Institut für Organische Chemie, Universität Regensburg, Universitätsstr. 31, D-93053 Regensburg, Germany.
J Org Chem. 2011 May 6;76(9):3005-15. doi: 10.1021/jo200431v. Epub 2011 Mar 29.
The proline-catalyzed self-condensation of aliphatic aldehydes in DMSO with varying amounts of catalyst was studied by in situ NMR spectroscopy. The reaction profiles and intermediates observed as well as deuteration studies reveal that the proline-catalyzed aldol addition and condensation are competing, but not consecutive, reaction pathways. In addition, the rate-determining step of the condensation is suggested to be the C-C bond formation. Our findings indicate the involvement of two catalyst molecules in the C-C bond formation of the aldol condensation, presumably by the activation of both the aldol acceptor and donor in a Mannich-type pathway. This mechanism is shown to be operative also in the oligomerization of acetaldehyde with high proline amounts, for which the first in situ detection of a proline-derived dienamine was accomplished. In addition, the diastereoselectivity of the aldol addition is evidenced to be time-dependent since it is undermined by the retro-aldolization and the competing irreversible aldol condensation; here NMR reaction profiles can be used as a tool for reaction optimization.
通过原位 NMR 光谱法研究了在 DMSO 中不同量催化剂条件下脂肪醛的脯氨酸催化自缩合反应。观察到的反应曲线和中间体以及氘代研究表明，脯氨酸催化的羟醛加成和缩合是竞争的，但不是连续的反应途径。此外，推测缩合的速率决定步骤是 C-C 键形成。我们的研究结果表明，两个催化剂分子参与了羟醛缩合的 C-C 键形成，可能是通过曼尼希型途径激活了羟醛接受体和供体。该机理在高脯氨酸用量下乙醛的齐聚反应中也适用，首次在原位检测到脯氨酸衍生的烯胺。此外，由于反羟醛化和竞争的不可逆羟醛缩合，羟醛加成的非对映选择性被证明是时间依赖性的；在这里，NMR 反应曲线可以用作反应优化的工具。
