Metalation aryllithium

Helquist and coworkers60 have developed a six-membered ring annulation via a conjugate addition of aryllithium generated by metal-halogen exchange and subsequent intramolecular alkylation. This is illustrated in equation 71. 

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,... 

Molecular nitrogen (N2) reacts with aryllithium compounds in the presence of compounds of such transition metals as titanium, chromium, molybdenum, or vanadium (e.g., TiCl4) to give (after hydrolysis) primary aromatic amines. ... 

An example of intramolecular conjugate addition of aryllithium generated by halogen metal exchange reaction of 92 is illustrated in equation 79 . 

The aryl bromides undergo facile metalation with butyl lithium to produce aryllithium derivatives with the expected organometallic activity.9 For example, reaction of lithiated PPO with carbon dioxide produces a carboxylated PPO which exhibits unique blending characteristics18. 

An alternative synthesis of a thermally stable cyclopentadienyl functionalized polymer involved ring bromination of poly(oxy-2,6-diphenyl-l,4-phenylene), followed by lithiation with butyl lithium to produce an aryllithium polymer. Arylation of 2-norbornen-7-one with the metalated polymer yielded the corresponding 2-norbornen-7-ol derivative. Conversion of the 7-ol to 7-chloro followed by treatment with butyl lithium generated the benzyl anion which undergoes a retro Diels-Alder reaction with the evolution of ethylene to produce the desired aryl cyclopentadiene polymer, 6. 

The preparation of aryllithium reagents can also be performed by using t-butyllithium in a halogen-metal exchange, and aqueous potassium ferricyanide as an oxidant. 

From these studies of aryllithium complexes, it can further be concluded that the quadrupolar interaction is a very sensitive indicator of the type of aggregation and solvation state. In certain cases the /-value ranges overlap, but additional investigations can often easily clarify the ambiguity, such as the ligand/metal ratio. The latter can, for example, be determined by a solution H NMR spectrum of the solid material in a suitable solvent. 

TABLE 5. Aryllithiums Li—R lacking hetero-substituents by metal insertion into haloarenes, the reactions being generally conducted in diethyl ether and in the temperature range of 0°C to +40°C (refluxing ether)... 

TABLE 6. Aryllithiums Li—R carrying amino and alkoxy substituents prepared in diethyl ether by metal insertion into the corresponding bromoarene... 

TABLE 16. Heteroatom-free aryllithiums Li—R by halogen/metal permutation between bromo- or iodoarenes and butyllithium... 

The formation of jp -carbanions adjacent to pyridine-like nitrogen in 6-membered heteroaromatic rings is complicated by the fact that with alkyl and aryllithiums, 1,2-nucleophilic addition to the azomethine double bond (Scheme 103) normally occurs in preference to metalation [88H2659, 88MI2 88T1 90H(31)1155 91AHC(52)187]. 

In keeping with the simplicity of its structure, fluconazole can be synthesized in two steps from commercially available starting materials (Scheme 5.3). Metallation of 1-bromo-2,4-difluorobenzene with butyllithium in ether gave the corresponding aryllithium. 

Bidentate ferrocene ligands containing a chiral oxazoline substituent possess both planar chiral and center chiral elements and have attracted much interest as asymmetric catalysts.However, until recently, preparation of such compounds had been limited to resolution. In 1995, four groups simultaneously communicated their results on the asymmetric synthesis of these structures using an oxazoline-directed diastereoselective lithiation (Scheme 8.141). " When a chiral oxazolinylferrocene 439 was metalated with butyllithium and the resulting aryllithium species trapped with an electrophile, diastereomer 442 was favored over 443. The structure of the major diastereomer 442 was confirmed, either by conversion to a compound of known stereochemistry or by X-ray crystallography of the product itself or of the corresponding palladium complex. ... 

Aldehyde imines derived from alkoxyamines are metalated by LDA (0 °C, TIIF, 1 h6 or —23 °C, THF, 0.5 h13) and by potassium diethylamide, lithium bis(trimethylsily])amide and lithium 2,2,6,6-tetramethylpiperidide (—23 °C, THF, 2-4 h)1J. Nucleophilic bases such as alkyl- and aryllithium derivatives and, in some cases, alkylmagnesium bromides add to aldehyde imines. Best enantioselectivities are achieved with lithium 2,2,6,6-tetramethylpiperidide (LTMP)13. The... 

Tertiary alkyl and cycloaliphatic phosphines do not undergo alkali metal cleavage however, (aryl)3 (alkyl) P ( = 1, 2) are cleaved25 by Li/THF to give LiP(aryl)2 (alkyl) and aryllithium. Although this appears to be an attractive route to LiP(alkyl)2, it has not been widely exploited. Somewhat anomalously, PhEt2P and K produce KPEtPh and not KPEt2.27... 

LiSiCl3 was probably formed by a halogen-metal exchange reaction, when an attempt was made to couple the highly hindered aryllithium compound 43 with BrSiCl3... 

By treating fluoronanotubes with strong nucleophiles such as Grignard reagents, alkyl- and aryllithium reagents, metal alkoxides, acyl peroxides, amines and diamines, the fluorine atoms can be replaced through substitution [29, 47-50]. 

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