Arylation Grignard compounds

Whereas aryl Grignard compounds afford good yields of sulfones with sulfonyl fluorides298 299, phenyllithium is mainly chlorinated by a-toluene-sulfonyl chloride on the other hand, the corresponding fluoride yields only a trace of the expected mono-sulfonylation product, while the main product is 26 obtained by twofold sulfonylation300 (equation 61). 

High yields of -substituted allenic primary amines 227 are obtained by the CuBr-Me2S-or NiCh Ph2PCH2CH2CH2PPh2-catalysed reaction of the acetylene derivative 226 with aryl Grignard compounds and subsequent deprotection by flash chromatography219. 

Chiral sulfinimines 236 are very useful intermediates for the preparation of enantiomer-ically pure primary amines 237 (equation 158) . This reaction has been applied to the synthesis of a-amino acids . For sulfinimines obtained from simple ketones, lithium reagents are preferable for the addition , while for cyclic ketones organomagnesium compounds gave the best results. Addition of alkyl and aryl Grignard compounds to sulfinimines, derived from 3- and 4-substituted cyclohexanones, proceeds with excellent diastereoselectivity, depending on the stereochemistry of the ring substituents rather than the sulfinyl group . 

Functionalized aryl Grignard compounds, prepared by iodine-magnesium exchange according to the procedure reported by Cahiez, Knochel and coworkers in 1998, can be efficiently acylated. It is thus possible to prepare various polyfunctionalized diaryl ketones (Scheme 14). ... 

Fig. 5.47. Generation of functionalized aryl Grignard compounds through I/Hg exchange alkylation and hydroxy alkylation of the Grignard reagents to yield multiply substituted benzene derivatives.

Reaction of aryl Grignard compounds, obtained in situ by iodine-magnesium exchange, with C0CI2, presumably generates aryl radicals. In the presence of a double bond or aromatic ring an intramolecular radical cyclization may take place. This reaction was used for the synthesis of spiro-indolines.244 Oshima has applied cobalt-mediated tandem radical cyclization-cross-coupling reaction for the synthesis of benzyl-substituted heterocycles (Scheme 80).245... 

Because of the extraordinary strength of the carbon-fluorine bond, transition metal-mediated activation of fluoroalkanes and arenes is not easy to achieve. Nevertheless, activation of the C-F bond in highly electron-deficient compounds such as 2,4,6-trifluoropyrimidine, pentafluoropyridine, or hexafluorobenzene is possible with stoichiometric amounts of bis(triethylphosphano) nickel(O) [101] (Scheme 2.45). More recently Herrmann and coworkers [102] have described a variant of the Kumada-Corriu cross-coupling reaction [103] between fluorobenzene and aryl Grignard compounds which uses catalytic amounts of nickel carbene complexes. Hammett analysis of the relative kinetic rate constants indicated that the reaction proceeds via initial oxidative addition of the fluoroaromatic reactant to the nickel(O) species. 

Scheme 2.45 Transition metal-mediated activation of the aromatic carbon—fluorine bond and subsequent reactions. Ahoue stoichiometric reaction of electron-deflclent fluoroarenes with NI(0) complexes [101]. Belou Ni(0) carbene-catalyzed Kumada-Corriu coupling between fluoroarenes and aryl Grignard compounds [102].

The adducts of tri-O-acetyl-n-glucal with bromine or chlorine react with aryl Grignard compounds, to give products which, by analogy with those... 

Readily available nucleophilic aryl Grignard compounds can be coupled with aryl halide electrophiles to give unsymmetrical biaryls in the presence of Ni, Co, V, Ti, Cu, Cr, Fe, Pd and T1 salts [34] (Scheme 41). 

Nucleophilic ring-opening reactions are also observed. They occur, for instance, with secondary amines to give aminodienes 9 or with aryl Grignard compounds yielding aryl-1,3-dienes 10 ... 

As can be seen from the structures shown, A,jV-dimethyl-0-(methylsulfonyl)hydroxylainine (1) aminates alkyl Grignard compounds (to give 3) and aryl Grignard compounds (to give 4) with moderate yields. The same is true for benzylic anion type carbon atoms (5-9). Compounds (10) and (11) are formed from the corresponding malonates, while (12)-(16) are derived from (es-ter)enolates, although with aryl-stabilized anionic carbon atoms. Metalated cyanides lead to (17)-(19). 

The reaction between aryl Grignard compounds and 5-methoxy-6-nitroquinoline derivatives in THF has been found to proceed in a chemodivergent mode that depended on the functional groups present in the heterocyclic ring. Thus, the reactions that started from carbostyril derivatives afforded 6-(arylamino)carbostyrils as the major products, whereas those that started with 2-alkoxyquinolines gave exclusively 5-aryl-quinolines. 

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