The mechanism of the enantioselective ring-opening aminolysis of 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane with benzylamine, catalyzed by the titanium-BINOLate species generated in situ from a mixture of enantiopure BINOL (1,1'-bi-2-naphthol), Ti(OiPr)4, and H2O in the presence of benzylamine in toluene, was investigated in detail using a combination of reaction profile measurements, nonlinear effect (NLE) studies, solution (1)H NMR analysis, electrospray ionization mass spectrometry (ESI-MS), as well as the results obtained from screening of dynamic catalyst library of complexes L(a)/Ti/L(b) (L(a) or L(b) = chiral diol ligands). The BINOL-to-titanium ratio and the presence or absence of water in the catalytic system were found to exert profound influences on both reactivity and enantioselectivity of the reaction. The NLE studies revealed that the titanium species involved in the catalysis should contain more than one BINOL unit, either within or at the periphery of the catalytic cycle. ESI-MS analysis of the catalytic systems provided strong support in favor of the mechanistic proposal that titanium complexes bearing the Ti(BINOLate)2 moiety should be the active species responsible for the catalysis, which was further confirmed by the observation of synergistic effect of the heteroligand combinations during screening of the dynamic catalyst library. ESI-MS analysis of the reaction system indicated that water does not take part in the catalyst generation, which is an unprecedented finding in contrast to the previous mechanistic understandings in the titanium catalytic chemistry involving the participation of water. Most probably, water functions as a proton shuttle in the catalysis, facilitating the proton transfer between the reactants. Furthermore, the origin of (+)-NLE observed in the present catalytic system is rationalized on the basis of the ESI-MS analysis of the catalyst system prepared from a 1:1 pseudoracemic mixture of (S)-BINOL and (R)-3,3',6,6'-D4-BINOL. Finally, the reactivity differences between several couples of epoxide/amine combinations were tentatively rationalized on the basis of the arguments on their relative coordination preferences, and several other aliphatic amines were also found to efficiently ring-open the titled epoxide in excellent enantioselectivities. The results from this study are expected to shed some light on the often elusive chemistry of Ti(IV)-based catalytic systems where water or molecular sieves (or alcohols, etc.) are found to play an important yet inexplicable role and may help the search for effective asymmetric Ti(IV) catalysts for other types of reactions.

中文翻译：

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钛/BINOLate/水体系催化4,4-二甲基-3,5,8-三氧杂双环[5.1.0]辛烷不对称开环氨解的机理：含Ti(BINOLate)2的证据活性催化剂实体和水的作用

4,4-二甲基-3,5,8-三氧杂双环[5.1.0]辛烷与苄胺的对映选择性开环氨解机制，由对映纯的BINOL混合物原位生成的钛-BINOLate物种催化（1 ,1'-bi-2-naphthol)、Ti(OiPr)4 和 H2O 在甲苯中存在苄胺的情况下，使用反应曲线测量、非线性效应 (NLE) 研究和溶液 (1) 的组合进行详细研究H NMR 分析、电喷雾电离质谱 (ESI-MS) 以及从配合物 L(a)/Ti/L(b) 的动态催化剂库筛选获得的结果（L(a) 或 L(b) =手性二醇配体）。发现 BINOL 与钛的比例以及催化体系中水的存在与否对反应的反应性和对映选择性都有深远的影响。NLE 研究表明，参与催化的钛物种应该包含一个以上的 BINOL 单元，无论是在催化循环内还是在催化循环的外围。催化系统的 ESI-MS 分析提供了强有力的支持，支持带有 Ti(BINOLate)2 部分的钛配合物应该是负责催化的活性物质的机制建议，这通过观察到的协同效应进一步证实在筛选动态催化剂库期间的杂配体组合。反应体系的 ESI-MS 分析表明，水不参与催化剂的生成，这与之前钛催化化学中涉及水参与的机理理解相比，这是一个前所未有的发现。最可能，水在催化中起质子穿梭的作用，促进反应物之间的质子转移。此外，根据对由 (S)-BINOL 和 (R)- 的 1:1 假外消旋混合物制备的催化剂系统的 ESI-MS 分析，在本催化系统中观察到的 (+)-NLE 的起源合理化。 3,3',6,6'-D4-BINOL。最后，几对环氧化物/胺组合之间的反应性差异根据它们的相对配位偏好的论点暂时合理化，并且还发现其他几种脂肪胺以优异的对映选择性有效地开环标题环氧化物。预计这项研究的结果将揭示通常难以捉摸的基于 Ti(IV) 的催化系统的化学性质，其中水或分子筛（或醇等）。