Structural and reactivity insights in Mg–Zn hybrid chemistry: Zn–I exchange and Pd-catalysed cross-coupling applications of aromatic substrates

• Published in: Chemical science (Cambridge) 2014, Vol.5 (9), p.3552-3562
• Main Authors: Bluemke, Tobias D., Clegg, William, García-Alvarez, Pablo, Kennedy, Alan R., Koszinowski, Konrad, McCall, Matthew D., Russo, Luca, Hevia, Eva
• Format: Article
• Language: English
• Subjects: Activation; Exchange; Ion exchangers; Magnesium; Metalorganic compounds; Palladium; Sheds; Zinc
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/C4SC01263A

Expanding the synthetic potential of Mg-Zn hybrid organyl reagents (generated via transmetallation reactions), this study uncovers a versatile approach, involving a sequence of direct Zn-I exchange and Pd catalysed cross-coupling reactions which grants access to a wide range of asymmetric bis(aryls). By combining X-ray crystallography with ESI-MS and non-deuterium NMR spectroscopic studies, new light is shed on the heterobimetallic constitution of the intriguing organometallic species [(THF) sub(4)MgCl sub(2)Zn(tBu)Cl] (1) and [{Mg sub(2)Cl sub(3)(THF) sub(6)} super(+){ZntBu sub(3)} super(-)] (2), formed through transmetallation of tBuMgCl with n equivalent amounts of ZnCl sub(2) (n= 1 and 3 respectively). Operating by cooperative effects, alkyl-rich hybrid 2 can effectively promote direct Zn-I exchange reactions with aromatic halides in short periods of time at room temperature in THF solution. The structural elucidation of key organometallic intermediates involved in some of these Zn-I exchanges, provides new reactivity insights into how these bimetallic systems operate. Thus, while the reaction of 2 with 3 equivalents of 2-iodoanisole (3b) gives magnesium dizincate [{Mg(THF) sub(6)} super(2+){Zn( o-C sub(6)H sub(4)-OMe) sub(3)} sub(2) super( -)] (4) which demonstrates the 3-fold activation of the tBu groups attached to Zn in 2, using 2-iodobenzonitrile (3i), only two tBu groups react with the substrate, affording [(THF) sub(4)MgCl(NC-o-C sub(6)H sub(4))ZnI(o-C sub(6)H sub(4)-CN)(TH F)] (7). In 7 Mg and Zn are connected by an aryl bridge, suggesting that the formation of contacted ion-pair hybrids may have a deactivating effect on the outcome of the Zn-I exchange process. A wide range of homoleptic tris(aryl) zincate intermediates have been prepared in situ and used as precursors in Pd catalysed cross-coupling reactions, affording bis(aryls) 6a-s in excellent yields under mild reaction conditions without the need of any additive or polar cosolvent such as NMP or DMI.