Lithium di-isopropylamide

Finally, it has been shown that methoxyselenylation of conjugated dienes followed by treatment with lithium di-isopropylamide can be a convenient method for the preparation of 1-phenylseleno-l,3-dienes and their methyl-substituted homologues 134 (equation 126)138. 

Treatment of 2,2,6-trimethylcyclohexanone with lithium di-isopropylamide (LDA) followed by phenyltriflimide (Af-phenylbis (trifluoromethanesulphonimide) gave the corresponding triflate [24]. The... 

Via an amidoalkylation of bis(trimethylsilyl)ethyne (12) with methyl 2-chloro-N-ethoxycarbonylglycinate (57) under the influence of aluminum chloride the corresponding N-(ethoxycarbonyl)-a,a-TMS-ethynyl-glycinate (55) is isolated which is converted by means of lithium-di-isopropylamide (LDA) into a carbanion that reacts with alkylhalide to the substituted glycinate 59. Finally, after alkaline hydrolysis the unprotected a-acetylenic-a-aminoacid (60) (e. g. R = Benzyl a-ethynyl-a-phenyl-alanine is then obtained (Scheme 7). 

The direction of the base induced ring opening of oxaspiropentanes proved to be highly depending on the nature of the base and solvent. Thus the epoxide 100 opened either mainly to l-(l-cyclopropenyl) cyclohexanol 106 on reaction with lithium di-isopropylamide in ether or mainly to the expected l-(l-cyclohexenyl) cyclopropanol 105 on reaction with lithium diethylamide in pentane, Eq. (31)57). 

It is noteworthy that preferential formation of the less substitued enolate is also observed when ketones are treated by very strong bases in aprotic solvents, i.e., when the kinetic enolates are formed e.g., a ratio of 85 15 between [45] and [46] was observed when methyl propyl ketone [44] was ionised by lithium di-isopropylamide in dimethyl ether (House et al., 1971)1. 

Enolates may be converted directly into a-hydroxy-ketones by reaction with the molybdenum peroxide complex MoOs,py,HMPA. The 17-ketone (188), transformed into its enolate with lithium di-isopropylamide at —70°C, gives the 16a-hydroxy-17-ketone (189) in 75% yield.172 Carbonyl transposition to the vicinal position can be effected in high yield by a new five-step process.173 A 17-oxo-steroid (188) was transformed into the 16-ketone (193) via the phenylthioketone (190) and the 16-phenylthio-16-ene (192) by the route illustrated in Scheme 5. 

Methylcyclopropene has also been prepared by reacting 3-chloro- or bromo-2-methylpropene with sodium amide or lithium di-isopropylamide in mineral oil and the product trapped in an a-dextrin matrix (3). In addition, it has been prepared in mineral oil using catalytic amounts of hexamethyldisilazane (4) as described below ... 

Lithium di-isopropylamide (2.3 eq) was added to the product from Step 4 dissolved in 12 ml diethyl ether at 0°C. After the mixture was stirred 2 hours, bis(phenylsulfonyl) sulfide (0.089 mmol) was added at -78 °C and the mixture kept at this temperature 3 hours. Over a period of 12 hours the mixture slowly warmed to ambient temperature. Thereafter, it was purified as in Step 1 but using hexane/chloroform, 10 1, and the product isolated in 47% yield, mp = 311-325.5°C. H- and C-NMR and MS data provided. 

Hwu and co-workers reported selective cleavage of a benzyl (Bn) ether with lithium di-isopropylamide (LDA) in the presence of a methoxy group however, by using sodium bis(trimethylsilyl)amide [NaN(SiMe3)2], the dimethoxybenzene undergoes selectively mono-O-demethylation (Scheme 1.21). 

An unsymmetrical ketone can form two different enolates. In some situations it is possible to distinguish between them by trapping the separate enolates as their silyl enol ethers. The anions may then be regenerated from the silyl enol ether in an aprotic solvent under non-equilibrating conditions using fluoride ion. The rapidly formed kinetic enol of 2-methylcyclohexanone may be trapped using lithium di-isopropylamide as the base (Scheme 3.77a). On the other hand, the thermodynamically more stable enol is trapped with a milder base such as triethylamine (Scheme 3.77b). ... 

Diaryl-l,2,4,5-tetrazines, when treated with bulky amides such as lithium di-isopropylamide, undergo two competing reactions. In the first, tetrazine is reduced with concomitant formation of an imine from the amide. The imine is then attacked further by amide to give a pyridazine. For example, 3,6-diphenyl-l,2,4,5-tetrazine is converted with lithium diethylamide into 3,6-diphenylpyridazine in low yield. With lithium di-isopropylamide, 4-methyl-3,6-diphenylpyridazine is obtained in moderate yield [83JCS(P1)1601]. 

Preparative Method prepared by carboxylation of (R)-(+)-Methyl p-Tolyl Sulfoxide carbanion generated with Lithium Di-isopropylamide (eq 1). ... 

Syntheses of (2) and flOf were conveniently effected tScheme 4) starting from diethyl succinate (12) (28). The resultant dienolate (13). obtained by the action of two equivalent of lithium di-isopropylamide (29) gave on alkylation with methylenedioxybenzyl bromide in excellent yield a mixture of the ( )-ester (14) and meso-cster (15) which by alkaline hydrolysis yielded the dicarboxylic acid mixture (16) and (17). Without separation, this mixture on heating wih acetic anhydride gave the known /ron.r-dipiperonylsuccinic anhydride (18) (30). Reduction of (18) with lithium aluminium hydride gave ( )-dihydrocubebin Q), acetylation of which yielded ( )-ariensin (10). 

Lactone formation, by intramolecular condensation of a-acetoxy-ketones in strongly basic media, has been examined systematically. Lithium di-isopropylamide in ether is effective as the base conditions must be chosen according to the reactant. Scheme 8 illustrates successful reactions, which afforded either the /3-hydroxy-y-lactone or the butenolide, depending upon the ease of adoption of the conformation necessary for elimination of water. The method appears to be limited to tertiary a-acetoxy-ketones. 

The epoxides (120) can be metallated specifically with lithium di-isopropylamide (Scheme 20). ... 

Chloro- or 3-bromo-5-phenyl-X -phosphorins undergo nucleophilic substitution with lithium piperidide in piperidine to yield the 3-piperidino derivative. Similar results occur with lithium di-isopropylamide (Markl and Hock, ihid., p.5055). 

In this work the (i )-silyalkyne (125) was treated with lithium di-isopropylamide and methyl lithium and then the epoxide (126) was added. This gave the lactone (127) which with potassiiim hydroxide in ethanol produced the protected amino alcohol (128). Reaction of this compound with formalin afforded the cyclopentaoxazolidine (129) and this when heated with one molar equivalent of camphorsulphonic acid and chromatography yielded the indolizidine (130, R=Bn). Deprotection and oxidation under Swern conditions gave the aldehyde (131). Finally a Wittig reaction between this aldehyde and the ylide (132) produced the enone (133) which was reduced with lithium aluminium hydride to yield (+)-pumiliotoxin-B, together with a small amount (-6%) of its erythro-isomer (Scheme 6). 

Directed aldol condensation. Aldol condensation between an aldehyde and a ketone usually is not successful because self-addition of the aldehyde is the preferred reaction. Wittig and Reiff,1 however, showed that, if the aldehyde is first converted into a Schiff base (cyclohexylamine was used) and then metalated with lithium di-isopropylamide (chosen for obvious stcric reasons), aldol condensation can be achieved, usually in good yield.2 In the case of ketones, this route is superior to olefination via a phosphorylide. 

The synthesis of 10,14-dimethylretinal (104) isomers has been described. Successive chain lengthening of jS-ionone (108) by reaction with propylidene-cyclohexylamine in the presence of lithium di-isopropylamide, followed by... 

Reagents i, lithium di-isopropylamide ii, Me Bu SiCl iii, singlet oxygen. 

In a new procedure, several 3-substituted diazepam derivatives (124) have been prepared, in moderate to good yields, by allowing metallated diazepams (123) to react with alkyl iodides, carbonyl compounds, or esters. Two equivalents of lithium di-isopropylamide (LDA) were required to produce an equilibrium concentration of (123) that was sufficiently high for synthetic use. ... 

Rearrangement of triphenylphosphate in tetrahydrofuran, added to lithium di-isopropylamide in the same solvent at -78°C under nitrogen followed by further reaction during 4 hours has been reported to afford tri-(2-hydroxyphenyl)phosphine oxide in 87% yield (ref.48). 

Removai of the methoxy group and its substitution by cyanomethyl in the protected estrone derivative shown in the form of the arene chromium tricarbonyl complex in tetrahydrofuran solution, was achieved in 46% yield by treatment at -78 C with lithioacetonitrile (from acetonitrile in tetrahydrofuran containing hexamethylphosphorictriamide and lithium di-isopropylamide at -78°C) followed by stirring for 4 hours at ambient temperature (ref. 104). 

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