Cu-Catalyzed Fe-Driven C sp -C sp and C sp -C sp2 Cross-Coupling: An Access to 1,3-Diynes and 1,3-Enynes Sabir Ahammed, Debasish Kundu, and Brindaban C. Ranu* Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India * S Supporting Information ABSTRACT: An efficient C sp -C sp cross-coupling of alkynyl bromide and pinacol ester of alkynyl boronic acid catalyzed by CuFe 2 O 4 nanoparticles has been accomplished in dimethyl carbonate to produce unsymmetric 1,3-diynes. This protocol is also extended for the C sp -C sp2 coupling of alkynyl bromide and alkenyl boronic acid to provide conjugated 1,3-enynes. The aliphatic, aromatic, and heteroaromatic alkynes couple with various substituted alkynyl/alkenyl boronates/boronic acids by this procedure to furnish a library of 1,3-diynes and enynes in high yields. The catalyst was easily separated by an external magnet and recycled 10 times. ■ INTRODUCTION The unsymmetric 1,3-diynes have received considerable attention as these units are important structural motifs in many natural products 1 and molecules of pharmaceutical and material interest. 2 For example, norcapillene, 3 thiarubrine, 4 and falcarindol 5 containing this subunit showed prominent bio- logical activities. Thus, the construction of an unsymmetric 1,3- diyne moiety is of much interest. Although there are many methods for the synthesis of symmetric diynes, 6 those unsymmetric ones still remain a challenge. Cadiot-Chodkiewicz cross-coupling of haloalkyne and terminal alkyne catalyzed by Cu(I) is the most widely used method for the synthesis of unsymmetric diynes. 7 However, this protocol is often associated with low efficiency and poor selectivity. During the past few years, a few other methods involving Pd-catalyzed cross-coupling of 1,3-diynylzincs, 8a C sp -C sp cross-coupling of alkynyl bromides and terminal alkynes, 8b nickel-catalyzed cross- coupling of acetylenic sulfones and alkynyl Grignard reagents, 9a NiCl 2 /Cu(I)-catalyzed oxidative coupling of two different alkynes, 9b Cu(I)-catalyzed coupling of alkynyl silanes, 10a cross-coupling of terminal alkynes with 1-bromoalkynes, 10b heterocoupling of terminal alkynes, 10c decarboxylative coupling of alkynyl carboxylates with 1,1-dibromoalkynes, 10d coupling of propiolic acid with terminal alkynes, 10e and coupling of terminal alkynes with cis-styrenyl bromides 10f were also reported. The conjugated 1,3-enynes are also of much importance as they are present in many biologically active naturally occurring and synthetic molecules 11 and are used as important building blocks in organic synthesis. 1 A straightforward approach for the synthesis of 1,3-enynes involves the Pd/Cu-catalyzed Sonoga- shira coupling of terminal alkyne with vinyl halide. 12 Several other methods based on noble-metal-catalyzed dimerization of terminal alkynes, 13a coupling of an alkyne and a structurally defined organometallic alkene, 13b and Suzuki coupling of chloroenynes with boronic acid 13c were also developed. In view of the importance of unsymmetric 1,3-diynes and conjugated 1,3-enynes, there is a need for a more efficient and general procedure for the synthesis of both molecules involving less expensive metals and reagents. The CuFe 2 O 4 nanoparticle is a well-known catalyst for carbon-heteroatom bond formation 14 (C-N, C-O, C-S, C-Se, C-Te), although it is less explored for C-C bond formation. It is also commercially available. Thus, we became interested to find its activity toward C-C bond formation, particularly C sp -C sp coupling, and we report here a novel common protocol for C sp -C sp and C sp - C sp2 coupling of alkynyl bromides with pinacol ester of alkynyl boronic acid/alkenyl boronic acid using a magnetically separable CuFe 2 O 4 nanoparticle catalyst in a green reaction medium, dimethyl carbonate in the presence of a base (Scheme 1), as a part of our continuing efforts to explore nanoparticles for useful reactions. Received: May 20, 2014 Published: July 21, 2014 Scheme 1. Synthesis of Conjugated Diynes and Enynes Article pubs.acs.org/joc © 2014 American Chemical Society 7391 dx.doi.org/10.1021/jo5011069 | J. Org. Chem. 2014, 79, 7391-7398