TMEDA lithium

The molecular structure of (TMEDA)lithium tetramethylarsolide resembled the characteristic features of the carbon analogues such as 7] -coordination <1999CRV969>. The differences of molecular and crystal structures of the arsolides 11a (M = alkali metal) and the stibolides 11b (M = alkali metal) of the heavier alkali metals are dominated by the differences of the radii of the metal atoms and of the pnictogen atoms. In Table 2, the radii of the relevant atoms are listed <20040M3417>. 

Lithium-aryls are dimers or tetramers depending on the solvent (ether resp. TMEDA). Lithium-benzyl is a monomer, and lithium-allyl has a zigzag chain structure with one coordinated ether molecule bonded to each lithium. 

Typical experimental procedure for (S)-3-(l,3-dioxo-l,3-dihy-dro-isoindol-2-yl)-3-fluoro-2-oxo-piperidin-l-carboxylic acid tert-butyl ester (precursor of 3S-fluorothalidomide) using the dihydroquinine/NFSI combination with TMEDA Lithium bis (trimethylsilyl)amide solution l.OM in THF (0.087mL, 0.087 mmol) was added to the solution of 3-(l,3-dioxo-l,3-dihydro-iso-indol-2-yl)-2-oxo-piperidin-l-carboxylic acid tert-hutyl ester (20 mg, 0.058 mmol) and tetramethylethylenediamine (0.013 mL, 0.087 mmol) in THF (l.OmL) at -80°C under Ar. After being stirred for 0.5 hours, the suspension of the dihydroquinine/NFSI combination [the solution of dihydroquinine (28.4 mg, 0.087 mmol) and N-fluorobenzenesulfonimide (27.4 mg, 0.087 mmol) in THF (2.0 mL) was stirred for 1 hour at room temperature under Ar] was dropwise and then stirred for overnight at -80 °C. The reaction was quenched with IN hydrochloric acid, extracted with ethyl acetate, washed with brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified by silica-... 

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. 

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. 

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. ... 

Trialkylsilanes are usually formed by the addition of a lithium or Grignard reagent to the silyl chloride, and thus, discussions related to the formation of the silyl acetylene bond will be kept to a minimum. Silyl acetylenes are prepared from the alkynylcopper(I) reagents in the presence of PPh3, Zn or TMEDA in CH3CN at 100°, 36-98% yield. It is interesting to note that the... 

Deprotonation of alkenes by butyllithium in the presence of TMEDA affording, for example, 2-propenyllithium from propene14, (2-methyl-2-propenyl)lithium from 2-methylpropene31,... 

Several reviews cover hetero-substituted allyllic anion reagents48-56. For the preparation of allylic anions, stabilized by M-substituents, potassium tm-butoxide57 in THF is recommended, since the liberated alcohol does not interfere with many metal exchange reagents. For the preparation of allylic anions from functionalized olefins of medium acidity (pKa 20-35) lithium diisopropylamide, dicyclohexylamide or bis(trimethylsilyl)amide applied in THF or diethyl ether are the standard bases with which to begin. Butyllithium may be applied advantageously after addition of one mole equivalent of TMEDA or 1,2-dimethoxyethane for activation when the functional groups permit it, and when the presence of secondary amines should be avoided. 

Table 1. l-(Diisopropylaminocarbonyloxy)-2-alkenyl-lithium-TMEDA Complexes by Deprotonation of Achiral or Racemic 2-Alkenyl Diisopropylcarbamates with Butyllithium (Selected Examples)... 

The lithium-TMEDA complex 1, obtained by deprotonation of (S)-(E)-1 -methyl-2-butenyl diisopropylcarbamate (84% ee), affords, after metal exchange by tetraisopropoxytitanium and addition to 2-methylpropanal, the homoaldol adduct ( + )-4 with 73% ee, whereas (-)-4 (53 % ee) is obtained when chlorotris(diethylamino)titanium is used104. 

The reagents prepared by lithiation (see Section 1.3.3.3.1.2.) and titanium exchange of (S)-(Z)-l-methyl-2-butenyl diisopropylcarbamate106 show a diminished reactivity when compared with those derived from the ( -isomer, indicating that in both metalation steps the doublebond geometry is retained16. After treatment of the lithium -TMEDA complex with chlorotris-(diethylamino)titanium and 2-methylpropanal, the homoaldol adduct (3S,47f)-(Z)-4-hydroxy-1,3,5-trimethyl-l-hexenyl diisopropylcarbamate [( + )-4], is formed with 88% ee16. 

The monolithium salt of 4-hydroxy-4-(phenylethynyl)-2.5-cyclohexadienone (12), prepared in situ by the addition of lithium acetylide to /7-benzoquinone, was treated with methylmagnesium chloride in l HF-TMEDA or in THF —DMPU. The syn-, 4-addition adduct 13, derived from intramolecular delivery of the carbon nucleophile by the hydroxy oxygen, as well as the <7s-1,4-diol 14, obtained via intermolecular 1,2-addition, were obtained in varying amounts depending on the conditions. The selectivity on 1,4- to 1,2-addition increased by the addition of cation chelating agents such as DMPU, TMEDA, and 15-crown-5. Although the 1,4 to 1,2... 

The viscometric findings of Young 1211 who investigated the effect of tetramethyl ethylene diamine (TMEDA) addition on the viscosity of butadiene capped lithium polystyryl solutions showed that the results did not agree with those expected on the basis of the reaction... 

The results reported by Helary and Fontanille 84) provide an illustration of the above principles. Coordination of lithium polystyrene in cyclohexane by TMEDA increases the propagation rate for c = 8.3 mM but decreases for c = 0.92 mM. This is seen in the plots shown in Fig. 22. 

Say that at c = 1 mM the propagation rate is not affected by the addition of TMEDA, a reasonable assumption based on the data of Helary and Fontanille. This leads to ktKigs = 0.84 10-2 M1/2 sec-1 as derived from the equation c = k2Kdiss/8k, whereas its value determined from the kinetics of lithium polystyrene polymerization in cyclohexane is 0.7 102 M1/2 sec-1. The agreement is fair. Note, the results are independent of the value of Kso). 

An interesting approach to studies of the effects of coordination on the reactivity of lithium polydienes in hydrocarbon solvents was developed by Erussalimski and his colleagues 151 154 The polymerization of lithium polyisoprene in hexane is accelerated by the addition of TMEDA152), the rate levels off at a value of R = [TMEDA]/[li-thium polyisoprene] of 8, its final value giving the absolute rate constant of propagation of the polyisoprene coordinated with TMEDA, namely 0.17 M7l s at 20 °C. 

Investigation of the polymerization at a low value of R = 0.01 allows the observation of two simultaneously proceeding propagations, one involving the unassociated lithium polyisoprenes and the other due to those coordinated with TMEDA, provided that both contribute comparably to the growth. This is claimed by the authors. Indeed, examination of their data indicates that 10% of the polyisoprene formed... 

In the low molecular weight fraction a relatively high content of the 3,4-linkages is formed, characteristic of the polymers produced in the presence of TMEDA. On this basis it was concluded that the unassociated polymers coordinated with TMEDA propagate more slowly than those unassociated and non-coordinated with the diamine, a conclusion concordant with the previously discussed findings of Fontanille84) and confirmed by Schue, 55> for lithium polyisoprene. 

Finally it should be stressed that the complexation affects the microstructure of poly dienes. As was shown by Langer I56) small amounts of diamines added to hydrocarbon solutions of polymerizing lithium polydienes modify their structure from mainly 1,4 to a high percentage of vinyl unsaturation, e.g., for an equivalent amount of TMEDA at 0 °C 157) the fraction of the vinyl amounts to about 80%. Even more effective is 1,2-dipiperidinoethane, DIPIP. It produces close to 100% of vinyl units when added in equimolar amount to lithium in a polymerization of butadiene carried out at 5 °C 158 159), but it is slightly less effective in the polymerization of isoprene 160>. 

The frequently used starting material Li(TMEDA)[PhC(NSiMe3)2] was found to be monomeric in the solid state. Monomeric molecular structures were also established for lithium amidinates containing very bulky terphenyl or triptycenyl... 

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