Butyllithium/ -Sparteine

It should be noted that the sense of asymmetric induction in the lithiation/ rearrangement of aziridines 274, 276, and 279 by treatment with s-butyllithium/ (-)-sparteine is opposite to that observed for the corresponding epoxides (i.e. removal of the proton occurs at the (S)-stereocenter) [102], If one accepts the proposed model to explain the selective abstraction of the proton at the (R) -stereo-center of an epoxide (Figure 5.1), then, from the large difference in steric bulk (and Lewis basicity) between an oxygen atom and a tosyl-protected nitrogen atom, it is obvious that this model cannot be applied to the analogous aziridines. 

An efficient kinetic resolution of racemic secondary allyl carbamates was accomplished by the jw-butyllithium-(-)-sparteine complex76 131. Whereas the R-enantiomer (80% ee) is recovered unchanged, the 5-enantiomer is deprotonated preferentially. 

Another result of great importance—the conformational asymmetric polymerization of triphenylmethyl methacrylate realized in Osaka (223, 364, 365)— has already been discussed in Sect. IV-C. The polymerization was carried out in the presence of the complex butyllithium-sparteine or butyllithium-6-ben-zylsparteine. The use of benzylsparteine as cocatalyst leads to a completely soluble low molecular weight polymer with optical activity [a]o around 340° its structure was ascertained by conversion into (optically inactive) isotactic poly(methyl methacrylate). To the best of my knowledge this is the first example of an asymmetric synthesis in which the chirality of the product derives finom hindered rotation around carbon-carbon single bonds. 

Geminal dibromocyclopropanes have been reduced by chromium(lI) - (-i-)-tartrate complex and by butyllithium - (+)-sparteine complex to give cyclic allenes and 1-phenyl-l,2-butadiene with very low enantioselectivity (< 1 % op)122. In addition, cyclic diallenes of unknown optical purity have been reported123, l24, e.g., 3,4,9,10-cyclododecatetraene-l,7-dione is prepared using a stoichiometric amount of methyllithium and a sixfold excess of (-)-sparteine123,124. 

The Sparteine Method 42 was applied successfully to generate chiral a-lithiated pyrrolidine when using the Boc-protected (tcrt-butoxycarbonyl)pyrrolidine and sec-butyllithium/sparteine as an asymmetric deprotonating agent in diethyl ether at — 78 °C. Alkylation, silylation, stanny-lation and methylation occurred with good yield (70-75%) and high selectivity (95% ee)53. 

Asymmetric deprotonation of /V-(/-butoxycarbonyl)indolincs at the 2-position with s-butyllithium-(—)-sparteine has been reported.161 Results of an ab initio MO study of deprotonated 2,3-dihydrooxepin suggest that the allylic anion is 15 kcal mol 1 more stable than the vinylic anion, which is, in turn, 8 kcal mol 1 more stable than the vinyl anion of cyclohepta-l,3,5-triene.162... 

Generation of Enantioenriched, Configurationally Stable Organolithium Reagents. (1 S,2E)-1 -(N.Af-Diisopropyl-carbamoyloxy)-l-methyl-2-butenyllithium-(—)-sparteine is configurationally stable in solution and is obtained by kinetic resolution of the racemic 2-alkenyl carbamate by n-butyllithium-(—)-sparteine with >80% de (eq 4). The enantioenriched allylstan-nane, obtained on y-stannylation, was used as chiral homoenolate reagent. The methoxycarbonylation (a, inversion) yields enantioenriched 3-alkenoates. ... 

Alkyl carbamates, derived from 2,2,4,4-tetramethyl-1,3-oxazo-lidine (R-CH2-OCby), are deprotonated by s-Butyllithium- —)-sparteine with differentiation between the enantiotopic protons (eq 5). The pro-S proton is removed with high stereoselectivity and reliability, and, subsequently, stereospecifically substituted by electrophiles with stereoretention to give enantiomerically enriched secondary alcohols (>95% ee) after deprotection, ... 

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). 

Once it was demonstrated that it adds stereoselectively, the n-butyllithium/ ( —) -sparteine complex was used to prepare a series of optically active ferrocenes (36). Treatment of isopropyl ferrocene with a 2.5-molar excess of the lithiating complex followed by reaction with an electrophile... 

Of considerable interest for synthetic applications are the deprotonations of alkyl carbamates RCHiOCbx or RCHaOCby with s butyllithium (-)-sparteine, followed by the alkylation with an electrophile. [7] Most electrophiles such as CO2, MesSnCl, MesSiCl, Mel, Me2CHCHO react with retention of configuration to afford protected alcohols of type 7 (Eq. 4). 

Efficient kinetic resolution was also observed in reactions of carbamates rac-75 and rac-80 by means of sec-butyllithium/(-)-sparteine (see also Eq. 25) [65, 66] Fig. 3 shows the more reactive enantiomer R)-75 and (S)-80, respectively the substitution products, arising from the abstraction of the pro-S proton were formed with >95% ee. PM3 calculations correlate well with the experimentally recorded - opposite - selectivities [66]. 

The deprotonation of the secondary carbamate rac-254 by -butyllithium/(-)-sparteine (diethyl ether/hexane, -78°C) is combined with an efficient kinetic resolution [Eq. (72)] [155,168]. The lithium compound (S)-256 is configuration-ally stable under these conditions and is formed with greater than 80% ee as estimated from trapping experiments. The less reactive enantiomer (R)-254 is recovered with 41 % yield and 80% ee. 

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