Furopyridines. XXXI. Birch reduction of furopyridines

Abstract

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...

Enantioselectivity in visible light-induced, singlet oxygen [2+4] cycloaddition reactions (type II photooxygenations) of 2-pyridones

“…When applying the reaction conditions to other 2-pyridones, we noted varying yields and enantioselectivities (Table 2). With 3-ethyl-2-pyridone (9) 16 the reaction sequence worked -as expected given its similarity to 3 -in the same yield (entry 1) and with similar enantioselectivity for the final product 10 (86% ee). In the case of the benzyl-substituted substrate 11 17 (entry 2) a significant decrease in chemo-and enantioselectivity was noted.…”

“…The assignment of the absolute configuration for the respective major enantiomers as depicted in Table 2 is based on analogy to the transformation 3 -6. Indeed, all products (6, 10, 12, 14, 16,18) have been shown to be consistently levorotatory indicating that the major enantiomers possess identical absolute configurations. The chiral template remained unaffected by singlet oxygen and was recovered chromatographically in yields between 80-90%.…”