Multiple N−H Bond Activation: Synthesis and Reactivity of Functionalized Primary Amido Ytterbium Complexes

A series of new functionalized amido complexes of ytterbium, [Cp2YbNHR]2 (R = 8-quinolyl(Qu)
(1a), 2-pyridyl(Py) (1b), 2-aminophenyl (1c), 3-amino-2-pyridyl (1d), and Cp2Yb[NHC6H4(CH2NH2-2)]
(1e), have been synthesized by metathesis of Cp2YbCl and the corresponding amido lithium salts. Their
reactivity toward carbodiimides has been investigated, in which multiple N−H activation behavior for
metal-bound neutral NH2 and anionic nitrogen-containing fragments, a property that is expressed without
dissociation from the lanthanide center, is observed. These results provide an alternative mechanistic
insight for the metal-mediated mono- and diguanylation of primary amines and elucidate factors that
affect the chemo- and regioselectivities of the addition and protonation steps. Reaction of 1a with 2
equiv of RNCNR [R = cyclohexyl (Cy), isopropyl (iPr)] leads to the formal insertion of carbodiimide
into the N−H bond of the Yb-bonded amido group to yield Cp2Yb[η1:η2-RNC(NHR)NQu]2 [R = Cy
(2a), iPr (2b)]. Interestingly, treatment of 1b with RNCNR affords the unexpected products (Cp2Yb)2[μ-η2:η2-PyNC(NR)2](THF) [R = Cy (3a), iPr (3b)], representing the first example of dianionic
guanidinate lanthanide complexes. The reaction of 1c with 2 equiv of RNCNR in THF at room
temperature leads to the isolation of the single N−H addition products Cp2Yb[η1:η2-RNC(NHR)NC6H4NH2-2] [R = Cy (4a), iPr (4b)] in satisfied yields, while treatment of 1c with 4 equiv of RNCNR
under the same conditions gives the double N−H addition products Cp2Yb[η1:η2-RNC(NHR)NC6H4{NC(NHR)2-2}] [R = Cy (5a), iPr (5b)], via the intraligand proton transfer from chelating NH2 to the
guanidinate group of 4 to give new amido intermediates, followed by a second RNCNR insertion
into the N−H bond of the resulting amido groups. Complexes 5 can also be obtained by reacting 4 with
1 equiv of RNCNR. The double-addition product Cp2Yb[η1:η2-CyNC(NHCy)NC5H3N{NC(NHCy)2-3}] (6) could be obtained as red crystals from the 1:4 reaction between 1d and CyNCNCy in 63%
yield. Interestingly, 6 can be converted into (Cp2Yb)2[η2:η3-(CyN)2CNC5H3N{NC(NHCy)2-3}] (7) under
reflux in THF and with liberation of a neutral diguanidine, C5H3N(NC(NHCy)2)-2,3. A preference of the
proton transfer to the second carbodiimide insertion into the N−H bond in the formation of 5 and 6 has
been confirmed by the fact that treatment of weaker acidic 1e with an excess of carbodiimides in THF/toluene, even with prolonged heating, provides only the monoaddition product Cp2Yb[η2:η1-CyNC(NHCy)NC6H4(CH2NH2-2)] [R = Cy (8a), iPr (8b)]. All complexes were characterized by elemental analysis
and spectroscopic properties. The structures of all complexes except 2b, 3b, 4a, and 5b were also
determined through X-ray crystal diffraction analysis.

一系列新型官能化的二(环戊二烯基(cyclopentadienyl, Cp))镱酰胺配合物[Cp₂YbNHR]₂（其中R分别为8-喹啉基(8-quinolyl, Qu)（1a）、2-吡啶基(2-pyridyl, Py)（1b）、2-氨基苯基（1c）、3-氨基-2-吡啶基（1d）以及Cp₂Yb[NHC₆H₄(CH₂NH₂-2)]（1e）），通过二(环戊二烯基)氯化镱(Cp₂YbCl)与相应酰胺锂盐的复分解反应合成得到。本研究考察了该系列配合物与碳二亚胺(carbodiimides)的反应活性，观察到与金属键合的中性NH₂及含氮阴离子片段存在多重N-H活化(N-H activation)行为，该过程无需从镧系中心(lanthanide center)解离即可进行。上述结果为金属介导的伯胺单胍基化(guanidylation)与双胍基化反应提供了新的机理性认知，并阐明了影响加成与质子化步骤化学选择性(chemo-selectivity)及区域选择性(regioselectivity)的关键因素。

1a与2当量的RN=C=NR[R为环己基(cyclohexyl, Cy)、异丙基(isopropyl, iPr)]反应时，碳二亚胺可形式上插入Yb键合的酰胺基团的N-H键中，生成Cp₂Yb[η¹:η²-RNC(NHR)NQu]₂[R=Cy(2a)、iPr(2b)]。值得注意的是，1b与RN=C=NR反应则得到意料之外的产物(Cp₂Yb)₂[μ-η²:η²-PyNC(NR)₂](四氢呋喃(tetrahydrofuran, THF))[R=Cy(3a)、iPr(3b)]，这是首例双阴离子胍基(dianionic guanidinate)配位的镧系配合物。

1c与2当量的RN=C=NR在四氢呋喃(THF)中室温下反应，可分离得到单N-H加成产物Cp₂Yb[η¹:η²-RNC(NHR)NC₆H₄NH₂-2][R=Cy(4a)、iPr(4b)]，产率可观；当1c与4当量的RN=C=NR在相同条件下反应时，则得到双N-H加成产物Cp₂Yb[η¹:η²-RNC(NHR)NC₆H₄{NC(NHR)₂-2}][R=Cy(5a)、iPr(5b)]。该反应路径为：配体内质子转移(intraligand proton transfer)，将螯合的NH₂的质子转移至中间体4的胍基基团，生成新型酰胺中间体，随后第二分子RN=C=NR插入该中间体酰胺基团的N-H键中。配合物5也可通过4与1当量的RN=C=NR反应得到。

1d与CyN=C=NCy以1:4的摩尔比反应，以63%的产率得到红色晶体状的双加成产物Cp₂Yb[η¹:η²-CyNC(NHCy)NC₅H₃N{NC(NHCy)₂-3}]（6）。有趣的是，6在THF中回流(reflux)条件下可转化为(Cp₂Yb)₂[η²:η³-(CyN)₂CNC₅H₃N{NC(NHCy)₂-3}]（7），同时释放出中性双胍C₅H₃N(NC(NHCy)₂)-2,3。

在生成5和6的过程中，质子转移优先于第二分子碳二亚胺对N-H键的插入反应，这一点可通过以下实验得到验证：将酸性较弱的1e与过量碳二亚胺在THF/甲苯混合溶剂中反应，即便延长加热时间，也仅能得到单加成产物Cp₂Yb[η²:η¹-RNC(NHR)NC₆H₄(CH₂NH₂-2)][R=Cy(8a)、iPr(8b)]。

所有配合物均通过元素分析(elemental analysis)与波谱学性质(spectroscopic properties)进行了表征，除2b、3b、4a及5b外，其余配合物的结构均通过X射线单晶衍射分析(X-ray crystal diffraction analysis)得以确定。