Aryl Grignards

Formation of aryl Grignard reagents (Section 14 4) Aryl halides react with magnesium to form the corresponding arylmagnesium halide Aryl iodides are the most reac tive aryl fluorides the least A similar reaction occurs with lithium to give aryllithium reagents (Section 14 3)... 

Anthocyanidins were first synthesi2ed by reaction of an aryl Grignard reagent with a coumarin (93). 

For the synthesis of a suitable arylboron compound, usually an aryl halide is converted to an aryllithium or aryl Grignard derivative, and then reacted with a trialkoxyborane to yield an arylboronic ester, e.g. the phenylboronic acid diisopropyl ester 13 from bromobenzene 11 ... 

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

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). 

Organometallic compounds can be hydrolyzed by acid treatment. For active metals such as Mg, Li, and so on, water is sufficiently acidic. The most important example of this reaction is hydrolysis of Grignard reagents, but M may be many other metals or metalloids. Examples are SiRs, HgR, Na, and B(OH)2- Since aryl Grignard and aryllithium compounds are fairly easy to prepare, they are often used to prepare salts of weak acids, for example,... 

Organomercury compounds undergo a similar reaction. Alkyl and aryl Grignard reagents can be converted to carboxylic esters with Fe(CO)5 instead of CO. Amides have been prepared by the treatment of trialkyl or triarylboranes with CO and an imine, in the presence of catalytic amounts of cobalt carbonyl ... 

Cross-Coupling of Arylchloridcs with Aryl Grignard Reagents... 

CROSS-COUPLING OF ARYLCHLORIDES WITH ARYL GRIGNARD REAGENTS (KUMADA REACTION)... 

The conversion of diarylthallium trifluoroacetates to aromatic iodides by treatment with molecular iodine is thus analogous to the well-known conversion of diarylmercury derivatives with iodine to a mixture of an aromatic iodide and an arylmercury iodide (134), but it is much more effective as a synthetic tool because of the spontaneous disproportionation to product of the intermediate arylthallium trifluoroacetate iodide. The present procedure thus provides a practical synthetic method for the ultimate conversion of aryl Grignard reagents to aromatic iodides. 

This phenol synthesis complements the analogous reaction (see below) from arylthallium ditrifluoroacetates (147). Although yields are only moderate, the procedure represents a viable conversion of aryl Grignard reagents to phenols. It is a practical method, however, only when the diarylthallium trifluoroacetate precursor is formed via the Grignard route the alternative synthesis via symmetrization of arylthallium ditrifluoroacetates is obviously circuitous, since the latter compounds may be converted directly to phenols. 

More typical examples are the amino ethers (3) used as anti-histamine or anti-Parkinson drugs according to the substituents. These are obviously derived from the alcohols (4) which are made from an aryl Grignard reagent and a benzaldehyde. Either starting material may bear the substituent X the choice can be made according to availability and so that side reactions are avoided,... 

Example Sometimes copper solves other regioselecL-ivity problems. Addition of aryl Grignard (28) to enone (29) gives the anomalous product (30) in which the electrophile (29) has been attacked at the right atom but the nucleophile (23, arrows) has attacked with the wrong atom. 

With alkyl-, allyl-, benzyl-, or aryl-Grignard or lithium reagents 72 0,N-acetals 473 give the N,N-bis-silylated primary amines 474 in high yields these are converted by methanol into the free primary amines 44 and MeOSiMc3 13a [60] (Scheme 5.22). 

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

Yasuda S, Yorimitsu H, Oshima K (2008) Synthesis of aryliron complexes by palladium-catalyzed transmetalation between [CpFe(CO)2l] and aryl Grignard reagents and their chemistry directed toward organic synthesis. Organometallics 27 4025 027 Jonas K, Schieferstein L (1979) Simple route to Li- or Zn-metalated r -cyclopentadien-yliron-olefin complexes. Angew Chem Int Ed Engl 18 549-550... 

Nolan and colleagues published in 1999 the first coupling between aryl chlorides, bromides or iodides and aryl Grignards, in which an in situ generated NHC-Pd complex served as catalyst. The reaction proceeded in most cases in excellent yields, however, very sterically hindered products formally derived from aryl halides and aryl Grignards both possessing orf/io-substituents could not be obtained [75] (Scheme 6.16). 

Scheme 6.16 Nolan conditions for the coupling between aryl halides and aryl Grignards...

The corresponding bromides and iodides show concentration-dependent behavior and in very dilute solutions they exist as monomers. In tetrahydrofuran, there is less tendency to aggregate, and several alkyl and aryl Grignard reagents have been found to be monomeric in this solvent. 

Conventional aryl Grignard procedures have been used in the... 

The order of reactivity of halides with magnesium is RI > RBr > RC1 (very few organomagnesium fluorides have been prepared), i) Aryl Grignard reagents are more easily prepared from aryl bromides and aryl iodides than from aryl chlorides, which react very sluggishly. 

RM = Alkyl or Aryl Grignards, Alkyl or Aryl Lithium, R2NNa, RONa... 

---