1- methylpropane lithium

The lithium-TMEDA complex 1, obtained by deprotonation of (S)-(E)-1 -methyl-2-butenyl diisopropylcarbamate (84% ee), affords, after metal exchange by tetraisopropoxytitanium and addition to 2-methylpropanal, the homoaldol adduct ( + )-4 with 73% ee, whereas (-)-4 (53 % ee) is obtained when chlorotris(diethylamino)titanium is used104. 

The reagents prepared by lithiation (see Section 1.3.3.3.1.2.) and titanium exchange of (S)-(Z)-l-methyl-2-butenyl diisopropylcarbamate106 show a diminished reactivity when compared with those derived from the ( -isomer, indicating that in both metalation steps the doublebond geometry is retained16. After treatment of the lithium -TMEDA complex with chlorotris-(diethylamino)titanium and 2-methylpropanal, the homoaldol adduct (3S,47f)-(Z)-4-hydroxy-1,3,5-trimethyl-l-hexenyl diisopropylcarbamate [( + )-4], is formed with 88% ee16. 

The combination of the enantiomerically pure 7V-methylephedrine derived silylketene acetal l-[(l/ ,2S)-2-dimethylamino-1-phenylpropoxy]-l-triniethylsilyloxy-l-propene with the chiral aldehyde (,R)-3-benzyloxy-2-methylpropanal leads, after reduction with lithium aluminum hydride, to the formation of a single 1,3-pentanediol 9 ( matched pair ). 

Tertiary and aromatic nitroso compounds react with aryl Grignard or aryl-lithium reagents giving the corresponding hydroxylamines . This reaction is useful for preparation of alkyl- and aiylhydroxylamines (e.g. 109, equation 80 and 110, equation 81) and can be considered as complementary to arylation of hydroxy lamines with activated aryl halides. It has been used for functionalization of cyclophanes with the hydroxy amino group. The main limitation of the reaction is the relatively restricted choice of available aliphatic nitroso components, so most of reactions were done with 2-nitroso-2-methylpropane. There is no literature data about the possibility of removal of the tert-butyl group from these compounds. 

A more general and efficient approach to alkynyl carboxylates, also thought to involve alkynyliodonium carboxylate intermediates, entails the treatment of bis(acyloxyiodo)-arenes with alkynyllithium reagents (equation 88)81. These reactions are best conducted in the presence of 2-nitroso-2-methylpropane in order to suppress oxidative coupling of the lithium acetylides by the acyloxyiodanes. 

The phosphorus-carbon bond of triphenylphosphine is easily cleaved by lithium in THF (tetrahydrofuran) at room temperature. The phenyllithium which is also formed in this reaction is destroyed in situ by allowing it to react with 2-chloro-2-methylpropane. Isobutylene gas is given off and the diphenylphosphide ion is then allowed to react with chlorotrimethylsilane. The product, diphenyl(trimethylsilyl)phosphine, is formed in 80% yield. The diphenylphosphide ion is usually formed in 85-95% yield, based on the lithium consumed. 

The partial reduction of arenes can be achieved using the Birch reduction An alkali metal (lithium, sodium or potassium) is dissolved in liquid ammonia in the presence of the arene, an alcohol, such as 2-methylpropan-2-ol tert-buty alcohol) and a co-solvent to assist solubility. 

Stereoselective Aldol Reactions. The (R)- and (S)-2-hydroxy-1,2,2-triphenylethyl acetates (HYTRA) offer a simple soludon for a stereoselecdve aldol addition of a-unsubstituted enolates. When a suspension of HYTRA is treated in THF with 2 equiv of Lithium Diisopropylamide, a clear soludon of the enolate forms (eq 1). Subsequent dilution with 2-methylbutane followed by the addition of 2-methylpropanal affords predominantly the (R,R)-diastereomeric adduct. Alkaline hydrolysis not only delivers (/ )-3-hydroxy-4-methylpentanoic acid in 86-94% ee but also liberates the optically pure auxiliary reagent (/ )-1,2,2-triphenylethane-1,2-diol, which can be removed and reused (eq 1). - ... 

Analogous reactions are used to manufacture sec-butyllithium and ferf-butyl-lithium using 2-chlorobutane (scc-butyl chloride) and 2 chloro-2-methylpropane (fert-butyl chloride), respectively, as shown in eq 4.13 and 4.14 ... 

In DMF containing lithium perchlorate, reduction of o -bromopropiophenone at mercury gives l,4-diphenyl-2,3-dimethylbutan-l,4-dione in 65% yield [236]. However, electrolysis of a-bromopropiophenone in the presence of benzoyl chloride affords only l,3-diphenyl-2-methylpropan-l,3-dione. Other studies involving reduction of phenacyl bromides include the electrosynthesis of 4-aryl-2-methylfurans [237] and the regioselective synthesis of enol carbonates [238] semicarbazones of phenacyl bromide can be converted into 3,7-diaryl-2/7-imidazo[2,l-Z>][l,3,4]oxadiazines [239]. Reduction of 1,2-dibenzoyl-chloroethane at mercury in DMF containing lithium perchlorate affords mixtures of phenyl tribenzoyl cyclopentanols and diphenyl dibenzoyl butanediones [240]. 

Partial demethylation occurred of the spiro cannabinoid compound illustrated by treatment in hexamethylphosphorictriamide with the lithium salt of 2-methylpropane-2-thiol in the same solvent at 70 C during 2 hours to give an 89% yield of (+)-dehydrocannabispiran. The lithium salt was prepared from lithium hydride and the thiol in oxygen-free hexamethylphosphoric triamide by reaction at 50 C during 5 hours (ref.149). 

Methyl ethers of methyl 6-alkylsalicylates (R = n-alkyl) were smoothly demethylated by treatment with excess lithium 2-methylpropane-2-thiolate (prepared from t-butyl thiol and n-butyllithium) in dimethylformamide at ambient temperature during 1 hour to give the ester. This was hydrolysed by heating the mixture under reflux (ref. 150). The method has applicability to alkyl dimethylorsellinates. 

When lithium picolyl reacts with acetic anhydride, there is formed a mixture of a,y-(bis-2-pyridyl)- -methylpropan-/3-ol and a-(2-pyridyl)-propan- 8-one. The latter on hydrogenation in acetic acid solution over platinum gives rise to dZ-isopelletierine (499). 

Lithium aluminum hydride reduction of l,2-epoxy-2-methylpropane gives, as expected, predominantly tert-butyl alcohol. 

As applied to an amino acid synthesis, the ester enolate must react with another molecule that contains a nitrogen moiety. In one example, methyl 2-methylpropan-oate was treated with lithium diisopropylamide and then with 4-bromobutanenitrile to give 4.68. Catalytic hydrogenation of the cyano group gave methyl 6-amino-2,2-dimethylhexanoate (4.dP).35a in this case, the nitrile was the amine surrogate and the ester was the acid precursor. 

The isolation of the non-cyclic amino(aryl)carbenes and amino(alk-yl)carbenes demonstrated that singlet carbene centres can be sufficiently stabilized by only one a-nitrogen atom. In 2005, Bertrand and co-workers succeeded in preparing the first cyclic alkyl(amino)carbenes (CAACs Scheme 1.15). The precursor for CAAC 108 was obtained from an imine by deprotonation with LDA (LDA = lithium diisopropylamide) and subsequent reaction with 1,2-epoxy-2-methylpropane to give 106, which was converted into cyclic aldiminium salt 107 by reaction with trifluoromethanesulfonic acid... 

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