Carbon-Carbon Coupling Catalysed By Organometallic Gold Complexes: 1,3-Dipolar Cycloadditions to Nitrones

The use of gold compounds in homogeneous catalysed organic reactions has been undervalued for many years due to the preconceived opinion that gold is an expensive and extremely chemically inert metal. However, recent reports have changed this assessment and gold salts in small amounts are known to display high catalytic activity.[1] Thus, it has been reported recently that anhydrous AuCl3 catalyses the formation of C-C and C-O bonds (usually mediated by hydrochloric and other protonic and Lewis acids).[2] Some examples include Michael type additions, selective cross cycloisomerisation/dimerisation of propargyl or allenyl ketones, benzannulation between o-alkynylbenzaldehides and alkynes or cyclisation of alkenyl furans. It is noteworthy that some of these reactions[2a] can be also catalysed by silver salts but with much lower yields. The 1,3-dipolar cycloaddition of nitrones to alkenes is a powerful synthetic method that has found numerous applications in the synthesis of a variety of carbon frameworks.[3] Several laboratories have focused on the development of Lewis acidic reagents to modulate the selectivity of the reaction.[4] Despite the extensive study performed, there are not many examples in which a metallic complex catalyses the dipolar cycloaddition. Most of these reactions require the presence of a metallic complex and nitrone in a 1:1 molar ratio. Recently, we have carried out stoichiometric reactions of the N-benzil-C(2-pyridil)nitrone, 1, with different dipolarophiles in the presence of zinc and silver compounds.[5] Apart from an increase of the reaction rate and the selective formation of one of the possible isomers, we have shown the formation of zinc and silver-nitrone complexes during the reaction, which behave as the intermediates in the cycloaddition process. As suggested by the results obtained with silver complexes, we decided to test gold derivatives (in the oxidation states of I and III). Interestingly, we have found that they can be used not only as stoichiometric reagents but they can also mediate these cycloadditions in catalytic amounts (5 to 10 mol % respect to the nitrone). Here we present the results on the 1,3-dipolar cycloaddition reaction of the N-benzil-C(2-pyridil)nitrone (2-PyBN), 1, and methylacrilate, 2, (Eq. 1) catalysed by gold(III) derivatives.