Lithium-2,2,6,6-tetramethylpiperidide hexamethyldisilazide

Parts A and B of the procedure correspond to preparation of lithium tetramethylpiperidide, and its use in the in situ preparation and addition of dibromomethyllithium to the ester 1 producing tetrahedral intermediate 2. In Part C a mixture of lithium hexamethyldisilazide and lithium ethoxide is prepared for addition in Part D to the solution of 2. The silazide base serves to deprotonate the mono and dibromo ketones that are formed on initial warming of the reaction to -20°C, thus protecting them as the enolate anions 4 and 3. Addition of the sec-butyllithium in Part... 

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). 

The term amidolithium is the unambiguous name for the compounds RR NLi (R, R = alkyl, aryl, silyl, etc.) more often termed lithium amides. They derive their importance from the near-ubiquity of their bulkier members lithium diisopropy-lamide (LDA), lithium tetramethylpiperidide (LTMP), and lithium hexamethyldisilazide (LHMDS) in organic synthesis. Using such powerful but nonnucleophilic bases, many useful reactions may be performed, notably the enolization of ketones and esters, which can proceed both regio- and stereoselectively under kinetic control at low temperatures. ... 

What is needed for the alkylation is rapid conversion of the ester into a reasonably stable enolate, so rapid in fact that there is no unenolised ester left. In other words the rate of proton removal must be faster than the rate of combination of enolate and ester. These conditions are met when lithium enolates are made from esters with lithium amide bases at low temperature, often 78 °C. Hindered bases must be used as otherwise nucleophilic displacement will occur at the ester carbonyl group to give an amide. Popular bases are LDA (Lithium Di-isopropyl Amide, 66), lithium hexamethyldisilazide 67, and lithium tetramethylpiperidide 68, the most hindered of all. These bases are conveniently prepared from the amine, e.g. 65 for LDA, and BuLi in dry THF solution. 

LDA = lithium diisopropylamide LICA = lithium isopropylcyclohexylamide LHMDS = lithium hexamethyldisilazide LTMP = lithium tetramethylpiperidide... 

The lithium enolate generated using lithium diisopropylamide [4111-54-0], lithium 2,2,6,6-tetramethylpiperidide [58227-87-1], or lithium hexamethyldisilazide [4039-32-17 is a chemical reagent that reacts with other reactants to give a variety of products (37). In the quest for improved stereospecificity, enolates with different cations such as silicon, aluminum, boron, and zinc have also been used (38). In group transfer polymerization, ketene silyl acetals, eg, (CH3)2C=C [OSi(CH3)3] (OCH3) are employed as initiators (39). 

This asymmetric induction is strongly affected by the base. Asymmetric methylation of 32 occurred with retention of configuration when lithium 2,2,6,6-tetramethylpiperidide (LTMP) or LDA was used, while inversion of configuration was observed with potassium hexamethyldisilazide (KHMDS)... 

LTMP = lithium 2,2,6,6-tetramethylpiperidide (17). LHDS = lithium hexamethyldisilazide (18). 

Lithium cyclohexylisopropylamide Lithium diisopropylamide Lithium hexamethyldisilazide Lithium 2,2,6,6-tetramethylpiperidide Methylaluminum fcis-(4-bromo-2,6-di-teri-butylphenoxide) fci5-(2,6-di-terf-butyl-4-methylphenoxy)methyl aluminum wefa-Chloroperoxybenzoic acid... 

---