Synthetic and Structural Studies of 2‑Acylmethyl-6-R-Difunctionalized Pyridine Ligand-Containing Iron Complexes Related to [Fe]-Hydrogenase

As active site models of [Fe]-hydrogenase, tridentate 2-acylmethyl-6-methoxymethoxy-difunctionalized pyridine-containing complexes η3-(2-COCH2-6-MeOCH2OC5H3N)­Fe­(CO)2(L1) (4, L1 = I; 5, SCN; 6, PhCS2) were prepared via the following multistep reactions: (i) etherification of 2-MeO2C-6-HOC5H3N with ClCH2OMe to give 2-MeO2C-6-MeOCH2OC5H3N (1), (ii) reduction of 1 with NaBH4 to give 2-HOCH2-6-MeOCH2OC5H3N (2), (iii) esterification of 2 with 4-toluenesulfonyl chloride to give 2-TsOCH2-6-MeOCH2OC5H3N (3), (iv) nucleophilic substitution of 3 with Na2Fe­(CO)4 followed by treatment of the resulting Fe(0) intermediate Na­[(2-CH2-6-MeOCH2OC5H3N)­Fe­(CO)4] (M1) with I2 to give complex 4, and (v) condensation of 4 with KSCN and PhCS2K to give complexes 5 and 6, respectively. In contrast to the preparation of complexes 4–6, bidentate 2-acylmethyl-6-methoxymethoxy-difunctionalized pyridine-containing model complexes η2-(2-COCH2-6-MeOCH2OC5H3N)­Fe­(CO)2(I)­(L2) (7, L2 = PPh3; 8, Cy-C6H11NC) and η2-(2-COCH2-6-MeOCH2OC5H3N)­Fe­(CO)2(L3) (9, L3 = 2-SC5H4N; 10, 8-SC9H6N) were prepared by ligand exchange reactions of 4 with PPh3, Cy-C6H11NC, 2-KSC5H4N, and 8-KSC9H6N, respectively. Particularly interesting is that the tridentate 2,6-bis­(acylmethyl)­pyridine- and 2-acylmethyl-6-arylthiomethylpyridine-containing model complexes η3-[2,6-(COCH2)2C5H3N]­Fe­(CO)2(L4) (11, L4 = PPh3; 12, CO) and η3-2-(COCH2-6-ArSCH2C5H3N)­Fe­(CO)2(ArS) (13, ArS = PhS; 14, 2-S-5-MeC4H2O) were obtained, unexpectedly, when 2,6-(TsOCH2)2C5H3N reacted with Na2Fe­(CO)4 followed by treatment of the resulting mixture with ligands PPh3 and CO or disulfides (PhS)2 and (2-S-5-MeC4H2O)2. Reactions of ligand precursors 3 and 2,6-(TsOCH2)2C5H3N with Na2Fe­(CO)4 were monitored by in situ IR spectroscopy, and the possible pathways for producing complexes 4 and 11–14 via intermediates Na­[(2-CH2-6-MeOCH2OC5H3N)­Fe­(CO)4] (M1), Na­[(2-CH2-6-TsOCH2C5H3N)­Fe­(CO)4] (M2), and (2-COCH2-6-CH2C5H3N)­Fe­(CO)3 (M3) are suggested. New compounds 1–14 were characterized by elemental analysis, spectroscopy, and, for some of them, X-ray crystallography.作为[铁]-氢化酶（[Fe]-hydrogenase）的活性位点模型，三齿型含2-酰基甲基-6-甲氧基甲氧基双官能化吡啶的配合物η³-(2-COCH₂-6-MeOCH₂OC₅H₃N)Fe(CO)₂(L¹)（4，L¹=I；5，SCN；6，PhCS₂）可通过以下多步反应制备：(i) 将2-甲氧羰基-6-羟基吡啶（2-MeO₂C-6-HOC₅H₃N）与氯甲基甲醚（ClCH₂OMe）进行醚化反应，得到2-甲氧羰基-6-甲氧基甲氧基吡啶（1）；(ii) 用硼氢化钠（NaBH₄）还原化合物1，得到2-羟甲基-6-甲氧基甲氧基吡啶（2）；(iii) 将化合物2与对甲苯磺酰氯（4-toluenesulfonyl chloride）进行酯化反应，得到2-对甲苯磺酰氧基甲基-6-甲氧基甲氧基吡啶（3）；(iv) 先将化合物3与四羰基合铁酸钠（Na₂Fe(CO)₄）发生亲核取代反应，再将所得的零价铁中间体Na[(2-CH₂-6-MeOCH₂OC₅H₃N)Fe(CO)₄]（M1）用碘单质（I₂）处理，最终得到配合物4；(v) 将配合物4分别与硫氰酸钾（KSCN）和苯基二硫代甲酸钾（PhCS₂K）发生缩合反应，即可得到配合物5和6。与配合物4~6的制备路线不同，双齿型含2-酰基甲基-6-甲氧基甲氧基双官能化吡啶的模型配合物η²-(2-COCH₂-6-MeOCH₂OC₅H₃N)Fe(CO)₂(I)(L²)（7，L²=三苯基膦（PPh₃）；8，环己基异氰（Cy-C₆H₁₁NC））以及η²-(2-COCH₂-6-MeOCH₂OC₅H₃N)Fe(CO)₂(L³)（9，L³=2-吡啶硫基；10，8-喹啉硫基）可通过配合物4分别与三苯基膦（PPh₃）、环己基异氰（Cy-C₆H₁₁NC）、2-巯基吡啶钾（2-KSC₅H₄N）以及8-巯基喹啉钾（8-KSC₉H₆N）发生配体交换反应制得。尤为值得关注的是，当2,6-二对甲苯磺酰氧基甲基吡啶（2,6-(TsOCH₂)₂C₅H₃N）与四羰基合铁酸钠反应后，再分别用配体三苯基膦（PPh₃）与一氧化碳（CO），或者二硫化物二苯基二硫（(PhS)₂）与二(2-甲基-4-呋喃基)二硫（(2-S-5-MeC₄H₂O)₂）处理反应混合物时，意外得到了三齿型含2,6-双(酰基甲基)吡啶和2-酰基甲基-6-芳硫基甲基吡啶的模型配合物：η³-[2,6-(COCH₂)₂C₅H₃N]Fe(CO)₂(L⁴)（11，L⁴=三苯基膦；12，一氧化碳）以及η³-2-(COCH₂-6-ArSCH₂C₅H₃N)Fe(CO)₂(ArS)（13，ArS=苯硫基；14，2-甲基-4-呋喃硫基）。研究人员通过原位红外光谱（in situ IR spectroscopy）对配体前体3和2,6-二对甲苯磺酰氧基甲基吡啶与四羰基合铁酸钠的反应进行了原位监测，并提出了通过中间体Na[(2-CH₂-6-MeOCH₂OC₅H₃N)Fe(CO)₄]（M1）、Na[(2-CH₂-6-TsOCH₂C₅H₃N)Fe(CO)₄]（M2）以及(2-COCH₂-6-CH₂C₅H₃N)Fe(CO)₃（M3）生成配合物4及11~14的可能反应路径。所有新化合物1~14均通过元素分析、光谱学手段进行了结构表征，其中部分化合物还通过X射线单晶衍射（X-ray crystallography）确定了晶体结构。