LiHMDS, lithium hexamethyldisilazid

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). 

LiHMDS lithium hexamethyldisilazide PPTS pyridinium p-toluenesulfonate... 

The 6Li, 15N and 13C NMR spectra of the a-aminoalkoxide-LiHMDS mixed dimer, where LiHMDS = lithium hexamethyldisilazide, showed the presence of a pair of conformers.7 6Li and 15N couplings and 6Li, ll HOESY data gave structural information for chiral lithium amides with chelating sulfide groups, e.g. (3).8... 

Tertiary A-allylthioamides have been converted into thioamidium salts by the formation of complexes with Lewis acid. Further treatment with lithium hexamethyldisilazide (LiHMDS) affords the corresponding 1,2-disubstituted pyrroles (Scheme 25).52... 

Vedejs et al. developed a method for the iodination of oxazoles at C(4) via 2-lithiooxazoles by exploiting the aforementioned equilibrium between cyclic (5) and acyclic (6) valence bond tautomers of 2-lithiooxazole [4]. When 5-(p-tolyl)oxazole (8) was treated with lithium hexamethyldisilazide (LiHMDS) in THF followed by treatment with 1,2-diiodoethane as the electrophile, 2-iodooxazole 9 was obtained exclusively. On the other hand, when 50 volume% of DMPU was added prior to the addition of the base, 4-iodooxazole 10 was isolated as the predominant product (73%) with ca. 2% of 9 and ca. 5% of the 2,4-diiodooxazole derivative. 

In solution, lithium hexamethyldisilazide (LiHMDS) is a strong enough base to deprotonate esters, ketones, and alcohols, with a pK of about 27 in DMSO solvent. In the gas phase, the bare anion is too weak to deprotonate methanethiol, much less the ketones, esters, and comparable carbon acids. The change in relative anionic basicity is on the order of 14 kcal/mol. 

An elegant cyclization-cleavage strategy has been devised for the removal of resin-bound 1,3-amino alcohol derivatives 392 as l,3-oxazin-2-ones 393 upon treatment with lithium hexamethyldisilazide (LiHMDS) (Equation 42) <20010L3177>. 

By comparison, the lithium enolate of p-(phenylsulfonyl)isobutyrophenone (SIBP) was found mainly dimeric in THF, in equilibrium with its very reactive monomer (K, = 5 x 104 M-1)254. In the presence of lithium bromide, this dimer gave birth to a well-characterized 1 1 LiSIBP-LiBr mixed aggregate255. Similarly, a 1 1 LiSIBP-LiHMDS was demonstrated upon addition of lithium hexamethyldisilazide (Scheme 63)256. 

Zi,lsiV]-Lithium hexamethyldisilazide ( 6/i,IS/V]-LiI IMDS) coordination by 1,4,7-trimethyl azononane 9, along with other polyamines and polyethers, was studied by 6Li, 1SN, and 13C NMR spectroscopy <1996JA10707>. Samples of 1 ]-Ial IM1 JS with l-10equiv of 9 display exclusively 6Li doublets and 1SN triplets characteristic of solvated monomers. The low-temperature 13C NMR spectra recorded for the monomer complex of [6Li,15N]-LiHMDS... 

The dibenzo derivative of a cyclic acetylenic silane 96 was synthesized by mono-deprotonation of 1,2-diethynyl-benzene with 1 equiv of lithium hexamethyldisilazide (LiHMDS) followed by treatment with 0.5equiv of dichlor-odiphenylsilane (formation of 95). A repeat of the deprotonation step, followed by silylation cycle, gave 96 in 77% yield after column chromatography (Scheme 19). One-step preparation of 96 using 2 equiv of base and 2 equiv of the silylation agent also yielded the desired product, however, the yield was 50% of those of the previous method... 

Only one equivalent of base is required for the trifluoroacetylation step apparently the chelated tetrahedral intermediate is stable at -78°C and the ft-dicarbonyl product is not generated until workup. Crucial to the success of the trifluoroacetylation reaction in some cases is the selection of lithium hexamethyldisilazide (LiHMDS) for the generation of the ketone enolate under otherwise identical conditions diazo transfer to several aryl ketones proceeds in dramatically reduced yield when lithium diisopropylamide is employed as base. 

Treatment of a,/ -unsaturated lactam 252 with lithium hexamethyldisilazide (LiHMDS) followed by oxidation of the resulted dienolate with A -sulfonyloxaziridine 33 gave rise to the a-hydroxylated product 253 in 38% yield <2001TL7879>. The y-hydroxy product 354 was also isolated in 35% yield. 

Cbz Cp DABCO DBU DDQ (DHQD)2CLB (DHQD)2PYR DMF DME DMPU DMSO Et Fmoc HMPA ia KHMDS LDA LiHMDS Me MEM Ms NaHMDS Ph Piv PMB Pr Py (saltmen)Mn(N) benzyloxy carbonyl p 5 -cyclopentadienyl l,4-diazabicyclo[2.2.2]octane l,8-diazabicyclo[5.4.0]undec-7-ene 2,3 -dichloro-5,6-dicyanobenzoquinone dihydroquinidinyl p-chlorobenzoale (see Chart 1) dihydroquinidinyl pyrimidine (see Chart 1) dimethylformamide dimethoxyethane l,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone dimethylsulfoxide ethyl 9-fluorenylmethoxy carbonyl hexamethylphosphoric triamide inverse addition potassium hexamethyldisilazide lithium diisopropylamide lithium hexamethyldisilazide methyl (2-methoxy ethoxy )methyl methanesulfonyl sodium hexamethyldisilazide phenyl pivaloyl p -methoxy benzyl propyl pyridine nitrido[A,A/-(l,l,2,2-tetramethyl) bis(salicylideneaminato)]manganese (see Chart 1)... 

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