Grignard reagents, cross-coupling reactions

Alkenes from vinyl iodides and Grignard reagents. Cross coupling of vinyl iodides with Grignard reagents to form alkenes is possible with catalysis by this palladium complex. Yields are 80-877o (six examples). Of more interest, the reaction occurs almost exclusively (>97%) with retention of configuration (equation I). 

Alkyl- and aryl-pyridazines can be prepared by cross-coupling reactions between chloropyridazines and Grignard reagents in the presence of nickel-phosphine complexes as catalysts. Dichloro[l,2-bis(diphenylphosphino)propane]nickel is used for alkylation and dichloro[l,2-bis(diphenylphosphino)ethane]nickel for arylation (78CPB2550). 3-Alkynyl-pyridazines and their A-oxides are prepared from 3-chloropyridazines and their A-oxides and alkynes using a Pd(PPh3)Cl2-Cu complex and triethylamine (78H(9)1397). 

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...

Although the formation of tetraalkylferrates, for example, in the first step of a cross-coupling reaction starting from Fe(-i-3)-salts and alkyl Grignard reagents, seems possible, until now there is no analytical or spectroscopic proof for such a species. In fact, it was shown that Fe(-i-3) is reduced by MeLi or MeMgBr to Fe(-i-2) under release of ethane [5, 6]. 

A tandem cyclisation/cross-coupling reaction between 6-halo-1-hexene 82 and Grignard reagents 83 is successfully catalysed by a NHC-Co catalytic system (Scheme 5.23) [23]. 

TABLE 3. Cross-coupling reaction of vinyl sulfones with Grignard reagents ... 

Aromatic and vinylic sulfides take part in cross-coupling reactions with Grignard reagents in the presence of Ni catalysts.336,337 This reaction has been applied to the enantioselective synthesis of binaphthyls using a standard chiral oxazoline ligand (Equation (25)) 338... 

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 early 1980s, one of the first preparations of substituted allenes was reported, which employed a palladium-catalyzed cross-coupling reaction of allenyl halides [9]. In this study, allenyl bromides 13 and various Grignard reagents 14 were coupled in the presence of catalytic amounts of a Pd(0) species, generated in situ by reduction of a Pd(II) salt. Trisubstituted allenes 15 were obtained with high regioselectivity (allene 15 alkyne 16 = 90 10 to 99 1) (Scheme 14.5). 

Finally, attention is drawn to the extensive work of Okazaki and co-workers, wherein two terphenyl units have been attached to a central functionality in order to create novel all-carbon molecular bowl-like molecules.97 For example, the novel molecular bowl compound Ar Br (Ar Br = 2,6-bis(CH2C6H3-2,6-Dmp2)-4-/fT/-butyl-l-bromophenyl), was synthesized by a cross-coupling reaction between the Grignard reagent of the iodoterphenyl... 

The Kumada cross-coupling reaction (also occasionally known as the Kharasch cross-coupling reaction) is a nickel- or palladium-catalyzed cross-coupling reaction of a Grignard reagent with an organic halide, triflate, etc. 

Chiral butenolides are valuable synthons towards y-butyrolactone natural products [37] and have also been successfully applied to the synthesis of paraconic acids. The lactone 91, readily available from the hydroxyamide (rac)-90 by enzymatic resolution [38] followed by iodolactonization, proved to be an especially versatile key intermediate. Copper(I)-catalyzed cross coupling reactions with Grignard reagents allowed the direct introduction of alkyl side chains, as depicted in 92a and 92b (Scheme 13) [39, 40]. Further... 

The enantioselective desymmetrization strategy can also be used for the palladium-catalyzed cross-coupling reactions with Grignard reagents. Thus, in the... 

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