Tertiary alkyllithiums

For the same reason that they resist attack at C=0 by alkyllithiums, tertiary amides can be extremely difficult to hydrolyse—almost impossible in the case of —CONPr-i2, and even —CONEt2 amides are stable to 6 M HCl for 72 h. For reactions in which an amide is not required in the product, it is preferable to use —CONEt2 and to remove the amide from the product by reduction, as in Scheme 14 (note the cooperative effect of the amide and methoxy group in the first step) . Hydrolysis can also be achieved via an imidate (see Scheme 12). 

Mioskowski et al. examined the reductive alkylation of simple epoxides by or-ganolithiums in THF in considerable detail, and found that the best yields and stereoselectivities were obtained with secondary and tertiary alkyllithiums (Table 5.2, Entries 1-5) [42]. n-BuLi gave a mixture of olefins (Entry 6), whereas PhLi and MeLi (Entries 7 and 8) gave very poor yields. Similar transformations have been reported with the use of lithium tetraalkylcerate reagents (Entries 9 and 10) [43]. 

Good yields of ketones can often be obtained by treatment of the lithium salt of a carboxylic acid with an alkyllithium reagent, followed by hydrolysis.The R group may be aryl or primary, secondary, or tertiary alkyl. Both MeLi and PhLi have been employed most often. The R group may be alkyl or aryl, though lithium acetate generally gives low yields. Tertiary alcohols are side products. 

At 62% yield, the main product of the reaction of 42b with MeLi (molar ratio 1 5.5) was l,2-dichloro-2-methylbicyclo[2.1.1]hexane (66). Again, the most probable mechanism leading to 66 is addition of MeLi to carbene 54 (X=H, X=C1), followed by lithium chlorine exchange of the intermediate tertiary alkyllithium base 67 with the trichloride 42b. An alternative mechanism, addition of LiCl to carbene 54 and methylation of the intermediate carbenoid by MeLi, formed during the reaction from MeLi and 42b, is less probable.24... 

Mechanisms of the manifold reactions of a-dialkylamino alkyllithium intermediates R(Me2N)CLiNu, formed when tertiary amides (RCONMc2) react with PhMc2SiLi followed by a second lithium reagent NuLi, have been discussed. The formation of diverse products following 1 1 insertion of an isonitrile RNC into the Li-C bond of LiCH(SiMc3)2 has been discussed. ... 

This is a catalytic-chain mechanism because the agent which adds to the olefins is regenerated in the last step.The addition reaction of the anion to the olefin is similar to the noncatalytic reaction of alkyllithium compounds with ethylene as reported by Ziegler and Gellert 37) and by Bartlett et al. 38). In this reaction (5), the less stable secondary and tertiary alkyl lithium compounds add most readily. 

In alkyllithium initiated, solution polymerization of dienes, some polymerization conditions affect the configurations more than others. In general, the stereochemistry of polybutadiene and polyisoprene respond to the same variables Thus, solvent has a profound influence on the stereochemistry of polydienes when initiated with alkyllithium. Polymerization of isoprene in nonpolar solvents results largely in cis-unsaturation (70-90 percent) whereas in the case of butadiene, the polymer exhibits about equal amounts of cis- and trans-unsaturation. Aromatic solvents such as toluene tend to increase the 1,2 or 3,4 linkages. Polymers prepared in the presence of active polar compounds such as ethers, tertiary amines or sulfides show increased 1,2 (or 3,4 in the case of isoprene) and trans unsaturation.4. 1P U It appears that the solvent influences the ionic character of the propagating ion pair which in turn determines the stereochemistry. 

It was also discovered at Phillips. that the four rate constants discussed above can be altered by the addition of small amounts of an ether or a tertiary amine resulting in reduction or elimination of the block formation. Figures 13 and 14 illustrate the effect of diethyl ether on the rate of copolymerization and on the incorporation of styrene in the copolymer. Indeed, random copolymers of butadiene and styrene or isoprene and styrene can be prepared by using alkyllithium as initiator in the presence of small amounts of an ether or a tertiary amine. 

HAY et al (12, 13) showed that the addition of TMEDA to butyl-lithium (BuLi) produces a remarkable increase in reactivity toward the polymerization of butadiene. This higher reactivity is attributed to the absence of association of alkyllithium species and the presence according to the maximum rate of polymerifcftr-tion, of a separated ion pair during the polymerization. ERUSSALIMSKY et al(14) described the anionic polymerization of isoprene in the presence of TMEDA. They showed that the tertiary diamine causes a significant increase of the polymerization rate and of the content of 3,4-links in the polymers formed, a plateau being reached for r = TMEDA/living species =4. 

The procedure described here is characterized by good yields, mild conditions, and easy synthesis of a pure form from readily available starting materials. Since tertiary aliphatic acetylenes do not form readily under these conditions, the excess of alkyllithium used is not particularly critical. The small amount of by-products that also form is similarly readily removed at the distillation stage. 

The great synthetic utility of the reaction of alkyllithium and Grignard reagents with ketonic functions has been well documented.105 These reactions take place via the intermediacy of alkoxy derivatives formed by addition of the M—C bond across the C=0 function. Hence ketones, aldehydes and formaldehyde will lead to tertiary, secondary and primary alkoxides, respectively. This type of reactivity is known for a number of other carbanionic metal alkyl derivatives, both main group and transition metals, although the synthetic utility of the reactivity has in most cases not been well documented. 

Tertiary amines such as N,N,N, N, -tetramethylethylenedia-mine (TMEDA) and l,4-diazabicyclo[2.2.2]octane strongly catalyze metallations by alkyllithium reagents. Uncatalyzed lithiation of toluene is very poor5 whereas by contrast, a yield of 90% has been obtained when TMEDA is employed as a catalyst. ... 

Two principal approaches to the synthesis of an optically pure chiral secondary or tertiary alcohol from the reaction of an organometallic reagent with an aldehyde or ketone respectively are of current interest. In the first approach an alkyllithium or dialkylmagnesium is initially complexed with a chiral reagent which then reacts with the carbonyl compound. In this way two diastereo-isomeric transition states are generated, the more stable of which leads to an enantiometic excess of the optically active alcohol. This approach is similar in principle to the asymmetric reductions discussed in Section 5.4.1 (see also p. 15). Two chiral catalysts may be noted as successful examples, (10) derived... 

Formylation of an alkyllithium (1, 280).1 Formylation of an alkyllithium or a Grignard reagent with DMF (Bouveault reaction) is generally unsatisfactory because of side reactions. However, sonication of the mixture of an alkyl or aryl halide, lithium, and DMF substantially improves the rate and the yield. The method is applicable to primary, secondary, and tertiary bromides or chlorides. Typical yields are in the range 65-85%. 

Laterally lithiated tertiary amides are more prone to self-condensation than the anions of secondary amides, so they are best lithiated at low temperature (-78 °C). N,N-Dimethyl, diethyl (416) and diisopropyl amides have all been laterally lithiated with alkyllithiums or LDA, but, as discussed in section 2.3.2.1.1, these functional groups are resistant to manipulation other than by intramolecular attack.379 Clark has used the addition of a laterally lithiated tertiary amide 417 to an imine to generate an amino-amide 418 product whose cyclisation to lactams such as 419 is a useful (if rather low-yielding) way of building up isoquinoline portions of alkaloid structures.380 The addition of laterally lithiated amines to imines needs careful control as it may be reversible at higher temperatures.381... 

It is possible to form, and cyclise, tertiary alkyllithiums, provided they are benzylic or allylic, by starting with a selenide. Krief has used selenium acetals to construct the starting materials 249 and 252, and on treatment with n-BuLi an extremely rapid (less than 20 min even at -110 °C effectively instantaneous at -78 °C) selenium-lithium exchange ensues to give tertiary organolithiums 250 and 253. Cyclisation to give 251 or 254 takes half an hour at -78 °C, and... 

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