Iron-catalyzed reactions Grignard reagents

Iron-Catalyzed Reactions of Grignard Reagents TABLE 1. Regioselective preparation of trimethylsilyl enol ether... 

VII. APPLICATIONS OF IRON-CATALYZED REACTIONS OF GRIGNARD REAGENTS IN ORGANIC SYNTHESIS... 

These last years, several syntheses of natural products using an iron-catalyzed reaction of Grignard reagents have been published. In 1969, Meinwald and Hendry used the reaction discovered by Kharasch and Tawney to prepare an allenic sesquiterpenoid isolated from the grasshopper Romalea Microptera (Scheme 61). 

E. Catalysis of Alkyl Disproportionation by Iron. Alkyl disproportionation is the sole reaction observed during the iron-catalyzed reaction of ethylmagnesium bromide and ethyl bromide.(47) The catalyst is a reduced iron species formed in situ by the reaction of iron(lI,III) with Grignard reagent, and ective... 

Cross coii ing of Grignard reagents with 1-alkenyl halides, in marked contrast to alkyl halides, occurs readily with the reduced iron catalyst, as described above. The iron-catalyzed reaction of Grignard reagents with 1-alkenyl halides can, however, be differentiated from the reaction with alkyl halides. Thus, a mixture of propenyl bromide and ethyl bromide on reaction with methylmagnesium bromide afforded butene-2 but no cross-over products such as pentene-2 or propylene. The latter certainly would have resulted if a propenyliron species per se were involved in the catalytic process. Cross coupling under tEese circumstances clearly merits further study. 

Scheme 4-242. Synthesis of ketones by iron-catalyzed reaction of acyl chlorides with Grignard reagents.

Iron-catalyzed reaction of imidoyl chlorides with Grignard reagents. 

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

Scheme 29 Iron-catalyzed cross coupling reaction of aryl Grignard reagents with alkyl halides...

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. 

In the course of a study on creation of a library of a great number of hetaryl ketones and related derivatives, Szewczyk et al. <2001AGE216> elaborated a ruthenium-catalyzed transformation of heterocycles with activated C-H bond by reaction with olefins and carbon monoxide. Thus, 253 gave 254, albeit in very poor yield. Synthetically, the more straightforward iron-catalyzed transformation was described by Fiirstner et al. <2002JA13856>. These authors reacted 255 with a Grignard reagent in the presence of Fe(acac)3 to afford the 7-alkyl-substituted derivative 256 in reasonable yield (acac = acetylacetonate). 

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