Evaluating cis-2,6-dimethylpiperidide (cis-DMP) as a base component in lithium-mediated zincation chemistry.
Evaluating cis-2,6-dimethylpiperidide (cis-DMP) as a base component in lithium-mediated zincation chemistry.
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DOI：
10.1002/chem.201301180
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发表时间：
2013-09-27
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影响因子：
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通讯作者：
Steven A
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文献类型：
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作者：
Armstrong DR;Garden JA;Kennedy AR;Leenhouts SM;Mulvey RE;O'Keefe P;O'Hara CT;Steven A
金属化合物化学的最新进展集中在混合金属（通常为酸盐）组合物中的大体积仲酰胺2，2，6，6-四甲基哌啶（TMP）上。然而，前体胺TMP（H）相当昂贵，因此更便宜的替代品将是受欢迎的。因此，本研究旨在开发更便宜的非TMP基混合金属碱，并选择顺式-2，6-二甲基哌啶（cis-diperidide）作为替代酰胺，开发顺式-diperidide锌酸盐化学，与其富甲基对应物TMP相比，其受到的关注很少。通过Li（cis-Zn）、Et 2 Zn和TMEDA的共络合反应，合成了一种新的二乙基锌酸锂[（TMEDA）LiZn（cis-Zn）Et 2]（TMEDA=N，N，N′，N′-四甲基乙二胺），并通过NMR（包括DOSY）和X射线晶体学进行了表征。通过使用N，N-二异丙基苯甲酰胺作为测试芳族底物，[（TMEDA）LiZn（cis-Zn）Et 2]的去质子化反应性已被探测并与已知的但先前未研究的二叔丁基锌酸盐[（TMEDA）LiZn（cis-Zn）tBu 2]的去质子化反应性进行对比。发现前者是较好的上级碱（例如，在锌化苯甲酰胺中间体的D2 O淬灭之后，以78%和48%的相应产率产生邻氘化产物）。通过两当量的二乙基锌酸酯与苯甲酰胺反应，然后碘化，得到88%产率的2-碘-N，N-二异丙基苯甲酰胺。还绘制了使用1，1，1，3，3，3-六甲基二硅基氨基化物（HMDS）、二异丙基酰胺和TMP作为氨基锂、Et 2 Zn和TMEDA体系中的氨基组分的比较。在某些条件下，发现顺式-异丙基碱系统与HMDS和二异丙基酰胺（DA）相比给出改进的结果，并且与TMP系统相当的结果。从二叔丁基锌酸盐的反应中分离出两种新的配合物，即前金属配合物[{（iPr）2N（Ph）C=O}LiZn（cis-Zn）tBu 2]和后金属配合物[（TMEDA）Li（cis-Zn）{2-[1-C（=O）N（iPr）2] C6 H4}Zn（tBu）]，并对其进行了晶体学表征，揭示了这些碱金属介导的锌化反应的结构和机理。这些反应的各个方面也通过DFT计算建模。
Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis-DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry which has received meagre attention compared to that of its methyl-rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2] (TMEDA=N,N,N′,N′-tetramethylethylenediamine) has been synthesised by co-complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di-tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho-deuteriated product in respective yields of 78 % and 48 % following D2O quenching of zincated benzamide intermediates). An 88 % yield of 2-iodo-N,N-diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di-tert-butylzincate and crystallographically characterised, namely the pre-metallation complex [{(iPr)2N(Ph)C=O}LiZn(cis-DMP)tBu2] and the post-metallation complex [(TMEDA)Li(cis-DMP){2-[1-C(=O)N(iPr)2]C6H4}Zn(tBu)], shed valuable light on the structures and mechanisms involved in these alkali-metal-mediated zincation reactions. Aspects of these reactions are also modelled by DFT calculations.