Manganese- or iron-catalyzed homocoupling of grignard reagents using atmospheric oxygen as an oxidant.

Homocoupling reactions of aryl, alkenyl, and alkynyl Grignard reagents are an easy and efficient access to symmetrical dior polyaromatic, olefinic, or acetylenic conjugated compounds. The potential applications of such compounds in optical materials, molecular devices, and organic conductors are well-recognized.1 Therefore, for large-scale applications, it is interesting to develop more convenient methods with respect to environmental and economic considerations. Recently, we2 and others3 have demonstrated the efficiency of the iron-catalyzed homocoupling of aryl Grignard reagents using 1,2-dihalogenoethanes as an oxidant. Following that, Knochel4 described an elegant transition-metal-free homocoupling reaction of organomagnesium compounds by direct oxidation with 3,3′,5,5′-tetra-tert-butyl-4,4′-diphenoquinone. However, for industrial applications, these methods are limited since they require a stoichiometric amount of organic oxidant. In fact, the choice of the oxidant is crucial for any effective preparative method, and atmospheric oxygen is obviously the best candidate. Now, we would like to report our progress in this field. A preliminary experiment showed that excellent yield of 4,4′dimethoxydiphenyl 1 is obtained by bubbling dry air into a solution of 4-anisylmagnesium bromide in the presence of FeCl3 (Scheme 1). The efficiency of the iron catalysis should be underlined since, in the absence of iron salts, Grignard reagents generally react very quickly with oxygen to give various products (mainly ROH and RH) but only traces of homocoupling product.5 This promising result encouraged us to extend the scope of the reaction to various aryl Grignard reagents (Table 1). Thus, simple and functionalized biaryl compounds were synthesized in good yields (entries 1-5). It is noteworthy that the use of pure oxygen instead of atmospheric oxygen has no significant influence on the yields (entries 1 and 2). The conditions described above also allow the coupling of alkenyl Grignard reagents (entries 6 and 7). The corresponding conjugated dienes were obtained in moderated yields, and the reaction is stereoselective (entry 7). Unfortunately, with alkynylmagnesium halides, the reaction gave an untractable mixture of heavy products.5 During our investigations on ironand manganese-catalyzed cross-coupling reactions of Grignard reagents, we often noticed similar behavior between the two metals. As a consequence, we tried to perform the homocoupling of Grignard reagents under manganese catalysis. As shown in Table 2, excellent yields of homocoupling products were obtained by using 5 mol % of MnCl2. Various aryl and heteroaryl Grignard reagents have been used successfully (entries 1-10). The reaction is chemoselective; thus, ester, nitrile, or nitro groups are tolerated (entries 4-6 and 9). Under the same conditions, â-monoand â,â-bisubstituted alkenyl Grignard reagents afforded the corresponding conjugated dienes in good yields. It should be noted that the coupling is highly stereoselective (entries 12 and 13). These results are interesting since MnCl2, as FeCl3, is a very suitable catalyst from both the economic and environmental point of view. As a rule, the manganese-catalyzed reaction gave better yields than the iron-catalyzed reaction, especially for the preparation of conjugated dienes. These excellent results prompted us to try to couple hexynylmagnesium chloride again by using MnCl2 in place of FeCl3 as catalyst. We were very pleased to obtain 5,7-dodecadiyne 14 in 91% yield (entry 14). The reaction was successfully extended to various alkynyl Grignard reagents (entries 14-17). This should be emphasized since diynes are very important in materials sciences1 and for the elaboration of natural products.6 In order to illustrate the synthetic potential of this coupling reaction in total synthesis, we decided to prepare the N-methylcrinasiadine 20 (Scheme 2), a natural product extracted from Lapiedra martinezzi (Amaryllidaceae). The 2,2′-diiodo-N-methyl-4,5-methylenedioxybenzanilide 197 was treated with i-PrMgCl to give the corresponding di-Grignard reagent via an iodine-magnesium exchange (Scheme 2). The Scheme 1. Iron-Catalyzed Homocoupling of Anisylmagnesium Bromide with Atmospheric Oxygen as an Oxidant