Fluorous Boc ((F)Boc) carbamates: New amine protecting groups for use in fluorous synthesis

The first fluorous variants of the Boc (tert-butyloxycarbonyl) group have b een prepared and tested for their suitability as nitrogen protecting groups . A group with two fluorous chains and an ethylene spacer, (RfCH(2)CH(2))(2 )(CH3)COC(O)-, was readily attached to a representative amine but was diffi cult to cleave. In contrast, groups with two fluorous chains and a propylen e spacer, (RfCH(2)CH(2)CH(2))(2)-(CH3)COC(O)-, or one fluorous chain and an ethylene spacer, (RfCH(2)CH(2))(CH3)(2)COC(O)-, were readily formed and cl eaved. The fluorous alcohol component of the (F)Boc group can be removed by evaporation and can be recovered and reused. The utility of the new (F)Boc group (C8F17CH2-CH2)(CH3)(2)COC(O)- was demonstrated in 16 and 96 compound library synthesis exercises. Separations can be achieved either by manual, parallel fluorous solid-phase extraction, or automated, serial fluorous ch romatography. The results provide additional confirmation of the value of " light" fluorous synthesis techniques, and the new fluorous Boc groups expan d the applicability of fluorous synthesis techniques to many classes of nit rogen-containing organic compounds.