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Supplementary Information Supplementary figures, supplementary tables, supplementary methods and supplementary references.
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As a versatile metal, copper has demonstrated a wide application in acting as both organometallic reagent and catalyst. Organocuprates are among the most used organometallic reagents in the formation of new carbon–carbon bonds in organic synthesis. Therefore, revealing the real structures of organocuprates in solution is crucial to provide insights into the reactivity of organocuprates. Here we provide several important insights into organocuprate chemistry. The main finding contains the following aspects. The Cu(0) particles were detected via the reduction of CuX by nBuLi or PhLi. The Cu(II) precursors CuX2 (X=Cl, Br) could be used for the preparation of Gilman reagents. In addition, we provide direct evidence for the role and effect of LiX in organocuprate synthesis. Moreover, the EXAFS spectrum provides direct evidence for the exact structure of Li + CuX2 − ate complex in solution. This work not only sheds important light on the role of LiX in the formation of organocuprates but also reports two new routes for organocuprate synthesis.
Organocopper species are widely used in synthetic chemistry. Here the authors study the structure of the anionic complex formed from copper salts and lithium halides, showing it to be a key intermediate in the formation of organocuprates, and also show that Cu(II) precursors can form Gilman reagents.
Since the pioneering work of Gilman et al., 1 organocuprates have been widely employed as organometallic reagents in organic synthesis (including conjugate additions, the opening of epoxides and cross-coupling reactions) 2 ,3 ,4 ,5 ,6 ,7 . In the textbook, organocuprates are usually prepared through transmetalation of lithium, magnesium or zinc organometallics with Cu(I) salts 8 . Different coordination environments always drastically affect the reactivity or stabilities of organocuprates 9 . Up to now, a lot of synthetic methodologies involving organocuprate reagents have been developed, while great uncertainty still exists in the related mechanism 10 . Although several important crystal structures of organocuprates were reported 11 ,12 ,13 ,14 , it should be noted that solid-state structures often reflect the most thermodynamically stable species and are not necessarily the same as in solution state. Besides, organocuprates can exhibit complex behaviour in solution, often existing as a number of different species in equilibrium, thus further complicating their characterization. For that reason, the structure of organocopper compounds in solution cannot be inferred directly from crystal structures and must be determined independently.
The structures of organocuprate reagents in an ethereal solution have received wide attention, because they are strongly relevant to reactivity in real reaction conditions 15 ,16 ,17 . Nuclear magnetic resonance 18 ,19 ,20 and electrospray ionization–mass spectrometry 21 ,22 served as powerful tools and have been widely used in determining the structures of organocuprates in solution. The linear bonding geometry of the C–Cu–C moiety in cuprates such as MeCu(CN)Li, Me2CuLi and Me2-CuLi3LiX (X=I, CN) has been well established. In 1996, Knochel and colleagues 23 ,24 first introduced the extended X-ray absorption fine structure (EXAFS) to study the local structure of organocuprates from the reaction between CuCN and nBuLi. EXAFS spectroscopy provides a unique probe of the local structural environment of metal ions in non-crystalline systems 25 ,26 ,27 ,28 ,29 ,30 ,31 ,32 ,33 . The preliminary structure for lithium cyanocuprates based on EXAFS data has been elucidated. However, the role of cyanide and the difference between cyanide and other halide atoms still remain in debate 9 . Lipshutz et al. 21 and Koszinowski and colleagues 34 have pointed out the LiX could have a positive effect on the solubility of CuX (X=I, Br, Cl, CN) independently. The electrospray ionization–mass spectrometry was used to study the structure of formed ate complex 21 ,34 . However, determination of the exact structure, the role for LiX and application in organocuprates have still been not well-studied up to date. We started our research by investigating the effect of anion on organocuprates preparation. Here we show the anion effect of different Cu(I) precursors on Gilman reagent preparation. The EXAFS reveals that the LiX (X=Br, Cl) serves as the hidden link for organocuprates preparation from unfavoured CuX. A soluble cupric bromide anion intermediate is evidenced by EXAFS when adding LiBr to CuBr in tetrahydrofuran (THF). This CuX2 − Li + ate complex serves as a key intermediate in the generation of Gilman reagent ( Fig. 1 ). In addition, we also shed two other important findings in this work. First, the detection of copper nanoparticles produced after the addition of nBuLi or PhLi to CuX. Second, the Cu(II) precursors CuX2 (X=Cl, Br) can be used for the preparation of Gilman reagents.