling, a solution of KCN (3 equiv) in water (40 mL) was added and the mixture was extracted with EtOAc (2 × 20 mL). Combined organic extracts were washed with brine, water, dried over MgSO₄ and removal of the solvent under reduced pressure followed by column chromatography on silica gel [CH₂Cl₂-(0-10%) EtOAc] afforded product 3.
3a: White solid; mp 120-121 ºC. ¹H NMR (400 MHz, CDCl₃): δ = 2.00-2.06 (br s, 4 H), 2.01 (s, 6 H), 2.03 (s, 3 H), 2.05 (s, 3 H), 3.55-3.82 (br s, 2 H), 3.78 (ddd, J = 10.0, 5.7, 2.4 Hz, 1 H), 3.82-4.02 (br s, 2 H), 4.12 (dd, J = 12.2, 2.4 Hz, 1 H), 4.22 (dd, J = 12.2, 5.7 Hz, 1 H), 5.04 (d, J = 10.1 Hz, 1 H), 5.10 (dd, J = 10.1, 9.3 Hz, 1 H), 5.16 (dd, J = 10.0, 9.3 Hz, 1 H), 5.26 (t, J = 9.3 Hz, 1 H), 7.07 (td, J = 7.6, 1.2 Hz, 1 H), 7.19 (td, J = 7.6, 1.2 Hz, 1 H), 7.38 (dd, J = 7.6, 1.2 Hz, 1 H), 7.40 (dd, J = 7.6, 1.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.55, 20.60, 20.66, 20.70, 23.71 (2 C), 46.92, 51.00, 62.32, 68.50, 70.26, 74.13, 75.57, 83.85, 117.05, 125.47, 127.48, 128.12, 129.48, 149.39, 169.25, 169.38, 170.20, 170.56. ESI-MS: m/z = 560 [M + Na]. R_f 0.22 (hexane-EtOAc, 2:1). Anal. Calcd for C₂₄H₃₁N₃O₉S: C, 53.62; H, 5.81; N, 7.82; S, 5.96. Found: C, 53.40; H, 5.89; N, 7.77; S, 5.88.
3e: Yellow solid; mp 173-174 ºC (MeOH). ¹H NMR (400 MHz, CDCl₃): δ = 1.94 (s, 3 H), 2.00 (s, 3 H), 2.02-2.13 (br s, 4 H), 2.04 (s, 3 H), 2.14 (s, 3 H), 3.6-3.8 (br s, 2 H), 3.9-4.04 (m, 4 H), 4.06-4.14 (m, 1 H), 5.08 (d, J = 10.0 Hz, 1 H), 5.10 (dd, J = 10.0, 3.4 Hz, 1 H), 5.39 (t, J = 10.0 Hz, 1 H), 5.45 (dd, J = 3.4, 0.9 Hz, 1 H), 7.45-7.52 (m, 3 H), 7.55-7.60 (m, 1 H), 7.64 (dd, J = 8.4, 1.6 Hz, 1 H), 7.75-7.80 (m, 2 H), 7.92 (d, J = 2.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.49, 20.55, 20.61, 20.78, 23.41, 23.94, 47.22, 51.32, 61.40, 67.18, 67.27, 72.01, 74.31, 83.74, 115.91, 128.18 (2 C), 129.31, 129.35, 129.68 (2 C), 130.52, 132.06, 133.98, 138.03, 151.87, 169.40, 169.99, 170.22, 170.31, 195.30. ESI-MS: m/z = 664 [M + Na]. R_f 0.62 (CH₂Cl₂-EtOAc, 7:3). Anal. Calcd for C₃₁H₃₅N₃O₁₀S: C, 58.02; H, 5.50; N, 6.55; S, 5.00. Found: C, 58.21; H, 5.62; N, 6.54; S, 5.01.

13 This compound was prepared by iodination of 4-aminobenzophenone with BTMA·ICl₂, followed by diazotization of the resulting 4-amino-3-iodobenzophenone and subsequent quenching of the diazonium salt with pyrrolidine. For the iodination protocol, see: Kajigaeshi S. Kakinami T. Yamasaki H. Fujisaki S. Okamoto T. Bull. Chem. Soc. Jpn.  1988,  61:  600 

14a Dormán G. Prestwich GD. Biochemistry  1994,  33:  5661 

14b Fleming SA. Tetrahedron  1995,  51:  12479 

15a Klapars A. Antilla JC. Huang X. Buchwald SL. J. Am. Chem. Soc.  2001,  123:  7727 

15b Klapars A. Huang X. Buchwald SL. J. Am. Chem. Soc.  2002,  124:  7421 

16 Ciattini PG. Morera E. Ortar G. Tetrahedron Lett.  1995,  36:  4133 

Multivalent carbohydrate ligands, see:

17a Mammen M. Choi S.-K. Whitesides GM. Angew. Chem. Int. Ed.  1998,  37:  2754 

17b Kitov PI. Sadowska JM. Mulvey G. Armstrong GD. Ling H. Pannu NS. Read RJ. Bundle DR. Nature (London)  2000,  403:  669 

17c Fan E. Zhang Y. Minke WE. Hou Z. Verlinde CLMJ. Hol WGJ. J. Am. Chem. Soc.  2000,  122:  2663 

18

The reactions were carried out according to the general procedure for preparation of 3 with a two-fold excess of reactants with respect to diiodotriazene 4.5a: White solid; mp 155-156 ºC (MeOH). ¹H NMR (400 MHz, CDCl₃): δ = 1.97 (s, 6 H), 2.00 (s, 6 H), 2.02-2.08 (br s, 4 H), 2.03 (s, 6 H), 2.08 (s, 6 H), 2.34 (s, 3 H), 3.52-3.79 (br s, 2 H), 3.79 (ddd, J = 10.0, 5.6, 2.3 Hz, 2 H), 3.82-4.02 (br s, 2 H), 4.14 (dd, J = 12.2, 2.3 Hz, 2 H), 4.24 (dd, J = 12.2, 5.6 Hz, 2 H), 4.80 (d, J = 10.1 Hz, 2 H), 5.05 (dd, J = 10.1, 9.3 Hz, 2 H), 5.08 (dd, J = 10.0, 9.3 Hz, 2 H), 5.23 (t, J = 9.3 Hz, 2 H), 7.23 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.53 (2 C), 20.56 (2 C), 20.64 (2 C), 20.69 (2 C), 21.35, 23.80 (2 C), 46.74, 50.94, 62.42 (2 C), 68.41 (2 C), 69.96 (2 C), 73.93 (2 C), 75.62 (2 C), 85.47 (2 C), 127.50 (2 C), 129.21 (2 C), 134.58, 146.88, 169.09 (2 C), 169.35 (2 C), 170.11 (2 C), 170.53 (2 C). ESI-MS: m/z = 936 [M + Na]. R_f 0.60 (CH₂Cl₂-EtOAc, 7:3). Anal. Calcd for C₃₉H₅₁N₃O₁₈S₂: C, 51.25; H, 5.62; N, 4.60; S, 7.02. Found: C, 51.36; H, 5.76; N, 4.53; S, 6.91.

19

Preparation of 7. The reactions of 1a with 4a to get 6 and the reaction of 6 with 1c to obtain 7 were carried out under the same conditions as for 3.
6: White solid; mp 171-172 ºC (MeOH). ¹H NMR (400 MHz, CDCl₃): δ = 1.96 (s, 3 H), 1.99 (s, 3 H), 2.01-2.11 (br s, 4 H), 2.03 (s, 3 H), 2.09 (s, 3 H), 2.29 (s, 3 H), 3.58-3.82 (br s, 2 H), 3.79 (ddd, J = 10.1, 5.7, 2.4 Hz, 1 H), 3.82-4.02 (br s, 2 H), 4.16 (dd, J = 12.3, 2.4 Hz, 1 H), 4.25 (dd, J = 12.3, 5.7 Hz, 1 H), 4.69 (d, J = 10.2 Hz, 1 H), 5.01 (dd, J = 10.2, 9.3 Hz, 1 H), 5.07 (dd, J = 10.1, 9.3 Hz, 1 H), 5.21 (t, J = 9.3 Hz, 1 H), 7.37 (dd, J = 1.8, 0.8 Hz, 1 H), 7.60 (dd, J = 1.8, 0.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.47, 20.54 (2 C), 20.61, 20.70, 23.85 (2 C), 46.94, 50.98, 62.49, 68.38, 69.90, 73.78, 75.65, 86.78, 94.35, 126.64, 131.10, 136.06, 138.43, 148.09, 169.09, 169.34, 170.05, 170.53. ESI-MS:
m/z = 700 [M + Na]. R_f 0.24 (hexane-EtOAc, 2:1). Anal. Calcd for C₂₅H₃₂IN₃O₉S: C, 44.32; H, 4.76; N, 6.20; S, 4.73. Found: C, 44.61; H, 4.86; N, 6.21; S, 4.71.
7: White solid; mp 190-191 ºC (MeOH, dec.). ¹H NMR (400 MHz, CDCl₃): δ = 1.87 (s, 3 H), 1.97 (s, 3 H), 2.00-2.06 (br s, 4 H), 2.00 (s, 3 H), 2.02 (s, 3 H), 2.028 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 2.09 (s, 3 H), 2.33 (s, 3 H), 3.40-4.00 (br, 4 H), 3.76-3.84 (m, 2 H), 4.10 (td, J = 10.4, 9.3 Hz, 1 H), 4.14 (dd, J = 12.3, 2.4 Hz, 1 H), 4.15 (dd, J = 12.4, 2.4 Hz, 1 H), 4.24 (dd, J = 12.3, 5.7 Hz, 1 H), 4.25 (dd, J = 12.4, 5.5 Hz, 1 H), 4.78 (d, J = 10.2 Hz, 1 H), 4.86 (d, J = 10.5 Hz, 1 H), 5.02 (dd, J = 10.2, 9.3 Hz, 1 H), 5.08 (app t, J = 9.6 Hz, 2 H), 5.22 (dd, J = 10.2, 9.4 Hz, 1 H), 5.23 (t, J = 9.3 Hz, 1 H), 5.63 (d, J = 9.3 Hz, 1 H), 7.22 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.52, 20.55 (2 C), 20.63, 20.67, 20.69, 20.71, 21.36, 23.20, 23.76 (2 C), 46.94, 51.13, 53.17, 62.39, 62.63, 68.33, 68.46, 69.93, 73.80, 73.93, 75.62, 75.67, 85.52, 86.04, 127.14, 128.30, 128.76, 129.11, 134.56, 146.83, 169.12, 169.29, 169.37, 169.73, 170.08, 170.53, 170.58, 170.88. ESI-MS: m/z = 935 [M + Na]. R_f 0.25 (CH₂Cl₂-EtOAc, 7:3). Anal. Calcd for C₃₉H₅₂N₄O₁₇S₂: C, 51.31; H, 5.74; N, 6.14; S, 7.02. Found: C, 51.16; H, 5.93; N, 6.00; S, 7.06.

20

8: Colorless amorphous glassy solid; mp 72-73 ºC.
¹H NMR (400 MHz, CDCl₃): δ = 1.96 (s, 3 H), 1.99 (s, 3 H), 2.13 (s, 6 H), 3.90-3.99 (m, 2 H), 4.06-4.13 (m, 1 H), 4.82 (d, J = 10.1 Hz, 1 H), 5.10 (dd, J = 10.0, 3.4 Hz, 1 H), 5.35 (t, J = 10.0 Hz, 1 H), 5.44 (dd, J = 3.4, 1.0 Hz, 1 H), 7.34 (dd, J = 8.4, 2 Hz, 1 H), 7.48-7.54 (m, 2 H), 7.59-7.63 (m, 1 H), 7.76-7.81 (m, 2 H), 7.98 (d, J = 8.4 Hz, 1 H), 8.04 (d, J = 2.4 Hz, 1 H). ESI-MS: m/z = 693 [M + Na]. R_f 0.22 (hexane-EtOAc, 2:1).