Fused phenanthridines: domino cyclization of 1,6-diynes with bromo(iso)quinoline.
Fused phenanthridines: domino cyclization of 1,6-diynes with bromo(iso)quinoline.
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DOI：
10.1002/asia.201000692
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发表时间：
2011-03
期刊：
影响因子：
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通讯作者：
Yimin Hu;Yongjie Sun;Jiping Hu;T. Zhu;Tao Yu;Quansheng Zhao
中科院分区：
文献类型：
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作者：
Yimin Hu;Yongjie Sun;Jiping Hu;T. Zhu;Tao Yu;Quansheng Zhao
Fused phenanthridines are an important class of heterocycles that show a broad range of biological and pharmaceutical activity.[1] These structural motifs are found in a plethora of different natural products (Scheme 1).[2] Molecules containing phenanthridine are the subject of considerable interest as potent antitumor, antimicrobial, and antiviral agents.[3] Therefore, numerous synthetic strategies for the preparation of these scaffolds have been developed.[4] Recently, Cronin and co-workers [5] developed a new CÀC bond-forming annulation reaction leading to a class of 2, 3-dihydro-12H-pyrrolo-ACHTUNGTRENNUNG [1, 2-f] phenanthridine derivatives that exhibit a reversible “lockable molecular switch”/ring-opening-cyclization process. Lautens and co-workers have reported a powerful strategy for the synthesis of diversely substituted phenanthridines and benzo [c] phenanthridines involving a sequence of domino ortho-functionalization with palladium-catalyzed cross-coupling processes.[6] Much effort has been invested in synthesizing the derivatives of these phenanthridines to deduce structure–activity relationships and discover new analogues with improved properties.[7–9] Notably, Yu and coworkers reported the first example of directed transitionmetal-catalyzed CÀH functionalizations of a pyridine ring at the 3-or 4-position.[10] Our group has also employed a domino strategy to devise alternative processes for the efficient construction of benzocyclo [penta-to octa-] isoindole.[11] We envisioned a CÀH activation/cross-coupling approach toward the synthesis of diversely polycyclic phenanthridine derivatives (Scheme 1). This cascade series consists of interand intramolecular Heck reactions and a subsequent regioselective direct arylation by CÀH activation of the quinoline ring at the 2-or 4-positions. Herein, we report the palladium-catalyzed domino reactions of dimethyl 2, 2-bis (3-phenylprop-2-ynyl) malonate (1a), diethyl 2, 2-bis (3-phenylprop-2-ynyl) malonate (1b), 1-ethyl 3-methyl 2, 2-bis (3-phenylprop-2-ynyl) malonate (1c), dimethyl 2, 2-bis (3-(4-chlorophenyl)-prop-2-ynyl) malonate (1d), diethyl 2, 2-bis (3-(4-chlorophenyl) prop-2-ynyl) malonate (1e), 1-ethyl 3-methyl 2, 2-bis (3-(4-chlorophenyl) prop-2-ynyl) malonate (1 f), dimethyl 2, 2-bis (3-p-tolylprop-2-ynyl) malonate (1g), diethyl 2, 2-bis (3-ptolylprop-2-ynyl) malonate (1h), diethyl 2, 2-bis (3-(4-methoxyphenyl) prop-2-ynyl) malonate (1i), diethyl 2, 2-bis (3-(4-fluorophenyl) prop-2-yn-1-yl) malonate (1j), and dimethyl 2, 2-bis (3-(4-fluorophenyl) prop-2-yn-1-yl) malonate (1k) with 3-bromoACHTUNGTRENNUNG (iso) quinoline or 3-bromopyridine, in the direct, efficient, and economic construction of phenanthridine and quinoline through both CÀC bond coupling and CÀH bond activation. Optimization of the reaction conditions was performed using diethyl 2, 2-bis (3-(4-chlorophenyl) prop-2-ynyl)-malonate (1e) and 3-bromoquinoline (Table 1). Reaction of 1e with 3-bromoquinoline in N, N-dimethylformamide
