Birch reduction of four furopyridines 1a-d effected the characteristic cleavage of the furan ring, giving ethnylpyridinols 2a-d, vinylpyridinols 3b,d, and ethylpyridinols 4a-d, and the reduction of the furan ring, giving dihydrofuropyridine 5c,d. J. Heterocyclic Chem., 39, 335 (2002).Furopyridines have a fused structure containing both a π-excess furan ring and a π-poor pyridine ring, and so, being interested in their chemical properties, we have studied the synthesis and reactions of furopyridine derivatives [1][2][3][4][5]. In this paper we report the Birch reduction of four furopyridines 1a-d.Birch reduction has been adopted for the reduction of aromatic systems, including some hetero-aromatic systems [6]. The reduction of some π-excess furans undergo a 1,4-reduction giving the corresponding 2,5-dihydrofurans. The reduction of π-poor pyridines undergo a 1,4-reduction, giving 1,4-dihydropyridines, or a cleavage of the pyridine ring, causing re-cyclization to give cyclohexenones.Four furopyridines 1a-d were subjected to Birch reduction using 3.3 equivalents of sodium metal in liquid ammonia [6], and the results are summarized in Table. As shown in Scheme 1, in the Birch reduction of furopyridines 1a-d, very interestingly, all resulted in the specific cleavage of the furan ring giving a mixture of ethynylpyridinol 2, vinylpyridinol 3, and ethylpyridinol 4. In the case of 1c and 1d, the reduction, giving dihydrofuropyridine 5c,d was also observed.Birch reduction of furo [2,3-b]pyridine (1a)[2] using 3.3 equivalents of sodium metal quantitatively gave two products, 3-ethynyl-2-pyridinol (2a) and 3-ethyl-2-pyridinol (4a) in the ratio of 1:2. Birch reduction of furo[3,2-b]pyridine (1d)[5] using 3.3 equivalents of sodium metal gave three products (in 88% total yield), 2-ethynyl-3-pyridinol (2d), 2-vinyl-3-pyridinol (3d), and 2-ethyl-3-pyridinol (4d) in the ratio of 1:2:3. Use of 1.8 equivalents of sodium metal gave four products (in 67% total yield), 2d, 3d, 4d, and 2,3-dihydro[3,2-b]pyridine (5d) in the ratio of 3:4:4:1. These results suggested that the vinyl and the dihydro derivatives are the intermediates for further reduction. Birch reduction of furo [2,3-c]pyridine (1b)[3] using 3.3 equivalents of sodium metal gave three products (in 63% total yield), 4-ethynyl-3-pyridinol (2b), 4-vinyl-3-pyridinol (3b), and 4-ethyl-3-pyridinol (4b) in the ratio of 1:2:5. Birch reduction of furo[3,2-c]pyridine (1c)[4] using 3.3 equivalents of sodium metal also gave three products (in 50% total yield), 3-ethynyl-4-pyridinol (2c), 3-ethyl-4-pyridinol (4c), and 2,3-dihydrofuro[3,2-c]pyridine (5c) in the ratio of 1:6:2.In all cases, the Birch reduction of furopyridine yielded ethynylpyridiols 2 and ethylpyridinols 4. The former ethynylpyridinols 2 were not reduction products (valenceisomerized compounds), and the latter ethylpyridinols 4 might be doubly reduced compounds. As already reported, a similar cleavage giving the correspoinding ethynylpyridinols was observed in treating 3-bromofuropyridines with alkyl lithium [7]. This sugg...
