Deprotonation chiral carbanion

The aim in the previous sections was to generate chiral carbanions with enantiomeric excess by the interaction of (—)-sparteine (11) during the deprotonation. The addition of... 

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

When there is internal return, a deprotonation event escapes detection because exchange does not occur. One experimental test for the occurrence of internal return is racem-ization at chiral carbanionic sites that takes place without exchange. Even racemization cannot be regarded as an absolute measure of the deprotonation rate because, under some conditions, hydrogen-deuterium exchange has been shown to occur with retention of configuration. Owing to these uncertainties about the fate of ion pairs, it is important... 

In the following years, chiral carbanionic reagents of type 4 [4] became valuable reagents in enantioselective synthesis, mainly due to improved access to chiral stannanes of type 1 (Sect. 2.1) and - more importantly - when simple deprotonation procedures became available (Sect. 2.4). 

A carbanion generated at the y-position of a,p-epoxysilanes via a process such as deprotonation can cause (3-ring opening to provide a-silyl alkoxides fScheme 6.4. Eq. 5). Taking into consideration the ready availability of enantiomerically pure epoxides, this method opens the possibility for using epoxides as a source of chiral carbanions via Brook rearrangement. 

Numerous diastereoselective transformations using chiral carbanions derived from a-deprotonation of sulfoxides have been reported [21-23]. In 1973, Maniwa reported the addition of sulfoxide anions to imines [65]. In subsequent work, Kagan established the preparative utility of these additions to provide the corresponding adducts 101 and 103 with useful selectivities and yields (Equations 10 and 11) [66]. 

A major advantage of the sequence presented here is that the aldehyde group is protected at the siloxycyclopropane stage, which allows convenient storage of this stable intermediate. Of equal importance is the valuable carbanion chemistry that can be carried out a to the ester function. Efficient substitution can be achieved by deprotonation with LDA and subsequent reaction with electrophiles.12-13-6 This process makes several a-substituted [1-formyl esters available. Other ring opening variants of siloxycyclopropanes - mostly as one-pot-procedures - are contained in Scheme I. They underscore the high versatility of these intermediates for the synthesis of valuable compounds.6 Chiral formyl esters (see Table, entries 2-5) are of special... 

A much more efficient procedure consists in the deprotonation of prochiral substrates 4 by chiral base 5 (equation 2). The removal of the enantiotopic protons in 4 proceeds through diastereotopic transition states having different energies AG and thus yielding the diastereomeric carbanions 6 and epi-6 in unequal amounts (equation 2). 

The asymmetric (—)-sparteine-mediated deprotonation of alkyl carbamates was unprecedented until discovered in 1990 °. For the first time, protected 1-alkanols could be transformed generally to the corresponding carbanionic species by a simple deprotonation protocol. Moreover, an efficient differentiation between enantiotopic protons in the substrate took place and the extent of stereoselection could be stored in a chiral ion pair, bearing the chiral information at the carbanionic centre. 

The carbanion generated by ot-proton abstraction of a 2-alkyloxazoline is capable of typical enolate chemistry. Thus, the carbanion was found to react with nitriles to give an enamine, with formate esters to give an aldehyde that can be trapped,with chiral sulfinate esters to give chiral sulfoxides,and with alkylating agents. A carbamate-protected aminomethyl chiral oxazoline was deprotonated and alkylated with diastereoselectivities up to 92% de. ... 

In a complementary approach23, aryl ethers with the chiral auxiliary attached to the oxygen atom were reduced to give the enol ethers, subsequent deprotonation with. vcc-butyllithium in THF generated a 2-alkoxy-l,4-cyclohexadienyl carbanion. 

Chiral (5)-2-(methoxymethyl)-l -[( )-3-phenyl-2-propenyl]pyrrolidine obtained from (S)-2-(meth-oxymethyl)pyrrolidine26,30 and ( )-3-bromo-1-phenyl-1-propene, is deprotonated by potassium rert-butoxide/ferf-butyllithium27-28 generating the chiral allyl carbanion, the alkylation of which affords the enamines, which can be hydrolyzed to give 3-alkylated 3-phenylpropanals. 

On the basis that a wide variety of (S)-configurated (a-carbamoyloxy)alkyllithium derivatives are accessible by (—)-sparteine-mediated deprotonation30, Hoppe and coworkers have described the synthesis of enantiomerically and diastereomerically pure cyclopen-tanols 38 by asymmetric cyclocarbolithiation reaction of 5-alkenyl carbamates like 36. Its deprotonation with s-BuLi/(—)-sparteine gives a chiral organolithium which cyclizes to benzyllithium 37 via 5-exo-trig and again with retention of configuration at the carbanionic... 

Chiral lithium bases have been used for enantioselective deprotonation to yield configurationally stable a-oxy carbanions. This holds potential for asymmetric [2,3]-Wittig rearrangement in stereoselective synthesis. Thus, treatment of propargylic ether 72 with (S,S)-3 in THF at — 70 °C to —15 °C afforded propargylic alcohol 73 in 82% yield and in 69% ee of the shown enantiomer96,97. This product was successfully employed as a precursor of (-l-)-Aristolactone (Scheme 55). 

Silylation of a carbanion obtained by enantiotopically differentiating deprotonation of the precursor carbamate in the presence of sparteine leads to the chiral silane 10 with >95 % ee by analogy with the reaction with other electrophiles29 (for analogous derivatives see Section D.8.). 

Matsumura and his coworkers [38] have employed the 2-pyrrolidone anion, in DMF solution, to deprotonate arylacetic acid esters with subsequent oxidative dimerization of the corresponding carbanions. This study includes a useful comparison between the electrochemical and chemical generation of the 2-pyrrolidone anion (by fluoride anion displacement in A-trimethylsilyl-2-pyrrolidone). The advantage lies with the electrochemical route, which gave yields of final product of 80%, compared with the 30% obtained with the chemically generated base (Scheme 10). The overall process, formation of dimethyl 2,3-diphenylsuccinates, is not only efficient and convenient but also operates with high diastereoselectivity when under the control of an oxazolidinone chiral auxiliary (Scheme 10). 

Relatively strong bases are used for the deprotonation of phosphonate reagents, and the phosphonate-stabilized carbanions formed are more basic than the corresponding phosphorane reagents. Such conditions may be incompatible with base-sensitive aldehydes and ketones, causing epimerization of chiral compounds or... 

The reaction must take place after the condensation of two CH3CHO molecules adjacent to each other on different ethylene-diamine residues. For one, the CH3 group has to be syn to the Co(III) ion and in the other anti. The syn methyl is deprotonated in the basic medium and the carbanion produced attacks the imine carbon of the other aldimine. The result is a quadridentate where the chiral C center has been formed stereospecifically by the way the imines are oriented through the chelates. Commencing with A-[Co(en)20x]+, only one isomer should be observed. 

Deprotonation of the chiral 1,2-oxazine (34) by n-butyllithium proceeds with a high degree of stereoselectivity cis to the C-6 substituent subsequent capture of this carbanion with carbonyl compounds also proceeds syn to the C-6 substituent, so that the overall process occurs with retention of configuration at C-4 (Scheme 16). Although the related 1,2-oxazine (3 has not been condensed with carbonyl compounds, it is useful to note that the regioselectivity of its deprotonation can be easily controlled by the size of the base employed. Bulky amide bases preferentially abstract the proton at the exocyclic methyl group, whereas small amide bases such as lithium dimethyiamide preferentially abstract a proton at C-4. ... 

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