Probing α-Amino Aldehydes as Weakly Acidic Pronucleophiles: Direct Access to Quaternary α-Amino Aldehydes by an Enantioselective Michael Addition Catalyzed by Bronsted Bases
Probing α-Amino Aldehydes as Weakly Acidic Pronucleophiles: Direct Access to Quaternary α-Amino Aldehydes by an Enantioselective Michael Addition Catalyzed by Bronsted Bases
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DOI：
10.1002/chem.202004468
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发表时间：
2020-12-23
影响因子：
4.3
通讯作者：
Palomo, Claudio
中科院分区：
文献类型：
--
作者：
Garcia-Urricelqui, Ane;de Cozar, Abel;Palomo, Claudio
α -氨基醛发生1,2加成的高倾向及其在碱性条件下相对较低的稳定性在很大程度上阻碍了它们作为亲核试剂在不对称催化领域的应用，特别是在生产季α -氨基醛方面。本文通过记录α -支链α -氨基醛与硝基烯烃的第一次直接α -烷基化反应，证明了α -氨基醛的化学反应可能超出这些限制。该反应产生密集功能化的产物，具有高的非映体和对映体选择性，多达两个，季和叔，邻立体中心。DFT模型提出，起始α -氨基醛中NH基团与羰基氧原子之间的分子内氢键是反应立体控制的关键。
The high tendency of alpha-amino aldehydes to undergo 1,2-additions and their relatively low stability under basic conditions have largely prevented their use as pronucleophiles in the realm of asymmetric catalysis, particularly for the production of quaternary alpha-amino aldehydes. Herein, it is demonstrated that the chemistry of alpha-amino aldehydes may be expanded beyond these limits by documenting the first direct alpha-alkylation of alpha-branched alpha-amino aldehydes with nitroolefins. The reaction produces densely functionalized products bearing up to two, quaternary and tertiary, vicinal stereocenters with high diastereo- and enantioselectivity. DFT modeling leads to the proposal that intramolecular hydrogen bonding between the NH group and the carbonyl oxygen atom in the starting alpha-amino aldehyde is key for reaction stereocontrol.