Several convenient methods for the synthesis of 2-amido substituted furans.
Several new methods for the synthesis of differently substituted 2-amidofurans are described. The thermolysis of furan-2-carbonyl azide results in a Curtius rearrangement and the resulting furanyl isocyanate was trapped with various organometallic reagents. A second method consists of a C-N cross-coupling reaction of a bromo-substituted furan with various amides, carbamates, and lactams. The CuI-catalyzed cross-coupling reaction between furanyl bromides and amides furnished 2- and 3-substituted amidofurans in 45-95% yield. The third protocol used involves the reaction of cyclic carbinol amides with triflic anhydride. The reaction proceeds under very mild conditions to provide alpha-(trifluoromethyl)sulfonamido-substituted furans in high yield. The resulting iminium ion derived from the reaction of the hydroxy pyrrolidinone with Tf(2)O undergoes a facile ring opening as a consequence of the adjacent hydroxyl group to produce an imino triflate intermediate. Subsequent cyclization of this highly electrophilic imine with the oxygen atom of the adjacent carbonyl group leads to an imino dihydrofuran that reacts further with another equivalent of Tf(2)O to give the observed product.
Padwa
Albert
A
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA. chemap@emory.edu
Crawford
Kenneth R
KR
Rashatasakhon
Paitoon
P
Rose
Mickea
M
D000577:Amides / Q000032:analysis / Q000138:chemical synthesis*; D002219:Carbamates / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D005663:Furans / Q000032:analysis / Q000138:chemical synthesis*; D007454:Iodides / Q000737:chemistry; D017953:Isocyanates / Q000737:chemistry; D007769:Lactams / Q000737:chemistry; D015394:Molecular Structure; D013696:Temperature
D000577:Amides; D002219:Carbamates; D005663:Furans; D007454:Iodides; D017953:Isocyanates; D007769:Lactams; D003300:Copper