Enantio- and Diastereoselective Formal Hetero-Diels-Alder Reactions of Trifluoromethylated Enones Catalyzed by Chiral Primary Amines.
Enantio- and Diastereoselective Formal Hetero-Diels-Alder Reactions of Trifluoromethylated Enones Catalyzed by Chiral Primary Amines.
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DOI：
10.1002/chem.201501897
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Yongjun Lin;L. Du;Tairan Kang;Quan-Zhong Liu;Zeqin Chen;Long He
中科院分区：
文献类型：
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作者：
Yongjun Lin;L. Du;Tairan Kang;Quan-Zhong Liu;Zeqin Chen;Long He
报道了由脂肪族无环烯酮和手性伯胺原位生成的三氟甲基烯酮和2-氨基-1，3-丁二烯的不对称形式的Diels-Alder反应。相应的四氢吡喃-4-酮以高达94%的产率和高达94%的ee形成。反应通过分步反应进行，包括2-氨基-1，3-丁二烯在氨基催化下缩合成三氟甲基化的羰基，然后进行分子内的oxa-Michael加成反应。核磁共振研究和过渡态理论计算表明，质子化的叔胺能同时通过N-H⋅⋅⋅F和N-H⋅⋅⋅O的氢键作用，有效地激活三氟甲基酮的羰基，促进加成过程，从而为氨基-1，3-丁二烯接近活化的三氟甲基酮提供了手性环境，从而获得了高的对映选择性。
Enantioselective formal hetero-Diels-Alder reactions of trifluoromethylated enones and 2-amino-1,3-butadienes generated in situ from aliphatic acyclic enones and chiral primary amines are reported. The corresponding tetrahydropyran-4-ones are formed in up to 94 % yield and with up to 94 % ee. The reaction was carried out through a stepwise mechanism, including initial aminocatalytic aldol condensation of 2-amino-1,3-butadiene to the trifluoromethylated carbonyl group followed by an intramolecular oxa-Michael addition. Both NMR investigation and theoretical calculations on the transition state indicate that the protonated tertiary amine could effectively activate the carbonyl group of the trifluoromethyl ketone to promote the addition process through hydrogen-bonding interaction of N-H⋅⋅⋅F and N-H⋅⋅⋅O simultaneously, and thus provide a chiral environment for the approach of amino-1,3-butadienes to the activated trifluoromethyl ketone, resulting in high enantioselectivity.