Development of novel synthetic method for beta-substituted pyrroles

β-取代的吡咯广泛存在于生物活性化合物如抗生素中，但这类化合物很难通过吡咯的常规亲电取代反应获得。本研究旨在发展一种以分子氮为氮源合成β-取代吡咯的新方法。肼基（2-）配合物trans-[MX（NNH_2）（dppe）_2]^+（M=Mo，W ; X=F，CL ; dppe=ph_2PCH_2CH_2PPh_2）和cis，mer-[WX_2（NNH_2）（PMe_2Ph）_3]（X=Cl，Br）与2缩合，得到反式-[M（N_2）_2（dppe）_2]（1）和顺式-[W（N_2）_2（PMe_2Ph）_4]，5-二甲氧基四氢呋喃反应，分别得到反式-[MX（NNCH=CHCH=CH）（dppe）_2]^+（2^+）和顺式，mer-[WX_2（NNCH=CHCH=CH）（PMe_2Ph）_3（3）类型的吡咯亚胺配合物。其结构经光谱表征，并经X射线衍射研究进一步证实。配合物2^+中吡咯环上的亲电取代反应 关于我们 选择性地发生在β-位，得到相应的β-取代的吡咯酰亚胺配合物反式-[MX（NNCH=C（E）CH=CH）（dppe）_2]^+（E=Br，CN，SO_3 ^-，COR），虽然2^+与N-氯代琥珀酰亚胺在THF中的氯化反应主要发生在α-位，但这种β-区域选择性与游离吡咯的α-区域选择性形成鲜明对比，并且可能由DPPE配体的空间效应引起。配合物2^+在室温条件下用LiAlH_4容易地还原，以高产率释放吡咯和N-氨基吡咯。此外，在还原之后，可以以中等产率回收可以转化回原始双氮络合物1的四氮杂环配合物[MHH_4（dppe）_4]。这完成了从二氮络合物1开始的吡咯和N-氨基吡咯的合成循环。以2a^+（M=W，X=Cl）为起始原料，通过β-选择性庚酰化反应，然后用LiAlH_4还原，制备了β-庚基吡咯。3a（X=Br）用LiAlH_4还原主要生成吡咯，而3a用KOH/EtOH处理则高产率地生成N-氨基吡咯。少

beta-Substituted pyrroles are widely found in biologically active compounds such as antibiotics, but this class of compounds can hardly be obtained by the conventional electrophilic substitution reactions of pyrrole. This research project aims at developing a novel synthetic method for beta-substituted pyrroles by utilizing molecular nitrogen as the nitrogen source.Hydrazido (2-) complexes trans-[MX (NNH_2)(dppe)_2]^+ (M=Mo, W ; X=F,CL ; dppe=ph_2PCH_2CH_2PPh_2) and cis, mer-[WX_2 (NNH_2)(PMe_2Ph)_3](X=Cl, Br), which are readily derived from trans-[M (N_2)_2 (dppe)_2](1) and cis-[W (N_2)_2 (PMe_2Ph)_4]by protonation, condensed with 2,5-dimethoxytetrahydrofuran to afford pyrrolylimido complexes of the type trans-[MX (NNCH=CHCH=CH)(dppe)_2]^+ (2^+) and cis, mer-[WX_2 (NNCH=CHCH=CH)(PMe_2Ph)_3 (3), respectively. Their structures were characterized spectroscopically, and further confirmed by X-ray diffraction study. Electrophilic substitution reactions at the pyrrole ring in complexes 2^+ … More occurred selectively at the beta-position to give the corresponding beta-substituted pyrrolylimido complexes trans-[MX (NNCH=C (E) CH=CH)(dppe)_2]^+ (E=Br, CN,SO_3^-, COR), although only chlorination of 2^+ with N-chlorosuccinimide in THF took place predominantly at the alpha-position, This beta-regioselectivity is in sharp contrast to the alpha-regioselectivity of free pyrrole, and is probably caused by the steric effect of the dppe ligands. Complexes 2^+ were readily reduced under ambient conditions with LiAlH_4 to liberate pyrrole and N-aminopyrrole in high yields. Further, the tetrahydrido complexes [MHH_4 (dppe)_4], which can be converted back into the original dinitrogen complexes 1, were recovered in moderate yields after the reduction. This accomplishes the synthetic cycle for pyrrole and N-aminopyrrole starting from the dinitrogen complexes 1. beta-Heptylpyrrole was also prepared starting from 2a^+ (M=W,X=Cl) by the beta-selective heptanoylation followed by the reduction with LiAlH_4. On the other hand, reduction of 3a (X=Br) with LiAlH_4 predominantly produced pyrrole, whereas treatment of 3a with KOH/EtOH liberated N-aminopyrrole in a high yield. Less