Metal-arene complexes, lithiation

By coordinating to arenes, transition metals can facilitate ring lithiation by decreasing the electron density in the ring and acidifying the ring protons. We shall consider briefly the two most important metal-arene complexes in this regard—arenechromium tricarbonyls and ferrocenes. 

Semmelhack MF (1995) Transition metal arene complexes ring lithiation. In Abel EW, Stone EGA, Wilkinson G (eds) Comprehensive organometallic chemistry II. Pergamon... 

Since different reactivity is observed for both the stoichiometric and the catalytic version of the arene-promoted lithiation, different species should be involved in the electron-transfer process from the metal to the organic substrate. It has been well-established that in the case of the stoichiometric version an arene-radical anion [lithium naph-thalenide (LiCioHg) or lithium di-ferf-butylbiphenylide (LiDTBB) for using naphthalene or 4,4 -di-ferf-butylbiphenyl (DTBB) as arenes, respectively] is responsible for the reduction of the substrate, for instance for the transformation of an alkyl halide into an alkyllithium . For the catalytic process, using naphthalene as the arene, an arene-dianion 2 has been proposed which is formed by overreduction of the corresponding radical-anion 1 (Scheme 1). Actually, the dianionic species 2 has been prepared by a completely different approach, namely by double deprotonation of 1,4-dihydronaphthalene, and its X-ray structure determined as its complex with two molecules of N,N,N N tetramethylethylenediamine (TMEDA). ... 

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). 

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]. 

MO calculations suggest that, in nucleophilic addition reactions of substituted benchrotrenes [( -PhX)Cr(CO)3] (see Vol. 9, ref. 412), the preferred orientation of addition is influenced more by the conformation of the Cr(CO)a residue than by the electronic character of the substituent X. Whereas lithiation (with BuLi-TMED) of 3-methoxybenzyl alcohol occurs very predominantly at the 2-position of the arene ring, similar treatment of the corresponding n-Cr(CO)3 complex gives a mixture of the 2- and 4-lithio derivatives in the ratio 23 77, respectively these products were characterized by isolation of carboxylic acid derivatives following carbonation (COg) and metal decomplexation hv 0. Experimental details for the preparation of [(iy-PhX)Cr(CO)3] (X=I and SiMes) from [( -PhLi)Cr(CO)3] have been reported. This lithio derivative has also been used to prepare the carbene complexes [(OC)3Cr(i7-Ph)C(OEt)M(CO)5] (M=Cr, Mo, and W), which react with BX, (X=C1 and Br) to give the carbyne products [(OC)3Cr( Ph)C=M(CO)4X] (M=Cr and W only). ... 

---