S-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. 

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... 

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, ... 

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). 

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. ... 

Katritzky has published a correction concerning the regioselectivity of the lithiation of indoline lithiocarbamates and dithiolithiocarbamates, which in fact afford the C-3 rather than the presumed C-2 lithio species <97S171>. However, Beak has reported that N-Boc indoline (107) can be metalated selectively at the 2-position with ec-butyllithium (s-BuLi)/(-)-sparteine and the resulting enantioenriched intermediates react readily with electrophiles to provide 2-substituted N-Boc indolines 108 with high enantiomeric ratios (up to 99 1) <97JOC7679>. 

Intramolecular enantiosituselectivity is exemplified by the biosynthetic formation of the mustard oil glucoside sinigrin (60) in horseradish, " the deprotonation of N-Boc-pyrrolidine (62) with sec-butyllithium (s-BuLi)/(-)-sparteine, followed by methylation, "" and, the oxidation of enol 64. Intermolecular enantiosituselective transformations are exemplified by the hydrolysis of racemic N-dodecanoylphenylalanine p-nitrophenyl esters (( )-67) in the presence of tripeptide catalyst (Z)-L-Phe-L-His-L-Leu (68) in each of the latter two cases, only one (externally) enantiotopic carbonyl reacts preferentially. It should be pointed out parenthetically, that as a result of the enantiosituselectivity in these transformations, one has, in effect, kinetic resolution of ( )-67. The electron-impact induced elimination in acetate 71, and the oxidation of 73 exemplify intramolecular diastereosituselective transformations. The epoxidation of the mixture 76/77 is an example of an intermolecular diastereosituselective process at the same time that each substrate is subject to enantiositunonselectivity of the carbonyl sub-sites. 

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. 

A more recent application of this chemistry was reported by Oestreich and Hoppe [74] and involved the enantioselective deprotonation of the enyne carbamate ester 125 with sec-butyllithium in the presence of (-)-sparteine (Scheme 2.41). Removal of the pro-S hydrogen atom led to the corresponding organolithium intermediate, which then underwent a highly enantioselective intramolecular 1,4-addition to the enyne. Protonation of the resulting allenyllithium species 126 provided a 70 30 mixture of the two diastereomeric allenes 127. 

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