Grignard reagents-Iron chloride

Ferric chloride-Silica, 134 Ferric nitrate/KlO Bentonite, 134 Grignard reagents-Iron(III) reagents, 211... 

An early report by Oddo suggested that a product containing two heterocyclic residues and one iron atom per molecule was obtained by the action of ferric chloride on the 2-methylindole Grignard reagent. - ... 

TABLE IRON CATALYZED CROSS COUPLING REACTIONS OF GRIGNARD REAGENTS WITH (HETEROJARYL CHLORIDES OR -TRIFLATES... 

Iron-catalyzed cross-coupling reactions of various acyl chlorides or thioesters with Grignard reagents have been pioneered by Marchese et al. and other research groups.322 These transformations provide general and convenient access to a wide range of ketones and have been further extended to the use of a supported iron(lll) complex.323... 

Recent notable improvements by Knochel and co-workers include iron-catalyzed cross-coupling reactions of various acid chlorides 148 with dialkylzinc reagents (Equation (24))324 as well as the iron-catalyzed arylation of aroyl cyanides 149 with Grignard reagents (Equation (25)).3 5 In the first case Knochel s reaction conditions tolerate ester groups on the organozinc compounds, while in the latter case ester, aryl alkyl ether, cyano, and chloro functionalities on the aromatic moieties are compatibles with the reaction conditions. 

Another convenient method of preparing this Jt-complex of iron is a two-step process in which the first step involves preparation of cyclopentadienyl Grignard reagent, such as 2,4-cyclopentadienylmagnesium bromide CsHsMgBr which may then be combined with ferric chloride to yield dicyclopen tadienyl iron ... 

However, arylmagnesium organometaUics can only be used in a few cases " like an iron-catalyzed homocoupling (equation 92) . Iron catalysis is further used for the dechlorination of electron-rich aryl chlorides by Grignard reagents . ... 

The first iron-catalyzed acylation of Grignard reagents was described by Kharasch and coworkers in 1944 (Scheme 6). They reported only one example of reaction between methyknagnesium iodide and mesitoyl chloride in the presence of iron(III) chloride in diethyl ether. 

Twenty-five years later, a dramatic improvement was reported by Fiandanese, Marchese and coworkers ° . They discovered that excellent yields of ketone were obtained when diethyl ether is replaced by THF. Moreover, iron acetylacetonate is used as a catalyst instead of iron(III) chloride because it is not hygroscopic and easier to handle. The scope of the procedure is very large and the reaction occurs highly chemoselectively under mild conditions (0 °C). It should be noted that excellent yields are obtained from stoichiometric amounts of Grignard reagents (Table 3). 

In 1971, Tamura and Kochi described the reaction of aUcyl Grignard reagents with alkenyl bromides in the presence of iron(III) chloride in THF. Only very reactive snbstrates such as vinyl and propenyl bromide were nsed (Scheme 16). Yields of conpling product are moderate to good but, unfortunately, a large excess of alkenyl bromide is required (3 to 9 equivalents). ( )-Bromopropene reacts 15 times faster than the (Z)-isomer. It should be noted that the reaction is stereoselective. 

In 2002, Figad re and coworkers reported the mono-reduction of 2-aryl (or heteroaryl)-1,1-dibromo-l-alkenes (Scheme 23). The reaction is achieved with one equivalent of isopropylmagnesium chloride in the presence of iron(III) acetylacetonate. Pure ( )-alkenyl bromides are obtained. With two equivalents of alkyl Grignard reagent, the mono-substituted product is obtained in moderate yield. 

The reaction can be performed in diethyl ether in the presence of iron(III) acetylaceto-nate, as reported by Nagano and Hayashi in 2004, or in the presence of FeCl(salen) or iron(III) chloride/triethylamine, as described by Bedford and coworkers (Scheme 39). The latter compared several ligands (amines , phosphines ) and the best results were obtained with triethylamine, TMEDA or DABCO. In all cases, the reactions have to be performed in refluxing diethyl ether and the Grignard reagent has to be added at once Unfortunately, these reaction conditions are only useable on a very small scale (1 mmol) but they cannot be used for large-scale applications. 

In 2005, Cahiez and coworkers and Nagano and Hayashi showed that a catalytic amount of iron(III) chloride is efficient when a suitable oxidant is added to the reaction mixture (Figure 3). Nagano and Hayashi used an excess of 1,2-dichloroethane (the stoichiometric amount is 0.5 equivalent) in refluxing diethyl ether to couple various aryl Grignard reagents in high yield (Scheme 46). 

In 1976, Pasto and coworkers described the Sn2 reaction of primary and secondary alkyl Grignard reagents with terminal and non-terminal propargyhc chlorides (Scheme 48). Only 0.1% iron(III) chloride is necessary to obtain various allenes in good yields. 

In 1998, Oshima and coworkers ° reported few examples of radical cyclization mediated by Grignard reagents in the presence of iron(II) chloride (Scheme 57). However, this reaction often gives moderate yields. 

Chromone-2-carbonyl chloride (496) reacts readily with a Grignard reagent to yield a ketone (497) without the need to add iron (III) chloride or to maintain the temperature at -70 °C (81JCS(P1)2552> as is customary in order to suppress the formation of f-alcohol. 

The application of transition metal catalysis provided new opportunities to introduce diverse functionality to the diazepine ring system. Iron-catalyzed cross-coupling of Grignard reagents with the imidoyl chloride 40 provided a convenient and efficient method for substituting the heterocyclic ring (Scheme 9) <20060L1771>. 

Ketone synthesis. This iron complex is an efficient catalyst for the reaction of a wide variety of Grignard reagents with aromatic or aliphatic acyl chlorides to form ketones in 70-90% yield. 

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