Enantioselective lithiation sparteine complexes

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... 

Hoppe and coworkers succeeded in crystallization of lithiated 1 -methyl- or 1 -butyl-3H-indene and (-)-sparteine complexes (Table 12) [101]. The crystallization preferentially gave one of the stereoisomers which was reacted with acid chlorides to afford acylated indenes with high enantioselectivity. In a comparison of the absolute configuration of the acylated indenes with that of the crystallized complexes determined by the X-ray analysis, it was found that the reaction with acid chlorides proceeds with retention of configuration at the lithiated car-banion. 

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... 

Desymmetrisation by enantioselective ortholithiation has been achieved with ferrocenylcarboxamides 434,187 and also (with chiral lithium amide bases) a number of chromium-arene complexes.188 The chromium arene complex 435, on treatment with s-BuLi-(-)-sparteine, gives 436 enantioselectively, and reaction with electrophiles leads to 437. However, further treatment with r-BuLi generates the doubly lithiated species 438, in which the new organolithium centre is more reactive than the old, which still carries the (-)-sparteine ligand. Reaction of 438 with an electrophile followed by protonation therefore gives ent-431.m... 

This transformation has been extended recently by the development of methods for the enantiotopos selective lithiation of a prochiral 2-butenylcarbamate and the subsequent formation of chiral 2-butenyltitanium reagents from these species (Scheme 10-94) [180]. The reaction of -2-butenylcarbamate 279 with a solution of 5ec -butyllithium and (-)-sparteine generates a crystalline lithium complex 280-sparteine. Upon addition of 4 equivalents of Ti(Oi-Pr)4, a homogeneous titanium complex 283 (see below) is formed. The titanium reagent is then allowed to react with aldehydes to produce diastereomerically pure homoallylic alcohols 282 with good to high enantioselectivity. The high enantioselectivity observed in the... 

Unlike lithiated tetrahydroisoquinolines, a-lithio derivatives of saturated heterocycles are configurationally stable [202-204] (review [163]), and they have a considerably higher kinetic barrier to deprotonation. Nevertheless, there have been a number of activating groups developed for the alkylation of a-lithio amines. In 1991, Beak showed that the complex of sparteine and sec-butyllithium enantioselectively deprotonates BOC-pyrrolidine, and that the derived organolithium is a good nucleophile for the reaction with several electrophiles, as shown in... 

Although early studies by Nozaki examined (-)-sparteine 2 in the asymmetric lithiation of isopropylferrocene (as noted in Sect. 1.1 above), the first enantioselective generation of planar chirality in good ees using an organolithium (Clay-don, in this volume) was reported by Uemura in 1994 in the lithiation of tricar-bonyl(q -phenyl carbamate)chromium complexes using chiral diamines. After quenching with electrophiles, enantioenriched (o-substituted phenyl car-bamate)chromium complexes were obtained in up to 82% ee (Scheme 19) [61]. 

In the majority of cases, the deprotonation of carbamates occurs in the presence of diamines (TMEDA, sparteine or like-sparteine diamine). Complex s-BuLi with the chiral (-)-sparteine efficiendy and enantioselectively deprotonates N-Boc-pyrrolidine (127), but the same base complex is less effective with N-Boc-piperidine. So, lithiation of N-t-Boc-piperidine with sec-BuLi-(-)/sparteine requires 16 h for completion of the deprotonation and after subsequent addition of trimethylchlorosilane, the yield of (S)-195 is detected to be only 8% (133). However, the replacement of sparteine by other diamine results in the increased yield of (S)-195 (135). 

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