Deprotonation lithium- -sparteine complexes

The lithium-(-)-sparteine complex, generated by deprotonation of 1-methylindene, does not lose its configuration in diethyl ether solution even at room temperature80 presumably, the observed major diastcreonier is the thermodynamically determined product. Substitution with carbonyl compounds leads to 1-substituted (fl)-l-methyl-l//-indenes with >95% ee in high yields81. 

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]. 

The rationale for the observed configuration (Scheme 3.29), is based on the X-ray structure of another a-carbamoyloxyorganolithium sparteine complex [185]. After deprotonation, the chelated supramolecular complex shown in the lower left is postulated. This structure contains an adamantane-like lithium-diamine chelate, and contains new stereocenters at the lithiated carbon and at lithium itself. Note that epimerization of the lithiated carbon would produce severe van der Waals repulsion between R and the lower piperidine ring, whereas epimerization at lithium produces a similarly unfavorable interaction between the same piperidine ring and the oxazolidine substituents. Thus, the carbamate is tailor-made for sparteine chelation of only one enantiomer of the a-carbamoyloxyorganolithium. These effects may provide thermodynamic stability to the illustrated isomer. To the extent these effects are felt in the transition state, they are also responsible for the stereoselectivity of the deprotonation. 

Both dimethylphenylphosphine-borane (107) and -sulfide (108) are enantio-selectively deprotonated by a lithiumalkyl (—)-sparteine complex as demonstrated by subsequent reaction with electrophiles to give products with e.e. values of 80-87% (Scheme 8). Oxidative coupling of (109) in the presence of copper(II) pivalate gives the (S. S)-isomer (110) as the major product. Asymmetric metalla-tion and silylation of diphenylphosphinyl ferrocene (111) using the chiral lithium amide base derived from di(l-methylbenzyl)amine has been reported to give an... 

The deprotonations are complete within a few hours at -78 °C and afford the lithium car-benoid sparteine complexes (5)-l-(-)-3 with excellent enantioselectivities. [6-12] Whereas sparteine complexes of lithiated secondary allyl and primary alkyl carbamates are configurationally stable below -30 °C, those of primary allyl carbamates such as 4 (-)-3 are not configurationally stable even at -70 °C. It is, however, possible to use these reagents in synthesis, since the preferential crystallization of the S diastereomer in pentane/cyclohexane drives the equilibrium completely to one side. After a low-temperature transmetalation of (5 )-4-(-)-3 with an excess of tetraisopropo-xytitanium, the allylic titanium reagent (Ji)-S is obtained with inversion of configuration. The addition of various aldehydes to (R)-5 furnishes homoaldol adducts of type 6 with... 

Kinetic resolution between diastereomeric (—)-sparteine-lithium complexes may also occur on a later step of a reaction sequence. Almost no stereodifferentiation between the enantiomers (R)- and (5)-116 takes place in the deprotonation of rac-116 (S,S)-117 and (7 ,5 )-117 are formed in essentially equal amounts (equation 26) . Only (R,S)-... 

The breakthrough was achieved by D. A. Evans and coworkers " , who demonstrated that aryldimethylphosphine-borane complexes 195 are easily deprotonated by i-BuLi/(—)-sparteine (11), furnishing efficient enantiotopic selection between the methyl groups (equation 45). The intermediate lithium compound 196 was added to benzophenone (to give alcohols 197) or oxidatively coupled to furnish bisphosphines 198 with high ee. The major amount of the minor diastereomer epi-196 is removed as separable meso- 9. ... 

According to Widdowson, [(methoxymethoxy)benzene]tricarbonylchromium (448) was deprotonated with enantiotopos differentiation by n-BuLi/(—)-sparteine (11), and the lithium intermediate 449 was trapped by various electrophiles to give the products 451 with ee values up to 97% (equation 122) . Surprisingly, opposite enantiomers are formed when stoichiometric or excess amounts of base are applied. The authors presume that in the dilithium intermediate 450 the C—Li bond (in the rear) has a higher reactivity than the other one (pointed to the front). The deprotonation procedure was also applied to a couple of 1,4-disubstituted chromium complexes . 

In the event that the alkylcarbamate contains further lithium-coordinating heteroatoms, enantioselective deprotonation becomes impossible because sparteine is displaced from the lithium in this reactive complex. So, for example, the A,A-dimethyIamine 424 (R = Me) is lithiated with only 10% ee, which its dibenzyl analogue is lithiated in 97% ee.162 Most oxygen-containing functional groups do not have this effect.178181... 

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]. 

Since Evans et al. [78] has discovered that prochiral alkyl(dimefliyl) phosphine boranes can undergo the enantioselective deprotonation of one methyl group, using butyllithium and ( )-sparteine 141, these compounds have been widely used for the synthesis of P-chirogenic borane phosphines [79-105]. Lithium alkyls form chiral complexes 142 with sparteine 141 and related chiral diamines, which were investigated by single crystal X-ray analysis (Scheme 43) [82-87]. 

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