Aldimines imine anions from

Interestingly, the discovery of imine anions as potentially useful synthetic intermediates was made serendipitously by Wittig approximately 30 years ago. Acting upon an earlier discovery that lithium diethylamide may serve as a hydride donor to benzyne, Wittig examined the reaction of lithium diethylamide with benzophenone to ascertain whether the latter might also serve as a hydride acceptor. Surprisingly, the products observed from this reaction were benzhydrol (7) and the p-hydroxy aldimine (8) rather than the expected oxidation product (9). The sequence of reactions depicted in Scheme 2 was then proposed to account for this unexpected transformation. The initially produced aldimine (9) undergoes deprotonation with a second equivalent of lithium diethylamide to provide the imine anion (10),... 

Reactions of Imine Anions Derived from Aldimines... 

Anions derived from the aldimine of tiglaldehyde (14) react with carbonyl compounds preferentially at the a-position under conditions of kinetic control to give adducts (15), but products (16) derived from 7-attack are obtained under equilibrating conditions (Scheme 4). Addition of HMPA to the reaction or adduct mixture is required to promote isomerization of the initially formed a-adduct to the 7-product. There is also an increasing preference for 7-capture of the unsaturated imine anion as the degree of substitution a to the carbonyl function increases as in a-branched aldehydes and ketones (Table 2). Efforts to isomerize the initial a-adduct formed from reaction of the aldimine derived from crotonaldehyde with cyclohexanecarbaldehyde gave complicated mixtures. 

Reactions of Imine Anions Derived from Aldimines Following this exciting discovery Wittig, and subsequently others, then explored the scope and... 

Variants of TosMIC and imines have also been utilized for imidazole synthesis. For example, benzotriazol-1-ylmethyl isocyanide (BetMIC), 1320, reacts with aldimines 1321, like TosMIC, to form imidazoles 1322. In this case, the benzotriazolyl group stabilizes the anion formed in the first step and is spontaneously eliminated from the intermediate imidazoline. BetMIC derivatives are found to be unstable in the presence of strong bases such as LDA, -BuLi, and NaH. The most effective conditions for all of these reactions are found to be potassium /i t/-butoxide in DMSO or THF (Scheme 337) <1997H(44)67>. 

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). 

Table I, examination of which provides ample support for the generality of the process. It is noteworthy that increased branching at the carbon a to the imine function leads to decreased yields of the desired adducts (12) the reason for this failure has not been addressed, but reversion by retroaldolization is one likely possibility. The base that was typically employed to effect the deprotonation of the intermediate aldimines was lithium diisopropylamide, since alkyllithiums were found to add to the carbon-nitrogen double bond of the aldimines. Wittig observed in a number of instances that the overall yields of a,3-un-saturated carbonyl compounds obtained according to this procedure were better than by the corresponding classical Wittig reaction. Interestingly, the anion derived from the r-butylimine of isobutyraldehyde reacts with selected a,3-unsaturated ketones to give 1,4-adducts, whereas the corresponding hydrazone anions add to such ketones to provide the 1,2-adducts. ...

The asymmetric syntheses of 2-alkylcyclohexanones can be effected by the alkylation of the anions of chiral imines of cyclohexanones, prepared from either chiral a-amino-acid esters or chiral polymer-bound amines. Similarly, anions of chiral phenylethyl aldimines are alkylated to give an asymmetric aldehyde synthesis. ... 

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