TMEDA

The method does not require optically pure a-pinene because 100% enantiomeric excess (ee) is achieved by crystallisation of the intermediate TMEDA-2IpcBH2 adduct, where TMEDA = (CHg )2NCH2CH2N(CH3 )2 (tetramethylethylenediamine). Other chiral monoalkylboranes derived from 2-alkyl- and 2-phenylapopinene are slightly more selective reagents as compared to monoisopinocampheylborane (66—68). 

Substituent-directed metallations are being used for the synthesis of disubstituted pyridines. A 2-substituent directs to the 3-position, and a 3-substituent usually directs to the 4-position however, in the presence of A/ A/ A[7V -tetratnethylethylenediatnine (TMEDA), 2-metallation may be achieved (12). 

Hydroc rbylComplexes. Stable homoleptic and heteroleptic thorium hydrocarbyl complexes have been synthesized. Two common homoleptic species are [Li-TMEDA]2 Th(CH2). ] [92366-18-2] (19), where TMEDA = tetramethyl ethylenediarnine, and Th(CH2CgH ) [54008-63-8] (20). 

When lithium is used as a catalyst in conjunction with a chelating compound such as tetramethylethylenediarnine (TMEDA), telomers are generally obtained from toluene and ethylene (23), where n = 010. 

Phenyllithium in ether adds to pyridazine and 6-substituted pyridazines at position 3. By using TMEDA, addition at position 4 is strongly promoted (78RTC116). 

Competitive metallation experiments with IV-methylpyrrole and thiophene and with IV-methylindole and benzo[6]thiophene indicate that the sulfur-containing heterocycles react more rapidly with H-butyllithium in ether. The comparative reactivity of thiophene and furan with butyllithium depends on the metallation conditions. In hexane, furan reacts more rapidly than thiophene but in ether, in the presence of tetramethylethylenediamine (TMEDA), the order of reactivity is reversed (77JCS(P1)887). Competitive metallation experiments have established that dibenzofuran is more easily lithiated than dibenzothiophene, which in turn is more easily lithiated than A-ethylcarbazole. These compounds lose the proton bound to carbon 4 in dibenzofuran and dibenzothiophene and the equivalent proton (bound to carbon 1) in the carbazole (64JOM(2)304). 

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

BzOCF(CF3)2, TMEDA, 20°, 30 min, 90% yield. This reagent also reacts with amines to form benzamides in high yields. 

Ni(CO)4, TMEDA, DMF, 55°, 4 h, 87-95% yield. Because of the toxicio associated with nickel carbonyl, this method is rarely used and has largeb been supplanted by palladium-based reagents. 

V,7V,7V, 7V -Tetramethylethylenediamine (TMEDA, TEMED) [110-18-9] M 116.2, b 122°, d 1.175, n 1.4153, pK 5.90, pKj 9.14. Partially dried with molecular sieves (Linde type 4A), and distd in vacuum from butyl lithium. This treatment removes all traces of primary and secondary amines and water. [Hay, McCabe and Robb J Chem Soc, Faraday Trans 1 68 1 1972.] Or, dried with KOH pellets. Refluxed for 2h with one-sixth its weight of n-butyric anhydride (to remove primary and secondary amines) and fractionally distd. Refluxed with fresh KOH, and distd under nitrogen. [Cram and Wilson 7 Am C/iem Soc 85 1245 796i.] Also distd from sodium. 

In the case of phenyllithium, it has been possible to demonstrate by NMR studies that the compound is tetrameric in 1 2 ether-cyclohexane but dimeric in 1 9 TMEDA-cyclohexane. X-ray crystal structure determinations have been done on both dimeric and tetrameric structures. A dimeric structure crystallizes from hexane containing TMEDA. This structure is shown in Fig. 7.1 A. A tetrameric structure incorporating four ether molecules forms from ether-hexane solution. This structure is shown in Fig. 7.IB. There is a good correspondence between the structures that crystallize and those indicated by the NMR studies. 

Fig. 7.2. Crystal structures of n-butyllithium. (A) (n-BuLi TMEDA)2 (B) (n-BuLi THF)4 hexane (C) [n-BuLi DME4] (D) [(n-BuLi TMEDA]. Hydrogen atoms have been omitted. (RcprcvJuccd from./ Am. Chem. Soc., 115, 1568, 1873 (1993).

Crystal structure determination has also been done with -butyllithium. A 4 1 n-BuLi TMEDA complex is a tetramer accommodating two TMEDA molecules, which, rather than chelating a lithium, link the tetrameric units. The 2 2 -BuLi TMEDA complex has a structure similar to that of [PhLi]2 [TMEDA]2. Both 1 1 -BuLi THF and 1 1 -BuLi DME complexes are tetrameric with ether molecules coordinated at each lithium (Fig. 7.2). These and many other organolithium structures have been compared in a review of this topic. ... 

Several ester enolates have also been examined by X-ray crystallography. The enolates of /-butyl propionate and /-butyl 3-methylpropionate were obtained as TMEDA solvates of enolate dimers. The enolate of methyl 3,3-dimethylbutanoate was obtained as a THF-solvated tetramer. 

Fig. 9.5. Structure of TMEDA complex of Uthium bicyclo[3.2.1]octa-2,6-dienide. (Reproduced from Ref. 121 by permission of Wiley-VCH.)...

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