Methylprenyl and Prenyl Protection for Sulfonamides

Dedicated to Dr. Valerjans Kauss on the occasion of his 60^th birthday

Abstract

2-Methylprenyl (MePre) is an efficient protection for sulfonamides. The acidic cleavage of this group leads to volatile by-products and the product can be obtained in high purity without additional purification. MePre group is resistant to Pd/C-catalysed hydrogenolysis at 1 atm, Suzuki–Miyaura reaction, Ni(0) catalysis conditions and oxidising reagents such as NIS and DDQ. The prenyl (Pre) group can also be used to protect sulfonamides in certain cases; however, the substrate scope is limited due to the side product formation.

Key words

sulfonamides - protecting groups - allylation - cations - cleavage

• References and Notes

• 1 Supuran CT, Casini A, Scozzafava A. Med. Res. Rev. 2003; 23: 535
• 2 Supuran CT, Innocenti A, Mastrolorenzo A, Scozzafava A. Mini-Rev. Med. Chem. 2004; 4: 189
• 3 Graham SL, Scholz TH. J. Org. Chem. 1991; 56: 4260
• 4 Wan Y, Wu X, Kannan MA, Alterman M. Tetrahedron Lett. 2003; 44: 4523
• 5 Mahalingam AK, Wu X, Wan Y, Alterman M. Synth. Commun. 2005; 35: 417
• 6 Burlingham BT, Widlanski TS. J. Am. Chem. Soc. 2001; 123: 2937
• 7 Johnson DC. II, Widlanski TS. Tetrahedron Lett. 2004; 45: 8483
• 8 Poss MA, Reid JA. Tetrahedron Lett. 1992; 33: 7291
• 9 Morris J, Wishka DG. J. Org. Chem. 1991; 56: 3549
• 10 Hill B, Liu Y, Taylor SD. Org. Lett. 2004; 6: 4285
• 11 Videnov G, Aleksiev B, Stoev M, Paipanova T, Jung G. Liebigs Ann. Chem. 1993; 1993: 941
• 12 Alonso E, Ramón DJ, Yus M. Tetrahedron 1997; 53: 14355
• 13 Taniguchi T, Ogasawara K. Tetrahedron Lett. 1998; 39: 4679
• 14 Sharma GV. M, Ilangovan A, Mahalingam AK. J. Org. Chem. 1998; 63: 9103
• 15 Sharma GV. M, Reddy CG, Krishna PR. Synlett 2003; 11: 1728
• 16 Narender T, Venkateswarlu K, Madhur G, Reddy KP. Synth. Commun. 2012; 43: 26
• 17 Vatèle J.-M. Tetrahedron 2002; 58: 5689
• 18 Tsuritani T, Shinokubo H, Oshima K. Tetrahedron Lett. 1999; 40: 8121
• 19 Babu KS, Raju BC, Srinivas PV, Rao AS, Kumar SP, Rao JD. Chem. Lett. 2003; 32: 704
• 20 Marković D, Vogel P. Org. Lett. 2004; 6: 2693
• 21 Nikitjuka A, Jirgensons A. Synlett 2012; 23: 2972
• 22 Löber O, Kawatsura M, Hartwig JF. J. Am. Chem. Soc. 2001; 123: 4366
• 23 General Procedure for the Cleavage of MePre Group in 1: To a stirred solution of protected sulfonamide 1 (0.15 mmol) in CH₂Cl₂ (0.75 mL) were added triethylsilane (75 μL) and TFA (75 μL, 10 vol%). The reaction mixture was stirred at r.t. until full conversion of the starting material was observed (see Table 1). The solvent was removed in vacuo and the residue was diluted with Et₂O and the solvent was then evaporated. Dilution and evaporation was repeated twice more to give the deprotected sulfonamide.
• 24 Mayr H, Foerner W, von Rague Schleyer P. J. Am. Chem. Soc. 1979; 101: 6032