Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation.
Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation.
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DOI：
10.3762/bjoc.7.144
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发表时间：
2011
影响因子：
2.7
通讯作者：
Robertson SD
中科院分区：
文献类型：
--
作者：
Armstrong DR;Balloch L;Hevia E;Kennedy AR;Mulvey RE;O'Hara CT;Robertson SD
在此之前，我们报道了混合金属锌酸盐试剂1((TMEDA)Na(TMP)(t-Bu)Zn(t-Bu))对N，N-二甲基苯胺的直接锌化反应令人惊讶地导致了苯胺的偏金属化(锌化)，如晶体络合物2((TMEDA)Na(TMP)(m-C6H4-NMe2)Zn(t-Bu))所示，并且这些分离的晶体的碘化定量地产生了偏异构体N，N-二甲基-3-碘苯胺。在完成研究后，我们发现，用碘处理反应溶液，转化率为72%，并产生N，N-二甲基碘苯胺的区域异构体的混合物，核磁共振测定，间异构体仍是主要产物(邻位：间位：对位比，6：73：21)。与这种双金属方法不同，N，N-二甲基苯胺与n-丁纳的盐化反应生成了二聚的邻位碱化配合物3(TMEDA)Na(o-C6H4-NMe2))2)，其结构经X-射线单晶和核磁共振表征。在反应溶液中没有观察到区域异构体。在该反应溶液中引入t-Bu2Zn得到了固相共晶产物，由双芳胺4((TMEDA)Na(o-C6H4-NMe2)2ZN(t-Bu))和Me2N-C裂解产物5({(TMEDA)2Na}+{(t-Bu2Zn)2(µ-NMe2)}−)组成。对生成4和5的反应混合物的核磁共振研究表明，生成4和5的反应混合物中增加了一个物种，但混合物作为一个整体只含有碘猝灭所确定的正位物种和微量的对位物种。在双金属反应的一个间接变化中，在室温下将TMP(H)加到反应混合物中，得到4和5。这得到了晶体产物6((TMEDA)Na(TMP)(o-C6H4-NMe2)Zn(t-Bu))，根据X-射线晶体和核磁共振数据确定了金属配合物2的邻位异构体。用碘化法监测反应的区域选择性，发现邻位：间位：对位的比率为16.6：1.6：1.0。有趣的是，当含有TMP(H)的溶液在回流下加热18h时，产生了更多的偏异构体(对应的比例为3.7：4.2：1.0)。这种变化很可能起源于一种回溯反应，该反应产生了作为中间体的原始碱基1。用B3LYP方法和6-311G**基组在密度泛函水平上进行了理论计算，探讨了单金属和双金属体系的能级。与实验结果一致的是，钠化有利于原金属化，而钠介导锌化有利于偏金属化(紧随其后)。
Previously we reported that direct zincation of N,N-dimethylaniline by the mixed-metal zincate reagent 1 ((TMEDA)Na(TMP)(t-Bu)Zn(t-Bu)) surprisingly led to meta-metallation (zincation) of the aniline, as manifested in the crystalline complex 2 ((TMEDA)Na(TMP)(m-C6H4-NMe2)Zn(t-Bu)), and that iodination of these isolated crystals produced the meta-isomer N,N-dimethyl-3-iodoaniline quantitatively. Completing the study here we find that treating the reaction solution with iodine produces a 72% conversion and results in a mixture of regioisomers of N,N-dimethyliodoaniline, with the meta-isomer still the major product (ortho:meta:para ratio, 6:73:21), as determined by NMR. In contrast to this bimetallic method, sodiation of N,N-dimethylaniline with n-BuNa produced the dimeric, ortho-sodiated complex 3 (((TMEDA)Na(o-C6H4-NMe2))2), as characterised by X-ray crystallography and NMR. No regioisomers were observed in the reaction solution. Introducing t-Bu2Zn to this reaction solution afforded a cocrystalline product in the solid-state, composed of the bis-anilide 4 ((TMEDA)Na(o-C6H4-NMe2)2Zn(t-Bu)) and the Me2N–C cleavage product 5 ({(TMEDA)2Na}+{(t-Bu2Zn)2(µ-NMe2)}−), which was characterised by X-ray crystallography. NMR studies of the reaction mixture that produces 4 and 5 revealed one additional species, but the mixture as a whole contained only ortho-species and a trace amount of para-species as established by iodine quenching. In an indirect variation of the bimetallic reaction, TMP(H) was added at room temperature to the reaction mixture that afforded 4 and 5. This gave the crystalline product 6 ((TMEDA)Na(TMP)(o-C6H4-NMe2)Zn(t-Bu)), the ortho-isomer of the meta-complex 2, as determined from X-ray crystallographic and NMR data. Monitoring the regioselectivity of the reaction by iodination revealed a 16.6:1.6:1.0 ortho:meta:para ratio. Interestingly, when the TMP(H) containing solution was heated under reflux for 18 hours more meta-isomer was produced (corresponding ratio 3.7:4.2:1.0). It is likely that this change has its origin in a retro reaction that produces the original base 1 as an intermediate. Theoretical calculations at the DFT level using the B3LYP method and the 6-311G** basis set were used to probe the energetics of both monometallic and bimetallic systems. In accord with the experimental results, it was found that ortho-metallation was favoured by sodiation; whereas meta- (closely followed by para-) metallation was favoured by direct sodium-mediated zincation.
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影响因子：
15
作者：
BROADDUS, CD
通讯作者：
BROADDUS, CD
影响因子：
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作者：
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作者：
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