Chromium-arene complexes, lithiation

Desymmetrisation by enantioselective ortholithiation has been achieved with ferrocenylcarboxamides 434,187 and also (with chiral lithium amide bases) a number of chromium-arene complexes.188 The chromium arene complex 435, on treatment with s-BuLi-(-)-sparteine, gives 436 enantioselectively, and reaction with electrophiles leads to 437. However, further treatment with r-BuLi generates the doubly lithiated species 438, in which the new organolithium centre is more reactive than the old, which still carries the (-)-sparteine ligand. Reaction of 438 with an electrophile followed by protonation therefore gives ent-431.m... 

SCHEME 26.14 Asymmetric lithiation of chromium arene complexes. 

The first enantioselective functionalization of tricarbonylchromium arene complexes using chiral bases, to generate planar chiral chromium complexes, was reported by Simpkins and coworkers in 1994 and involved a directed orf/zo-lithiation and subsequent quench with an electrophile78. Both aromatic and benzylic functionalization of tricarbonylchromium arene complexes has been achieved. 

The advantage of using lithiated arene complexes of chromium as starting materials to synthesize o-,7r-bimetallic complexes of chromium and manganese was clearly demonstrated by reacting (77 -o-C6H4XLi)Cr(CO)3 (X = H, F) with Mn(CO),Br (305). The products, (77< -C6H4XC(0) Mn-... 

The synthesis of an enantiomerically enriched chromium complex via asymmetric lithiation of a prochiral tricarbonyl(ri -arene)chromium complex using a chiral lithium amide base was first demonstrated in 1994 by Simpkins [88]. Arene complex 44 was treated with C2-symmetric chiral base ent-39 in the presence of TMSCl as an internal quench and silylated complex 45 was obtained in 84% ee (Scheme 24). 

For monosubstituted arenes, kinetically controlled discrimination between the two enantiotopic ortho hydrogens of the planar chiral benzene chromium tricarbonyl complex leads to nonracemic products. Asymmetric lithiation is more efficient when one or more oxygen atoms, such as ether linkages, are present in the starting prochiral complex (Scheme 26.14). Treatment of Cr(CO)j-anisole complex 52 with the chiral lithium amide 53, in the presence of TMSCl under ISQ conditions, affords (+)-orfho-silylated complex 54 with good chemical yield and ee value [143-145]. The isobenzofuran system 55 reacts as well to give a-sUylated product 56 [146]. 

Lithiation. With anisole, fluorobenzene, and chlorobenzene chromium complexes, lithiation always occurs at an ortho position of the substituents under mild conditions (eqs 14 and 15). Protected phenol or aniline chromium complexes with sterically bulky substituents produce meta lithiation exculsively. The lithi-ated position of some (arene)chromium complexes (3) differs from that of the corresponding chromium-free compounds (4). ... 

A 1,2 or 1,3 unsymmetrically disubstituted arene is prochi-ral and therefore the corresponding chromium tricarbonyl compounds are chiral. (Substituted arene) complexes with amine, carboxyl, and formyl groups at the ortho position are resolved into optically active chromium complexes through corresponding diastereomeric adducts (eq 25). Biocatalysts also perform the kinetic resolution of racemic chromium complexes (eq 26). The optically active chromium complexes can be prepared by di-astereoselective ortho lithiation of the chiral benzaldehyde or acetophenone acetal complexes, and diastereoselective chromium complexation of the chiral ort/io-substituted benzaldehyde am-inals (eq 27). Catalytic asymmetric cross-coupling of meso (1,2-haloarene)chromium complex produces chiral monosubstituted complexes. The chiral (arene)chromium complexes can be used as ligands in asymmetric reactions. ... 

Arasabenzene, with chromium, 5, 339 Arcyriacyanin A, via Heck couplings, 11, 320 Arduengo-type carbenes with titanium(IV), 4, 366 with vanadium, 5, 10 (Arene(chromium carbonyls analytical applications, 5, 261 benzyl cation stabilization, 5, 245 biomedical applications, 5, 260 chiral, as asymmetric catalysis ligands, 5, 241 chromatographic separation, 5, 239 cine and tele nucleophilic substitutions, 5, 236 kinetic and mechanistic studies, 5, 257 liquid crystalline behaviour, 5, 262 lithiations and electrophile reactions, 5, 236 as main polymer chain unit, 5, 251 mass spectroscopic studies, 5, 256 miscellaneous compounds, 5, 258 NMR studies, 5, 255 palladium coupling, 5, 239 polymer-bound complexes, 5, 250 spectroscopic studies, 5, 256 X-ray data analysis, 5, 257... 

Arenes and heteroarenes which are particularly easy to metalate are tricarbo-nyl( 76-arene)chromium complexes [380, 381], ferrocenes [13, 382, 383], thiophenes [157, 158, 181, 370, 384], furans [370, 385], and most azoles [386-389]. Meta-lated oxazoles, indoles, or furans can, however, be unstable and undergo ring-opening reactions [179, 181, 388]. Pyridines and other six-membered, nitrogen-containing heterocycles can also be lithiated [59, 370, 390-398] or magnesiated [399], but because nucleophilic organometallic compounds readily add to electron-deficient heteroarenes, dimerization can occur, and alkylations of such metalated heteroarenes often require careful optimization of the reaction conditions [368, 400, 401] (Schemes 5.42 and 5.69). 

Keywords Lithiation Arene-chromium complexes Aryl-lithium Regioselectivity in arene lithiation... 

The dioxane moiety of the arene chromium complex (53) promotes ort/io-lithiation, facilitating the synthesis of o-substituted benzaldehydes. The reaction with electrophiles affords a single diastereoisomer as the only product <97JOC8264>. 

Planar chiral compounds usually (and for the purpose of this review, always) contain unsymmetrically substituted aromatic systems. Chirality arises because the otherwise enantiotopic faces of the aromatic ring are differentiated by the coordination to a metal atom - commonly iron (in the ferrocenes) or chromium (in the arenechromium tricarbonyl complexes). Withdrawal of electrons by the metal centre means that arene-metal complexes and metallocenes are more readily lithiated than their parent aromatic systems, and the stereochemical features associated with the planar chirality allow lithiation to be diastereoselective (if the starting material is chiral) or enantioselective (if only the product is chiral). 

Another interesting application of arene group activation by chromium complex formation is found in the facile metallation of coordinated arene moieties with lithium, the lithiated complex being activated towards subsequent substitutions by electrophilic reagents. This principle has been applied to the synthesis of anthracyclone analogues [5e]. 

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