Stability lithium carbenoids

The question of configurational stability has been investigated first for vinylidene carbenoids and, more recently, for alkylcarbenoids. Vinyl anions are usually considered to be configurationally stable" ° the calculated inversion barrier of the ethenyl anion 10 (R = H) is about 35 kcal mol (equation 4)" . Concerning lithioalkenes, this configurational stability has been confirmed experimentally for a-hydrogen, a-alkyl and a-aryl substituted derivatives . The inversion of vinylidene lithium carbenoids was already... 

SCHEME 7. Test of the configurational stability of alkyl hthium carbenoids (a) fast equilibrium between enantiomeric lithium carbenoids (b) configurational stable hthium carbenoid 13... 

Configurational stability has also been confirmed for various metalated carbamates by Hoppe and coworkers. Remarkably, carbamate-protected alcohols such as 20 are deprotonated enantioselectively, when treated with i-butyllithium in the presence of (—)-sparteine. The lithium carbenoids like 21 (R = alkyl) thus generated turn out to retain their configuration (equation 11). Similar results have been obtained for a-lithiated amines and carbamate protected amines " . As a rule, dipole stabilization of the organolithium compounds in general also enhances the configurational stability of a-oxygen-substituted lithium carbenoids. 

A later modification of the original KObrich procedure entails the generadon of carbenoids in the presence of an added equivalent of lithium bromide salt (equadon 22). Appaiendy, the Lewis acid character of the added s t helps to stabilize the carbenoid by coordination widi the hdogen atom. The lithium salt is also implicated in Lewis acid complexation to the oxygen atom of the C=0 bond, and seems to assist in the cyclization step as well. 

The chelate formation in lithium complexes 17 or 20 contributes to stabilization. Enhancement of kinetic acidity arises from the formation of pre-complexes 16 and 19, respectively. Here, already a dipole is induced and, in addition, proton exchange can proceed intramolecularly via a five- or six-membered ring. Despite these favourable features, the acidity of alkyl carbamates 15 is lower than those of the 1-proton in butane n-BuLi does not lead to deprotonation. In order to suppress carbonyl attack, a branched amino residue NR2 such as diisopropylamino (in Cb) or 2,2,4,4-tetramethyl-l,3-oxazolidin-3-yl (in Cby) is essential. A study on the carbenoid nature of compounds 17 was undertaken by Boche and coworkers. ... 

Hammerschmidt, F. Hanninger, A. Enantioselective deproto nation of benzyl phosphates by homochiral lithium amide bases. Configurational stability of benzyl carbanions with a dialkoxyphosphoryloxy substituent and their rearrangement to optically active a-hydroxy phosphonates. Chem. Ber. 1995, 328, 823-830. Avolio, S. Malan, C. Marek, I. Knochel, P. Preparation and reactions of functionalized magnesium carbenoids. Synlett 1999, 1820-1822. 

Reactions of halogen-stabilized carbenoids with imines have been carried out using preformed lithium species e.g. equation or via a carbenoid generated from diiodomethane utilizing zinc-copper... 

Reactions of halogen-stabilized carbenoids with imines have been carried out using prefoimed lithium species (e.g. equation 36), or via a carbenoid generated from diiodomethane utilizing zinc-copper couple (Simmons-Smith conditions). A stereospecific ring closure is observed after the addition of lithiodichloromethane to a benzaldimine (equation 37).The addition of lithiochloro(phenylsulfon-yl)methane to aromatic imines affords 2-phenylsulfonyl-substituted aziridines, which can be deproton-ated and alkylated in excellent yield (Scheme 20). 

Organolithiums bearing a halogen on the a-carbon are termed carbenoids. Bromine and chlorine are sufficiently acidifying to allow preparation of the halocarbenoids, but fluorine requires additional stabilization, for example by phosphorus (yide supra). Lithium halocarbenoids are thermally unstable species whose chemistry must be performed at low temperatures and this feature has hindered their use in preparative synthetic organic chemistry. 

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