Efficient Construction of Biaryls and Macrocyclic Cyclophanes via Electron-Transfer Oxidation of Lipshutz Cuprates

An efficient method for the homocoupling of aryl halides by electron-transfer oxidation of Lipshutz
cuprates (Ar2Cu(CN)Li2) with organic electron acceptors is disclosed. Thus, various types of Lipshutz
cuprates are prepared by successive treatment of aryl or heteroaryl bromides with tert-butyllithium and
CuCN. The electron-transfer oxidation of Lipshutz cuprates with p-benzoquinones proceeds smoothly to
afford the corresponding homocoupling products in moderate to good yields. Furthermore, it can be
applied to the construction of either thiophene- or benzene-fused 10-membered ring cyclophanes. For
the synthesis of 10-membered cyclophanes, the linear C−Cu−C structure of Lipshutz cuprates should
be maintained in the dimetallacyclic intermediates, producing the large ring cyclophanes efficiently. The
X-ray analysis of the cyclophanes reveals that the difference in the bridging atoms results in the different
conformations of the macrocyclic rings. Thus, the silicon-bridged cyclophane 5a adopts a D2-symmetric
structure with a twisted rhombic arrangement of four thiophene rings, whereas the methylene- and oxygen-bridged cyclophanes 5b and 5c possess C2h- and C2-symmetric structures with chair- and boatlike
conformations, respectively. The 1H NMR spectrum of C2-symmetric 5c is temperature-dependent, and
the activation energy (ΔG⧧) for the conformational change is 10.1 kcal/mol.