- A ring expansion strategy towards diverse azaheterocycles
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The development of innovative strategies for the synthesis of N-heterocyclic compounds is an important topic in organic synthesis. Ring expansion methods to form large N-heterocycles often involve the cycloaddition of strained aza rings with π bonds. However, in some cases such strategies suffer from some limitations owing to the difficulties in controlling the regioselectivity and the accessibility of specific π-bond synthons. Here, we report the development of a general ring expansion strategy that involves a formal cross-dimerization between three-membered aza heterocycles and three- and four-membered-ring ketones through synergistic bimetallic catalysis. These formal cross-dimerizations of two different strained rings are efficient and scalable, and provide a straightforward and broadly applicable means of assembling diverse N-heterocycles, such as 3-benzazepinones, dihydropyridinones and uracils, which are versatile units in numerous drugs and biologically active compounds. Preliminary mechanistic studies revealed that the C–C bond of strained ring ketones is first cleaved by the Pd0 species during the reaction. [Figure not available: see fulltext.].
- Li, Ruirui,Li, Bo,Zhang, Hongpeng,Ju, Cheng-Wei,Qin, Ying,Xue, Xiao-Song,Zhao, Dongbing
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p. 1006 - 1016
(2021/07/25)
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- Synthesis and structure/NMDA receptor affinity relationships of 1-substituted tetrahydro-3-benzazepines
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A novel synthesis of 1-substituted tetrahydro-1H-3-benzazepines 4 is described. Starting with (2-bromophenyl)acetaldehyde acetal 5, the nitrostyrene 9 was prepared in three steps allowing the addition of various nucleophiles to yield the nitroacetals 10.
- Krull, Olaf,Wuensch, Bernhard
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p. 1439 - 1451
(2007/10/03)
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- Noncompetitive NMDA Antagonists: A novel synthesis of 1-phenyltetrahydro-3-benzazepines
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The key step in the synthesis of the pharmacologically interesting l-phenyltetrahydro-3-benzazepine skeleton is the Michael addition of (2-lithiophenyl)acetaldehyde acetals, which are generated in situ upon treatment of the bromo acetals 5a,b with n-butyllithium, to β-nitrostyrene (6). The reductive ring closure of the nitro acetals 7a,b succeeded with zinc dust and hydrochloric acid to give the 3-benzazepines 11a,b in good yields. The unsubstituted 3-benzazepine 11a showed a considerable affinity for the phencyclidine binding site of the NMDA receptor (K(i) = 6.41 μM), whereas donor substituents in the aryl moiety (11b,c) reduce the affinity for the NMDA receptor.
- Wuensch, Bernhard,Nerdinger, Sven,Bauschke, Gerd,Hoefner, Georg
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p. 211 - 214
(2007/10/03)
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