Secondary alkyllithiums

Naphthyl sulphones 116 are susceptible to nucleophilic attack at the 2-position of the naphthalene ring by the alkyllithiums" " secondary sulphonamides 117, on the other hand, undergo perilithiation with alkyllithiums (Scheme 50) °. 

The yield can probably be increased by carrying out the reaction in an ether solvent with an alkyllithium as base, but the simplicity and relative ease of the conditions described appear to make the possible yield advantage secondary. 

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. 

Organolithium reagents in which the carbanion is delocalized are more useful than alkyllithium reagents in alkylation reactions. Allyllithium and benzyllithium reagents can be alkylated and with secondary alkyl bromides and a high degree of inversion of configuration is observed.78... 

The synthesis of alkali metal organophosphides and arsenides is usually most conveniently achieved by the direct metalation of a primary or secondary phosphine/arsine with a strong deprotonating agent such as an alkyllithium or an alkali metal hydride ... 

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. 

The classical preparation of alkyllithium compounds by reductive cleavage of alkyl phenyl sulfides with lithium naphthalene (stoichiometric version) was also carried out with the same electron carrier but under catalytic conditions (1-8%). When secondary alkyl phenyl sulfides 73 were allowed to react with lithium and a catalytic amount of naphthalene (8%) in THF at —40°C, secondary alkyllithium intermediates 74 were formed, which finally reacted successively with carbon dioxide and water, giving the expected carboxylic acids 75 (Scheme 30) °. 

The enantioselective addition of alkyllithium to aldehyde in the presence of the lithium salt of diaminoalcohol (94) yielded optically active secondary alcohols as shown in Table 2. 

Common synthetic routes to beryllium amides, which were summarized in Ref. 1, involve the direct or indirect amination of beryllium hydride, beryllium chloride, a beryllium alkyl or amide precursor. Beryllium amides with bulky substituents are generally synthesized via the trans-metallation of beryllium dichloride with the lithium amides. The reaction of beryllium dichloride with secondary amines in the presence of an alkyllithium represents a less common synthetic route to beryllium amides. The formation ofbery Ilium amides via the reaction of an alkyl beryllium as well as beryllium hydride species with amines is also known. ... 

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. 

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... 

A second cognate preparation in Expt 5.94 describes a general procedure for the conversion of /V,/V-dimethylcarboxamides into ketones by reaction with primary alkyllithiums.127c As the reaction is not successful with secondary alkyllithiums, a branched chain ketone such as 4-methylheptan-3-one is prepared from ethyllithium and /V,/V,2-trimethylpentanamide, and not from 2-pentyllithium and N,N-dimethylpropanamide. 

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%. 

The addition of amines and ethers to alkyllithium compounds profoundly affects polymerization of such species. Amines and ethers alter the association of RLi compounds and change the course of the polymerization and its kinetics. Also, the presence of small amounts of such impurities as water, alcohols, or a-acetylenes, influences the kinetic chain length. The chain-termination reaction with such acidic protons is almost instantaneous. However, there are certain types of protons, such as a-aromatic, secondary amine, and /3-acetylenic, that are not acidic enough to react immediately but will undergo transmetalation during the course of a polymerization reaction. This results in termination or chain transfer of the polymer chain, and limits the realization of polymers of... 

However, the decrease in rate was initially explained by the difference in reactivity of the alkyllithiums present, i.e., whether or not a primary or secondary anion was involved. Yet, the propagation reaction was quite different because the structure of the active species did not vary after the addition of the first ethylene unit. The fact that the constant rate (the rate after 1 mole of ethylene is consumed per mole of BuLi) varied linearly with initiator concentration at TMEDA /-BuLi = 1.0 indicated that a monomeric complex was responsible for the propagation reaction (PELi-TMEDA) [Eqs. (13), (14)]. 

In the presence of HMPT the anion of 3 undergoes a [2,3]Wittig rearrangement to provide an unstable aldehyde, which is trapped by an alkyllithium to give (E)-homoallylic secondary alcohols (5). 

A,A-Dimethylbenzamides can be used as lithiation directors even under conditions that lead to alkyllithium attack at the carbonyl group to give ketones. The tetrahedral intermediate in this sequence 196 is a good director of lithiation (note its similarity to a deprotonated secondary amide) and an excess of organolithium intercepts this intermediate and... 

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... 

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