Lithium cyclohexylisopropylamide

Lithium cyclohexylisopropylamide Lithium diisopropylamide Lithium hexamethyl disilazide Lithium 2,2,6,6-tetramethylpiperidide Methylaluminum I ij-(4-bromo-2,6-di-tert-butylphenoxide) I (s-(2,6-di-t-butyl-4-methylphenoxy)methyl aluminum mefa-Chloroperoxybenzoic acid Methyl... 

The first successful preparation of lithium ethyl acetate was using the base lithium hexam-ethyldisilazanide12,14 at — 78 CC in tetrahydrofuran. The much greater stability of the lithium salt as compared to the previously prepared13 sodium ethyl acetate was noted and used in the reaction with carbonyl compounds12. The attack of alkyl halides as electrophiles on the lithium salts of esters, prepared by the action of lithium cyclohexylisopropylamide on the esters at low temperatures in tetrahydrofuran, furnished the a-alkylated products in yields of 50 -90%16,17. 

The carbamate ester derivatives of 2,3-bornanediol 11 and 12 were alkylated by treatment with lithium cyclohexylisopropylamide in tetrahydrofuran at —8013 C and subsequent addition of hexadecyl iodide or iodomethane. respectively, in the presence of HMPA. Chemical yields were 90% and the diastereomeric ratios 13a/13b were 93 7 and 10 90, respectively117. 

Alkylation of the simplest 7-lactone, butyrolactone (5), has been described by the use of lithium cyclohexylisopropylamide and iodomethane or an alkyl bromide10. In this paper the low temperature ( — 78 °C) was explicitly recommended in order to avoid self-condensation. It was noted that more than one equivalent of base increased the yield. 

Deprotonation of either the (4S.5R)- or (4/ ,5S)-enantiomer of 3-acyl-1,5-dimelhyl-4-phenyl-2-imidazolidinones 4 by lithium cyclohexylisopropylamide (LICA)1 or diisopropylamide2 furnishes chiral, supposedly chelated enolates, very similar to those enolates obtained from 2-oxazolidi-nones (see Section 1.1.1.3.3.4.2.1.). With LICA the. yyn-enolate is formed exclusively, as shown by O-silylation of the enolate with /ert-butylchlorodimethylsilane1. Attack of an electrophile, such as a haloalkane, from the less hindered side furnishes products (usually crystalline) with a moderate to high degree of diastereoselectivity (see Tabled)1 2. The diastereoselectivities observed in comparable alkylation reactions of the 3-acyl-4-cyclohexyl-l,5-dimethylimidazo-lidinone 3b are superior to those obtained with the 4-phenyl derivative 3a2,7. Thus, as also observed in similar alkylations with oxazolidinones10 (see Section 1.1.1.3.3.4.2.1), a phenyl substituent on the chiral auxiliary seems to be relatively inefficient as a steric control element. 

Asymmetric alkylation of esters. HMPT tias a marked influence on the asymmetric alkylation of enolates of chiral esters, such as the propionates 1, where R is a derivative of (+ )-camphor. A typical example is shown in equation (I). The esters are deprotonated with lithium cyclohexylisopropylamide (LICA) cither in THE (A) or in THF/HMPT (B). In the first case, alkylation with benzyl bromide results mainly in (2S)-2 in the second case, formation of (2R)-2 is markedly favored The effect of HMPT is considered to result, at least in part, from preferential formation of the (E)-enolate of 1. 

Hoye and co-workers (ref. 92) later reported the total synthesis of ancistrobrevine B (228), isolated from Ancistrocladus abbreviatus (ref. 93) and korupensamine C (229), isolated from Ancistrocladus korupensis. The approach to these natural products also utilised a benzyne cycloaddition to construct the naphthalene moiety. Thus, treatment of the amide 222 and bromide 230 with lithium cyclohexylisopropylamide furnished naphthalene 231 in low yield (Scheme 30). 

Hexamethylphosphoramide (Me3N)3P=0 Hexamethylphorous triamide (Me3N)3P Isopropyl — CH(CH3)2 Lithium cyclohexylisopropylamide Lithium diisopropylamide LiN(iPr)2 Lithium hexamethyl disilazide LiN(SiMe3)2 Lithium 2,2,6,6-tetramethylpiperidide meta-Chloroperoxybenzoic acid Methyl — CH3... 

Reagents i, MeC"CLi, then UAIH4, NaOMe ii, MeMgBr, then (PrC0)20 iii, Lithium cyclohexylisopropylamide, THF... 

Lithium cyclohexylisopropylamide Lithium diisopropylamide Lithium hexamethyidisilazide Lithium 2,2,6.6-tetrametbylpiperidide Methylaluminum bt.t-(4-bromo-2,6-di-[Pg.5]

The products arising from the base-catalysed cyclization of 2-(prop-2-ynyI-oxy)-benzamides (322) are dependent on the base employed.For example, the primary amide (322 R = H), with sodium methylsulphinyl methylide in DMSO, yields a mixture of oxazepinones (323) (34%) and (324) (7%), whereas lithium cyclohexylisopropylamide affords oxazepinone (323) exclusively, and sodium... 

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