Palladium-catalyzed cross-coupling of aryl or vinyl iodides with ethyl diazoacetate.

Palladium catalyzed cross-coupling reaction has been developed into one of the most powerful methods for the formation of C-C bonds.1 Recently, remarkable progress has been made in the Pdcatalyzed cross-coupling reactions with carbon nucleophiles derived from active methylene compounds,1d ketones,2 esters,3 amides,4 and nitriles.5 Hydrazones have also been applied in this type of reactions as acyl anion nucleophiles.6 In connection with our interest in the chemistry of diazo compounds as nucleophiles,7 we have conceived that R-diazocarbonyl compounds, which are commonly used as carbene precursors,8 may be utilized as carbon nucleophiles in Pdcatalyzed coupling reactions. Diazo carbon bears a partial negative charge and thus has considerable nucleophilicity;9 however, to the best of our knowledge, diazo compounds have not been directly used as partners in Pd-catalyzed cross-coupling reactions.10 This may be attributed to the general belief that diazo decomposition should occur readily upon complexation with transition metals.8,11 Herein we report that ethyl diazoacetate (EDA) undergoes efficient Pd-catalyzed cross-coupling with aryl or vinyl iodides. Moreover, carbonylation occurs prior to the coupling if the reaction is carried out under an atmosphere of CO. An initial attempt to couple EDA with ethyl (Z)-3-iodopropenoate (1a) using Et3N as base and Pd(OAc)2 as catalyst in CH2Cl2 resulted in rapid diazo decomposition (Table 1, entry 1). Pd2(dba)3 also decomposed EDA (entry 2). To our delight, with PdCl2(PPh3)2 the reaction afforded cross-coupling product, albeit in low yield (entry 3). The yield could be slightly improved by Pd(PPh3)4 (entry 4). Other reaction parameters were then screened with this catalyst. Increasing the catalyst loading could further improve the yield (entry 5). The reaction seemed more favored in polar solvents such as MeCN, DMF, and acetone, but MeOH and DMSO resulted in diminished yields (entries 10, 11). Inorganic bases of Cs2CO3, K2CO3 were found unsuitable in this reaction (entries 12, 13). The introduction of 1 equiv of n-Bu4NBr as additive significantly improved the reaction (entry 15).12 However, Pd(0) catalyst containing more electron-rich phosphine ligands were found not effective in this reaction (entries 16, 17). Moreover, it was noteworthy that without Pd(0) catalyst no coupling product could be observed (entry 18). This experiment rules out the possibility of a conjugate addition-elimination mechanism for the formation of 2a.13 A series of vinyl iodides were then subjected to the optimized reaction conditions (Table 1, entry 15). The reaction gave crosscoupling products in moderate to good yields (Table 2). The strong electron-withdrawing substituent at the double bond was found necessary for this reaction since the reaction with â-iodo styrene gave no cross-coupling product. Besides, it was noted that the reaction proceeded with retention of configuration at the double bond. Next we conceived to extend the coupling reaction to aryl halides. However, when the above reaction conditions were applied to iodobenzene, the expected cross-coupling product was not obtained. After screening the reaction conditions, we found that by replacing Et3N with DBU, the above optimized conditions could be successfully applied to the coupling reaction with aryl iodides (Table 3). Table 1. Pd-Catalyzed Cross-Coupling of Iodide 1a with EDA