Lead diisopropylamide

LDA, see Lithium diisopropylamide LDL, heart disease and, 1090-1091 Le Bel, Joseph Achille, 7-8 Leading strand, DNA replication and, 1107... 

Stereodivergent aldol addition is also possible when (.S,)-5,5-dimethyl-4-trimethylsiloxy-3-hexanonc (16) is chosen as the enolate precursor. Thus, the lithium enolate generated from 16 by treatment with lithium diisopropylamide and tetramethylethylenediamine leads predomi-... 

Metalation ofa-sulfinyl dimethylhydrazones with terf-butylmagnesium bromide, butyllithium or lithium diisopropylamide, and reaction of the generated azaenolates with aldehydes, provides aldol adducts (e.g., 6) as mixtures of diastereomers. Reductive desulfurization leads to fi-hydroxy dimethylhydrazones (e.g., 7) which are cleaved to the desired /(-hydroxy ketones in 25% overall yield10 u. The enantiomeric excesses are about 50%, except for (- )-3-hydroxy-4-methyl-1-phenyl-1-pentanone (8) which was obtained in 88% ee. 

When 2,2-dimethylpropanal is used to prepare the azomethine moiety, the corresponding azaallyl anion may be obtained when l,8-diazabicyclo[5.4.0]undec-7-ene/lithium bromide is used as base. The subsequent addition to various enones or methyl ( )-2-butenoate proceeds with anti selectivity, presumably via a chelated enolate. However, no reaction occurs when triethylamine is used as the base, whereas lithium diisopropylamide as the base leads to the formation of a cycloadduct, e.g., dimethyl 5-isopropyl-3-methyl-2,4-pyrrolidinedicarboxylate using methyl ( )-2-butenoate as the enone84 89,384. 

Secondary amines, such as pyrrolidine, must be alkylated with care too polar a solvent leads to participation of a second nearby polymer-bound alkylant in the formation of a quaternary ammonium salt, along with the desired immobilized trialkyl amine. The exception, as seen above, is diisopropylamine, which refuses to displace tosylate even in the refluxing pure amine, or in hot dimethyl-formamide or other polar solvent, while metal diisopropylamide is notorious as a powerful non-nucleophilic base. However, carboxamide is not difficult to form from (carboxymethyl)polystyrene, again using toluenesulfonyl chloride as condensing agent this can then be reduced to (diisopropyl-ethylaminoethyl)polystyrene, which is of interest as a polymer-bound non-nucleophilic base. ... 

Tricyclic lactams, such as exo- and c r/n-3a,4,7,7a-tetrahydro-4,7-methano-2-phenyl-1 //-isoin-dolc-1,3(2//)-dione (4), have been transformed into their dianions by treatment with slightly more than two equivalents of lithium diisopropylamide in tetrahydrofuran, sometimes with hexamethylphosphoric triamide as cosolvent. Alkylation with iodomethane or the bifunctional 1,4-dibromobutane leads to dialkylated products2. 

The regioselectivity of the latter reaction is strongly dependent on the base used for deprotonation. Thus, reaction with lithium diisopropylamide in tetrahydrofuran/hexamethylphosphoric triamide results in selective endo metalation23 and leads to the bicyclic product 10. 

The treatment of thiazole with n-butyl- or phenyllithium leads to exclusive deprotonation at C-2. When the 2-position is blocked, deprotonation occurs selectively at C-5. However, if the substituent at C-2 is an alkyl group, the kinetic acidities of the protons at the a-position and at the 5-position are similar. The reaction of 2,4-dimethylthiazole with butyllithium at -78°C yields the 5-lithio derivative (289) as the major product but if the reaction is carried out at higher temperature the thermodynamically more stable 2-lithiomethyl derivative (290) is obtained (Scheme 37). The metallation at these two positions is also dependent on the strength and bulk of the base employed (74JOC1192) lithium diisopropylamide is preferred for selective deprotonations at the 5-position. 

However for the formation of optically active a-alkyl aldehydes, the imine or hydrazone routes have proved of considerable value.122 In the preparative example123 the aldehydes propanal and octanal are converted with (S)-( — )-2-amino-l-methoxy-3-phenylpropane (14) into the imines (15) and (16) respectively. Treatment with lithium diisopropylamide then yields the corresponding lithioenamines [only the (fs)-isomers are formulated, since the (Z)-isomers would be less stable]. These intermediates have a topography which determines the subsequent direction of attack by the alkyl halide (see also Section 5.11.7, p. 688). In the formulation below, this stereoselection is from above the plane of the paper and leads to the (/ )- and (S)-2-methyloctanals respectively. 

The reactivity of 1,3-ditellurole has been inadequately investigated. Lithiation of the simplest 1,3-ditelluroles with lithium diisopropylamide (LDA) leads (depending on their structure) to either 2- or 4(5)-lithio derivatives (83TL237). Thus, 4-lithio-l, 3-ditellurole 57 is formed from 1,3-ditellurole, whereas lithiation of its 4-phenyl derivative produces 2-lithio-4-phenyl-l,3-ditellurole 58. The latter result is explained by the steric hindrance that the 4-phenyl substituent creates for the attack of LDA at position 5 of the five-membered ring. 

Esters of 2-(2-methylphenyl)hydrazinecarboxylic acids can be metallated with lithium diisopropylamide (LDA) and the resulting polyanions condensed with aromatic esters and lead to acid-catalysed cyclization to 1-isoquinolones... 

Equimolar amounts of lithium diisopropylamide (LDA) and tin hydrides reacted in THF to form diisopropylamine and the corresponding stannyllithium (equation 12)27,28. In diethyl ether or hexane, an excess of tin hydride was required for complete reaction which leads to the ditin compound and lithium hydride (equation 13). 

Eliminations of epoxides lead to allyl alcohols. For this reaction to take place, the strongly basic bulky lithium dialkylamides LDA (lithium diisopropylamide), LTMP (lithium tetramethylpiperidide) or LiHMDS (lithium hexamethyldisilazide) shown in Figure 4.18 are used. As for the amidine bases shown in Figure 4.17, the hulkiness of these amides guarantees that they are nonnucleophilic. They react, for example, with epoxides in chemoselective E2 reactions even when the epoxide contains a primary C atom that easily reacts with nucleophiles (see, e.g., Figure 4.18). 

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