Hindered lithium amide

Use of LTMP as base [52] in situ with Me3SiCl allows straightforward access to a variety of synthetically useful a, 3-epoxysilanes 232 at near ambient temperature directly from (enantiopure) terminal epoxides 231 (Scheme 5.55) [81]. This reaction relies on the fact that the hindered lithium amide LTMP is compatible with Me3SiCl under the reaction conditions and that the electrophile trapping of the nonstabilized lithiated epoxide intermediate must be very rapid, since the latter are usually thermally very labile. 

A priori borataethenes would be expected to be much more stable than the corresponding boraethenes because, as Rundle presciently noted about organometallic structures,50 all low-lying atomic orbitals are involved in the bonding. In fact, the stabilization of 52 is the driving force for the acidity of C—H bonds of proper orientation a to tricoordinate boron. Such acidity was first detected by Rathke and Kow through the treatment of B-methyl-9-borabicyclo[3.3.1] nonane (53) with hindered lithium amides, such as lithium 2,2,6,6-tetramethylpiperidide51 (Eq. 18) ... 

Under conditions of kinetic control, the mixed Aldol Addition can be used to prepare adducts that are otherwise difficult to obtain selectively. This process begins with the irreversible generation of the kinetic enolate, e.g. by employing a sterically hindered lithium amide base such as LDA (lithium diisopropylamide). With an unsymmetrically substituted ketone, such a non-nucleophilic, sterically-demanding, strong base will abstract a proton from the least hindered side. Proton transfer is avoided with lithium enolates at low temperatures in ethereal solvents, so that addition of a second carbonyl partner (ketone or aldehyde) will produce the desired aldol... 

Hydrocarbon solutions of n-, 5- and r-BuLi re the ultimate source of most organolithiums, but a number of other bases are widely used to generate organolithiums from more acidic substrates. Among these are LDA, LiTMP and other more hindered lithium amide bases, and hindered aryllithiums such as mesityllithium and triisopropylphenyllithium. 

Lithium enolates are usually made at low temperature in THF with a hindered lithium amide base (often LDA) and are stable under those conditions because of the strong O-Li bond. The formation of the enolate begins with Li-O bond formation before the removal of the proton from the a position by the basic nitrogen atom. 

Now we can make the kinetic lithium enolate with a hindered lithium amide base. In fact, the one chosen here was even more hindered than LDA as it has two MejSi groups on the nitrogen atom. 

The reaction of terminal epoxides with hindered lithium amide bases followed by organometallic reagents generates alkenes <2004JA12250>. Related reactions are the formation of enamines <2004JA6870> from terminal epoxides, 2-ene-l,4-diols from terminal epoxides <20050L2305>, and allylamines from amino epoxides <20060L349>. 

Bonm-alabilized earbanions. Ordinarily bases coordinate with the boron atom of organoboranes. However, Rathke and Row report that a highly hindered lithium amide such as lithio-2,2,6,6-tetramcthylpiperidine or lithio-t-butylneopentylamine can remove the a-proton from an organoborane to generate earbanions. Thus treatment of the boron compound B-tnethyl-9-borabicyclononane (1) in benzene with the former base for 12 hr. at room temperature followed by quenching with deuterium oxide results in deuterium incorporation of 50% (equation I). 

Tetramethylpiperidlne, purchased from Tokyo Kasei Kogyo Company, Ltd. or Aldrich Chemical Company, Inc., was used. The use of this sterically-hindered lithium amide is crucial for high diastereoselectivlty. If lithium diisopropyl amide Is used, the diastereoselectivlty of the reaction... 

The first thermally stable di-co-ordinated C—P=N system (175) has been prepared utilizing transamination reactions undergone by aminoiminophos-phines on treatment with highly hindered lithium amides. This compound is an orange-red liquid that is stable to distillation under reduced pressure but which... 

However, the most common route to metal-imido compounds is some type of fv-elimination. For example, imido complexes have been prepared by the addition of amine or alkali metal amides to a metal halide (Equations 13.54 and 13.55). This reaction most likely occurs through an a-elimination from an amido halide intermediate. In addition, the first low-valent, late-transition-metal-imido complex was prepared by the simple reaction of [Cp rCyj with hindered lithium amides (Equation 13.56). - ... 

A remarkable synthetic route to enamines, based on the reaction of terminal epoxides with hindered lithium amides, has been disclosed by Hodgson and co-workers (2004JA6870). When racemic lithium 2,2,6-trisubstituted piperidine 26 (R = Et) is reacted with terminal epoxides 25, trisubstituted piperidine-derived enamines 27 are formed in yields of up to 83%. The latter exhibited efficient C-alkylation activity toward a... 

Terminal epoxides 29 have also been proven to efficiently undergo a dimerization reaction promoted by hindered lithium amides, thereby leading to 2-ene-l,4-diols 30 as the final products. Such a reaction, which exploits the carbenoid character of Hthiated oxiranes, works at best when neat terminal epoxides are slowly added to a hexane/i-BuOMe mixture of lithium amide (Scheme 7). The synthetic utiHty of this methodology has been illustrated for the synthesis of D-mannitol and D-iditol in only three steps starting from chiral non-racemic (S)-tritylglycidyl ether (20050L2305). 

Nonnucleophibc (sterically hindered) lithium amides can be prepared by the simple reaction of the corresponding amines with -BuLi in nonpolar organic solvents (Fig. 26.3). Lithium amides are more soluble in hydrocarbons than their heavier element congeners (Na, K). LiN(i-Pr)j (LDA) is also cheaper than KN(/-Pr)2 (KDA) and is more widely used. Lithium amides, which have a much lower Lewis acid character than alkyllithiums, also form aggregates in solution [26-28]. They usually react under thermodynamic control according to a classic acid-base mechanism. The p a of diisopropylamine is 36 [8]. Lithium 2,2,6,6-tetramethylpiperidide (LTMP) is slightly more basic... 

To achieve more efficient direct methylation of lactic acid, the hindered lithium amide supported by cross-linked polystyrene was prepared from commercially available Merrifield resin. Obtained pol5mier-supported hindered lithium amide/methyl iodide system was found to be an efficient condition for the a-methylation reaction of lactic acid derivatives, giving excellent 3delds of a-methylated products (98%) under room temperature for a very short reaction time [101]. 

Watanabe, K, Ando, Y, Shirai, Y, and Nishida, H. (2013). A cross-linked polystyrene supported hindered lithium amide as a deprotonation reagent for a-methylation of lactic acid. Tetrahedron Lett, 54, 4320-4323. 

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