SYNTHESIS aryl Grignard reagents

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. 

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. 

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... 

The reaction of magnesium metal with an alkyl or aryl halide in diethyl ether is the standard method for synthesis of Grignard reagents. The order of reactivity of the halides is RI > RBr > RC1. 

Preparation of the chiral biphenyls and binaphthyls with high enantiose-lectivity can be achieved via substitution of an aromatic methoxyl group with an aryl Grignard reagent using oxazoline as the chiral auxiliary.38 Schemes 8-10 and 8 11 outline the asymmetric synthesis of such chiral biaryl compounds. 

Grignard reaction, addition of methyl-magnesium bromide to thiophos-phoryl chloride, 46,102 addition of aryl Grignard reagents to diphenylchlorophosphine, 49, 66 Grignard reagents, synthesis and utility of unsolvated, 47, 116 titration of, 48, 48... 

Following these results with the salen complex, Bedford reported on the synthesis of a series of Fe(iii)-salen-type complexes and the use of one of them, 75 (Figure 14), for the coupling of aryl Grignard reagents with primary and secondary alkyl halides, in Et20 at 45 Fiirstner subsequently reported on the use of the tetrakis(ethylene)fer-... 

The successful synthesis of a cyclic oligoplumbane was not reported until 2003. The outcome of reactions of lead(II) halides with aryl Grignard reagents ArMgBr depends on both the steric requirements of the ligand and the reaction conditions. When Ar = 2- Bu-4,5,6-Me3C6H a monomeric plumbylene... 

Biphenyl synthesis. In the presence of l,4-dichloro-2-butene, aryl Grignard reagents couple to form biphenyls. The coupling involves electron transfer to the... 

Triazine may be used in the Gatterman aldehyde synthesis in place of hydrogen cyanide (Scheme 15) (67AG(E)940>. On treatment of 1,3,5-triazine with aryl Grignard reagents, the aryl aldehyde is formed (Scheme 16) (63MI22000). 

A simple single-step synthesis of symmetrical l,3-diar flbenzo[f]furans is achieved by the addition of 2equiv of an aryl Grignard reagent to 3-methoxyphthalide (Scheme 93) <2006SL2035>. 

It should be noted that direct substitution of sulfonate or iodide derivatives at C6 is sensitive to steric hindrance. Kishi reported a failure in the substitution of a primary tosylate by vinyl cuprate in the synthesis of mycalamides where C4 had two geminal methyl substituents. An alternate five step route was developed to introduce the vinyl substituent [119]. Direct substitution of a primary triflate by an aryl Grignard reagent is a key step in the formal synthesis of (+)-apicularen A from D-glucal [194]. Displacement of a triflate with an alkynyllithium has also been used in the total synthesis of (+)-panaxacol [195]. 

Polniaszek and Dillard [26] reported the stereospecific synthesis of S-(-l-)-cryptostyline. The key step is the stereoselective addition of the protected aryl Grignard reagent to the iminium salt (see Table 3, entry 2). The 2-substituted tetrahydraisoquinoline was obtained as the S-isomer in 100% optical purity. 

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