Alkyllithium- -sparteine complexes

The addition of alkyllithium-(—)-sparteine complexes to C=C bonds can lead to chiral carbanions and may be an interesting alternative to deprotonation. 

W-Substituted 2,4-alkadien-l-ols such as 474 add the alkyllithium/(—)-sparteine complex preferentially to the 2-position to form via the alkoxide the corresponding allyllithium intermediates 475 . Protic workup leads to a mixture of ii/Z-alkenols 476 and 477 on catalytic hydrogenation the -branched alcohols 478 are isolated (equation 130). 

Equilibration of Configurationally Labile Organo-lithium Reagents. The equilibration of diastereomeric pairs of alkyllithium-(—)-sparteine complexes and trapping by achiral electrophiles gives enantioenriched products. Examples are a-(A/,JV-diisopropylcarbamoyloxy)benzyllithium in ether, not in THF, l-phenylethyllithium, and the dilithium salt of A/-methyl-3-phenylpropanoic acid amide (eq 2). ... 

By careful optimization, Widdowson and coworkers were able to show that methoxy-methyl ethers of phenols are better substrates for alkyllithium-diamine controlled enan-tioselective deprotonation, and (—)-sparteine 362 is then also the best ligand among those surveyed the BuLi-(—)-sparteine complex deprotonates 447 to give, after electrophilic quench, compounds such as 449 in 58% yield and 92% ee (Scheme 180) . Deprotonation of the anisole complex 410 (see Scheme 169) under these conditions gave products of opposite absolute stereochemistry with poor ee. 

In order to avoid polymerization and to achieve better stereocontrol by quasi-intramolecular addition, a carbanion-stabilizing group and a complexing substituent for capturing alkyllithium/(—)-sparteine in the substrate are useful. This carbolithiation protocol was realized with great success by Marek, Normant and coworkers (equation 125) Addition of n-BuLi/(—)-sparteine (11) onto the lithium alcoholate derived from ( )-cinnamyl alcohol (457) in cumene at 0°C afforded the addition product with 82% yield and 80% ee. 

Physical Data bp 137-138°C/1 mm Hg d 1.02gcm [a]p° — 17.5° (c=2, EtOH). X-Ray structures of several complexes of metal salts, alkyllithium derivatives, and of allylpalladium and studies on the conformation in solution and a NMR study on the structure of the 2-propyllithium-ether-(—)-sparteine complex have been reported. 

The crucial reagents for the synthesis of the enantioemiched lithium compound (iS)-2 are (-)-sparteine complexes of simple alkyllithium bases. P. Beak and cowokers showed that f-BuLi and i-PrLi complexed by (-)-sparteine could be efficiently used for an asymmetric deprotonation reaction, whereas complexes of the chiral amine and t-BuLi or n-BuLi showed hardly any stereoselectivity or reactivity (Scheme 3) [2]. 

One of the earliest descriptions of an asymmetric lithiating reagent was reported by Nozaki and co-workers in 1968 (35). (—)-Sparteine was used to coordinate n-butyllithium, and this complex stereoselectively added to several carbonyl compounds (Reaction 32). Moreover, the Skattebol-Moore method (which consists of dehalogenating gem-dihalo-cyclopropanes with an alkyllithium complex) by Nozaki to synthesize allenes gave optically active products when the n-butyllithium/ ( —)-sparteine complex was used (36). 

In solution [7] and solid state (-)-sparteine-coordinated i-PrLi exists as an unsymmetric aggregate containing two lithium alkyls [5] this dissociates during the reaction under formation of a precoordinated complex. Apart from j-BuLi, j-PrLl is the only known simple alkyllithium compound which can, in combination with (-)-sparteine, efiSciently be used for asymmetric deprotonation of iV-Boc-pyrrolidine [2]. 

Alkyllithiums can be turned into chiral bases in quite a simple way—by complexation with a chiral ligand. A widely used example is the tetracyclic diamine (-)-sparteine. Sparteine s structure looks complex, but it is a relatively widely available natural product which folds around the lithium atom of an alkylUthium and places the base in a chiral environment. 

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