Structure Dependence in Asymmetric Deprotonative Fluorination and Fluorocyclization Reactions of Allylamine Derivatives with Linked Binaphthyl Dicarboxylate Phase-Transfer Catalyst
Structure Dependence in Asymmetric Deprotonative Fluorination and Fluorocyclization Reactions of Allylamine Derivatives with Linked Binaphthyl Dicarboxylate Phase-Transfer Catalyst
复制标题
烯丙胺衍生物与联萘二甲酸相转移催化剂的不对称去质子氟化和氟环化反应中的结构依赖性
DOI：
10.1021/jacs.1c06783
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发表时间：
2021
影响因子：
15
通讯作者：
Hamashima Yoshitaka
中科院分区：
文献类型：
--
作者：
Niwa Tomoki;Nishibashi Kousuke;Sato Hitomi;Ujiie Kiyoshi;Yamashita Kenji;Egami Hiromichi;Hamashima Yoshitaka
γ，γ-二取代的烯丙基胺衍生物（例如，3，7，和8）进行了研究，使用我们的双阴离子相转移催化剂。根据烯烃部分上的取代基，反应以高度对映选择性的方式（高达99%ee）提供手性烯丙基氟化物和氟化二氢恶嗪。发现这些产物的绝对立体化学与我们先前报道的γ-单取代烯丙基酰胺的氟环化（例如，13和14）。为了探索这一有趣的现象，我们通过NMR实验和动力学研究，研究了烯烃部分的取代模式对反应的影响。γ，γ-双取代底物的去质子化和氟环化反应速率律为v =k[cat]0.6，而γ-单取代底物的氟环化反应速率律为v =k[底物][cat]0.4。小于1的指数表明催化剂离子对的聚集态参与催化循环。有趣的是，在γ，γ-双取代底物的反应中观察到正的非线性效应，而在γ-单取代底物的情况下观察到负的非线性效应。因此，反应途径取决于在底物的γ位上存在或不存在烷基取代基，并且基于我们的机理研究，我们提出γ，γ-二取代底物的活性催化物种是催化剂离子对聚集体，而γ-单取代底物的活性催化物种是活性更高的单体催化剂离子对物种，即使其浓度较低。
The asymmetric fluorofunctionalization of γ,γ-disubstituted allylamine derivatives (e.g.,3,7, and8) was investigated using our dianionic phase-transfer catalyst. Depending on the substituents on the alkene moiety, the reaction afforded chiral allylic fluorides and fluorinated dihydrooxazines in a highly enantioselective manner (up to 99% ee). The absolute stereochemistry of these products was found to be opposite to that in our previously reported fluorocyclization of γ-monosubstituted allylic amides (e.g.,13and14). To probe this interesting phenomenon, we investigated the influence of the substitution pattern of the alkene moiety on the reaction by means of NMR experiments and kinetic studies. The rate laws of the deprotonative fluorination and the fluorocyclization of γ,γ-disubstituted substrates werev=k[cat]0.6, while that of the fluorocyclization of γ-monosubstituted substrates wasv=k[substrate][cat]0.4. An exponent of less than 1 suggests the involvement of an aggregated state of the catalyst ion pair in the catalytic cycle. Interestingly, a positive nonlinear effect was observed in the reactions of the γ,γ-disubstituted substrates, while a negative nonlinear effect was observed in the case of the γ-monosubstituted substrates. Thus, the reaction pathway depends on the presence or absence of an alkyl substituent at the γ position of the substrates, and on the basis of our mechanistic studies we propose that the active catalytic species for γ,γ-disubstituted substrates is a catalyst ion pair aggregate, whereas that for γ-monosubstituted substrates is the more active monomeric catalyst ion pair species, even though its concentration would be low.