Lithium aldimines

The addition of lithium and Grignard reagents to isocyanides which do not contain a-hydrogens proceeds by an a-addition to produce a metalloaldimine (7, an acyl anion equivalent). The lithium aldimines are versatile reagents which can be used as precursors for the preparation of aldehydes, ketones, a-hy-droxy ketones, a-keto acids, a- and 3-hydroxy acids, silyl ketones and a-amino acids (Scheme 5). - ... 

Lithium aldimine (131), an acyl anion equivalent derived from an isocyanide and an organolithium reagent, adds to aldehydes giving, after quenching with water, a-amino ketones (134) via the Amadori rearrangement (Scheme 33)." The a-amino ketone (134) results from a double tautomerization of a-hydroxy imine (132), formed initially after quenching with water. Thus, the imine (132) isomerizes to enolamine (133), which in turn tautomerizes to the observed product (134). 

Nitriles ketones. In a further study of synthetic uses of lithium aldimines (3, 279-280), Periasamy and Walborsky noted that f-butylnitrile is obtained in 88% yield by addition of f-butyllithium to trityl isocyanide. However, use of most lithium reagents results in formation of ketones (see below). The authors... 

Dilithium tetrachlorocuprate is recommended as an additive for cross coupling of Grignard compounds with tosylates even allylic and benzylic acetates give good yields . a-Methylene-ketones, -carboxylic acids and -lactones have been prepared via sulfides and sulfoxides. A convenient and general synthesis of acetylene derivatives from boranes via the reaction of iodine with lithium 1-alkynyltriorganoborates has been published ar-Nitrostyrenes can be easily obtained by a Wittig synthesis with formaldehyde in an aqueous medium . A new synthesis of unsym. ketones by reaction of dialkyldiloroboranes with lithium aldimines has recently been published . Metallo aldimines have also served for the synthesis of a variety of other compound classes such as a-hydroxyketones, a-keto acids, nitriles, and for the asym. synthesis of a-amino acids . Polycondensations of malononitriles with benzylic chlorides have been carried out quantitatively under mild conditions in dimethyl sulfoxide with triethylamine as acid acceptor . Carbonyl compounds can react with dibromoacetonitrile to yield a-bromo esters with additional carbon atom . ... 

Yamamoto, Y, Kondo, K., Moritani, I. 1974. Reaction of diaUcylchloroboranes with lithium aldimines. New method for synthesis of unsymmetrical ketones via organoboranes. Tetrahedron Lett. 15 793-796. 

In general the reaction of an aldehyde with a ketone is synthetically useful. Even if both reactants can form an enol, the a-carbon of the ketone usually adds to the carbonyl group of the aldehyde. The opposite case—the addition of the a-carbon of an aldehyde to the carbonyl group of a ketone—can be achieved by the directed aldol reaction The general procedure is to convert one reactant into a preformed enol derivative or a related species, prior to the intended aldol reaction. For instance, an aldehyde may be converted into an aldimine 7, which can be deprotonated by lithium diisopropylamide (EDA) and then add to the carbonyl group of a ketone ... 

Isocyanides that do not contain an a hydrogen react with alkyllithium compounds, as well as with Grignard reagents, to give lithium (or magnesium) aldimines. These metalated aldimines are versatile nucleophiles and react with various substrates as follows ... 

P-Lactams. In the presence of (CH3)2A1C1, lithium ester enolates react with enolizable aldimines to afford p-lactams in 60-95% yield as a mixture of cis- and trans-isomers. ... 

Synthesis of these prolylamide mimics is based on the Peterson olefination between tert-butyl a-fluoro-a-trimethylsilyl acetate and a protected hydroxypentanone. Further introduction of the amino group is rather difficult. This step has been accomplished through conversion of the ester into aldehyde, followed by the formation of the silylated aldimine with LiHMDS, and then the addition of methyl lithium (Figure 7.23). ... 

The cycloaddition of the /V-2-methoxvphenvI aldimines with lithium ynolates (for a review see [134]) has been reported to give (3-lactams enolates, that... 

Functionalization of tiglaldehyde. Anions of a,/5-unsaturated aldimines are known to react with electrophiles at both the a- and y-position. Thus, the lithium salt (1) of tiglaldehyde cyclohexylimine reacts with aldehydes to give, after acid hydrolysis of the imine, mainly the product of a-substitution. Addition of HMPT (1 equiv.) to the reaction followed by equilibration at 0° (2 hours) results mainly in formation of the product of y-subsitution. 

Aldimines can be trifluoromethylated at the imine carbon using Me3SiCF3 in dimethyl formamide at —20 °C, using a lithium carboxylate as catalyst.71 It is proposed that the carbon-silicon bond of the reagent is activated via formation of a lithium silicate bearing carboxylate and DMF ligands on silicon. A similar process has been used for diastereoselective addition to sulftnylimims.12... 

The reductive-trimethylsilylation of imines by means of granulated lithium in THF at 0-5 °C is a good method to synthesize ASMA and RSMA. This process was applied to aldimines and ketimines, lower yields being obtained in the latter case.190... 

C with LDA results in the chemoselective formation of an aza-enolate D, as in the case of the analogous aldimine A of Figure 10.30. The C=C double bond of the aza-enolate D is fnms-configured. This selectivity is reminiscent of the. E-preference in the deprotonation of sterically unhindered aliphatic ketones to ketone enolates (Section 10.1.2, paragraph Stereocontrol in the Formation of Lithium Enolates ) and, in fact, the origin is the same both deprotonations occur via six-membered ring transition states with chair conformations. The transition state structure with the least steric interactions is preferred in both cases, which is the one that features the C atom in the /3 position of the C,H acid in the pseudoequatorial orientation. 

Asymmetric versions of this fundamental way of making carbon-carbon bonds have attracted considerable attention lately. The diastereoselective version has proven successful in terms of high inductions and versatility of the substrate (unsaturated ketones, esters, amides, sultames, oxazolidines, aldimines. ..). The very large amount of data reported in this area precludes its coverage but excellent reviews are available143-145. The fine example displayed below, in which the intermediate enolate is trapped intramolecu-larly, illustrates the potency of this approach (Scheme 31)146. Similarly, good results were obtained with lithium enolates derived from (—)-8-phenylmenthyl esters147. 

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