Lithium dianions

The lithium dianions of carboxylic acids add to 1-nitrocyclohexene to give, after acid hydrolysis, a mixture of diastereomeric y-oxo acids. The diastereoselectivity of these reactions, however, was not reported7. 

The lithium enolate of AUV-dimethylacetamide underwent addition to 2-aryl-1-nitroethenes to give /faryl-y-nitroamides. The lithium dianions and the trianions of /l-oxo esters and /i,y-dioxo esters undergo addition to 2-aryl-1-nitroethenes to give bicyclic compounds as a single dia-stereomer8. 

Nitroalkenes react with lithium dianions of carboxylic acids or with hthium enolates at -100 °C, and subsequent treatment of the Michael adducts with aqueous acid gives y-keto acids or esters in a one-pot operation, respectively (Eq. 4.52).66 The sequence of Michael addition to nitroalkenes and Nef reaction (Section 6.1) provides a useful tool for organic synthesis. For example, the addition of carbanions derived from sulfones to nitroalkenes followed by the Nef reaction and elimination of the sulfonyl group gives a,P-unsaturated ketones (Eq. 4.53).67... 

Equilibration studies with the lithium dianions of a,/j-unsaturated acids were first carried out by P. E. Pfeffer, L. S. Silbert, J. Org. Chem. 36, 3290 (1971). 

When the lithium dianion was prepared in a completely different manner, viz from an a,j -epoxy ester 8 by treatment of the latter with lithium in liquid ammonia and tetrahydrofuran at - 78 C, alkylation experiments (CH3I, — 40 °C) gave the expected a-alkyl- -hydroxy ester 10, but in a ratio of only 4 1 in favor of the anti-isomer and not in the usual 19 1 ratio15. This result could be interpreted as a direct consequence of the participation of an intermolecularly chelated dianionic enolate such as 7 which gains importance because of the use of ammonia as a cosolvent. 

As a result of the easy accessibility of fi-hydroxy carboxylates, even in their nonraccmic form, and also the predictable and high level of diastereoselectivity in the alkylation of their corresponding dianions, this methodology has become a broadly used synthetic tool (see Tables 1-3). (3S>11, the yeast reduction product of ethyl acetoacetate, is methylated in 68% yield with a d.r. of 95.5 4.5 via the lithium dianion with iodomethane16. 

Naphthalene is known to form a stable lithium dianion at -80°C in tetrahydrofuran (THP) at concentrations lower than 0.5 mol.I-1 (9-12). Unfortunately organolithium compounds are unable to polymerize oxirane (13). Naphthalene can also be metalation by sodium and potassium in THF but no experimental evidence for a dianion of naphthalene sodium or potassium is to be found. Although naphthalene metalation by sodium is thoroughly described ( , lU, 15), very few results about potassium are published (l6, "nT As the reducing power of the alkali metals decreases from lithium (Li/Li+ = 3 02v) to potassium (K/K+ -2.92v) and finally to sodium (Na/Na+ = 2.71v) (l8), it is attractive to study in more detail the naphthalene metalation by in the THF. 

Polyketide synthesis. Polyketides (2) are obtained on reaction of the sodium lithium dianion (1) of methyl acetoacetate with dimethyl glutarates. When refluxed with Ca(OAc)2 in CH3OH, 2 cyclizes to l-oxo-l,2,3,4-tetrahydronaphthalenes in 30-75% yield.1... 

Three further interesting examples, which delineate the utility of [3-lactams in synthesis, have been described recently. In an approach to C-linked glycosyl amino acids, Scheme 37, addition of the lithium dianion 112 to the corresponding N-Boc (3-lactam 111 provides the (3-amino ketone 113 [104],... 

Reaction of the imidoyl phenol 1103 with benzaldehyde proceeds via the lithium dianion 1104 to furnish 2-phenylchroman-4-one in good yield (Scheme 274) <2001T6809>. 

Chiral Auxiliary. (/ ,/ )-( ) has been used as a chiral auxiliary to direct the stereochemistry of addition of a nucleophile to an acrylate moiety. Almost complete stereoselectivity is achieved in the addition of cyclopentanecarboxylic acid lithium dianion to the a-substituted acrylate substrate (eq 14). This methodology allows stereochemical control at the a-position of a p-amino ester and thus complements the methodology described above for the stereoselective formation of p-substituted p-amino esters. 

Instead of malonic esters the lithium dianions of carboxylic acids may also be used, as shown by equation (77). Enantioselective 7-lactone formation has been achieved by Meyers as a ramification of his... 

Fig. 5. 250.13 MHz H NMR spectrum of the lithium dianion of azulene (152 ) in [2H8]tetrahydro-furan. Residual signals are due to the doubly charged dimer I92...

The lithium dianion of 2,4-oxazolidinedione (122) reacts with a-halo ketones to give alkylidene compounds that can be transformed into 3,5-dihydroxy-2(5fl)-furanones (123) by oxidation, followed by hydrolysis (Scheme 47) <92JOC4558>. 

Condensation reactions between the lithium dianion of (S)-ethyl 3-hydroxybutyrate (127 R = OH) and cinnamaldimine (128), in connection with the synthesis of thienamycin, have been reported independently by three groups Georg et Cainelli et a/. " and Hart and Ha. Their results are summarized in Scheme 27 and Table 17 (entries 1-3) analogous reactions of dianion (127) with A -silylimines are discussed in Section 4.1.3.3.1. Of the four possible diastereomeric 3-lactams (129)-(132) that can be produced in this reaction, the two that prevail, (129) and (130), contain the predicted relative stereochemistry at C-3 and C-T. Subsequent inversion of the hydroxy groups of (129) and (130) led to intermediates which constituted formal total syntheses of thienamycin. " " In addition to 3-lactams (129) and (130), trans 3-lactam (131) is sometimes isolated but cis 3-lactam (132) is never observed. The product distributions are not uniform and may reflect the different bases used or the rate at... 

The allylsilane 212 and the common intermediate 215 were made from this monoester (Scheme 28). The lithium dianion of the acid-ester 209 was treated with the aldehyde 210 and the mixture of four diastereoisomeric aldols 211 esterified with diazomethane. The four possible diastereoisomers, present in a ratio of 76 9 9 6 were separated and the 2-trimethylsilylethyl ester group removed by treatment with tetrabutylammonium fluoride. The individual diastereoisomeric... 

The lithium dianion of cyclic thiourea (72) when reacted with alkyl isothiocyanates led to the formation of 7,8-dihydro-l,3-dimethyl-6/f-pyrimido[l,2-a][l,3,5]triazine-2,4(lff,3ff)dithiones (73) and 3,4-dimethyl-l,6-propano-l/f,6/f-3a-thia(S )-l,3,4,6-tetraazapentalene-2,5(3/r,4jH)-dithione (74) (Scheme 5) <86BCJ3693>. 

Several 3-C-branched D-allofuranosyl (7) and 3-C-D-psicopyranosyl (8) derivatives have been obtained from l,2 5,6-di-0-isopropylidene-a-r>-ribo-hexofuranose-3-ulose and l,2 4,5-di-0-isopropylidene-P-D-erythro-2-hexulopyranos-3-ulose respectively by treatment with lithium dianions of the respective carboxylic acids. Synthesis of 3-C-methyl-rhamnose has been reported in connection with the total synthesis of eviminomicin 13,3B4-1, an orthosomicin class antibiotic (see also Section 2 and Chapter 4). ... 

In order to determine if the tacticity is maintained in changing from a monfunctional lithium initiator to a bifunctional lithium initiator, DMA, TrMA, and MMA were all homopolymerized using 1,1,4,4-tetraphenyl butane lithium dianion (DPE Li" )2. 

Scheme 10.19 Deuterium-labeling experiments in the intermolecular carbolithiation of unactivated alkenes with lithium dianions of polycyclic arenes [18b].

The difficulty in the lithium series of these aldol reactions caused Danishefsky to investigate the lithium dianion 59 (R = H) as the nucleophile. Indeed, these reactions did not induce / -elimination and provided quite unexpected results with a high level of stereoselectivity [38]. 

The reaction of 2-bromo-6-lithiopyridine (13) with trialkylboranes gives intermediate boron compounds which are versatile intermediates for the preparation of unsaturated nitriles (Scheme 9). A stereospecific synthesis of dehydronerol utilizes the dianion of 3-methylbut-2-enoic acid as an isoprene functionality (Scheme 10). Lithium dianions from aj8-unsaturated acids generally undergo alkylation reactions at the a-carbon atom. In contrast the dicopper dianions undergo more selective y-alkylation (62—99%) and this ratio is generally higher than with the corresponding esters. A study of various acids and their alkylation with allyl electrophiles showed that allylic electrophiles unsubstituted at the y-carbon react... 

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