Equatorial organolithiums

Though the destabilisation is much less severe than with a nitrogen lone pair, an amide-stabilised organolithium prefers to minimise the interaction (shown below) between the C-Li bond and the 7i-system of the amide. Hindered amides of piperidines such as 37 are therefore deprotonated to give an equatorial organolithium such as 38.5 4 The equatorially substituted piperidine amide products 39 and 40 are less stable than their axially substituted products owing to the interaction between the new substituent and the pseudoequatorial amide group. Oxidation and equilibration leads to the axial substituted ketone 41.4... 

By oxidising the sulfide to a sulfone, the synthetic versatility of this class of compounds is further increased. Deprotonation of either or both diastereoisomers of 98 leads, under thermodynamic control, to the equatorial organolithium 101 in which a destabilising interaction between the oxygen lone pair and the lithio substituent is avoided. However, lithium-naphthalene reduction of 102 to the organolithium 103 is axially selective because of the stabilisation afforded to the intermediate radical by the axial lone pair. Protonation of the product gives 104.88... 

The axial and equatorial organolithiums ax-69 and eq-69 are both configurationally stable over a period of minutes at -60 °C.37 They react stereospecifically and with retention with electrophiles, as shown below. 

The stannanes 89 and 91 both generate equatorial organolithiums 90 and 92, which can interconvert only by a ring-flipping process. The interconversion does not take place at -78 °C, and the organolithium with the equatorial lithium is clearly the more stable as it quenches with no trace of other stereoisomers even at 0 °C.43 The axially-substituted 92 starts to invert at -40 °C (96% retention) but at -20 °C 35% has inverted, and at 0 °C inversion is complete. 

The equatorial selectivity observed with organolithium reagents is enhanced in diethyl ether as the reaction solvent by the addition of lithium perchlorate (Table l)12. I3C-NMR studies47 indicate that the formation of a complex between lithium perchlorate and the carbonyl group, which also leads to a dramatic enhancement of the rate of the addition reaction, accounts for the increased diastereoselectivity. 

A sequence involving formation of two organolithiums by successive deprotonation and reduction steps allows the introduction of an electrophile either axially or equatorially at the anomeric position of a glycoside.89 Direct reductive lithiation of 98 gives axial 99 and hence... 

Organolithiums a to oxygen atoms within the ring are also configurationally stable at -78 °C in THF. The axial and equatorial stannanes ax-7 0 and eg-70, for example, give organolithiums 71 which retain their stereochemistry over periods of up to 50 min in THF at -78 °C, and can be quenched stereospecifically with aldehydes.38... 

In each case, stereoselectivity can be explained by assuming that the reaction proceeds through a chair-like transition state, in which there are interactions between the two ends of the C-Li and C=C bonds, and in which the substituents all occupy pseudo-equatorial positions (structures 338, 339 and 340). The same transition state model suffices to explain the stereoselectivities of the furan and pyrrolidine forming reactions above. Stereoselectivity in the cyclisations of the selenide-derived tertiary organolithiums would arise from a conformation with a precedented pseudo-axial phenyl ring. 

Lactols and their acetals can be transformed easily into their 2-arylsulfonyl derivatives 337 by reaction with a sulfinic acid under Lewis acid activation. The corresponding organolithiums are prepared by deprotonation with n-BuLi or LDA and, after reaction with electrophiles, a /(-elimination of sulfinic acid afforded a cyclic a-substituted enol ether514,547,548. 2-Lithio-2-(arylsulfonyl)tetrahydropyrans equilibrated to give mainly the anomer with the lithium atom at the equatorial position549. 

Directed lithiations of a,3- and -y.b-unsaturated amides " have been extensively studied. Illustrative examples are shown in Scheme 44. Prior complexation of the alkyllithium base with the amide carbonyl oxygen directs the base to the thermodynamically less acidic -position in a,3-unsaturated amide (31), which adds to benzophenone and subsequently lactonizes. Analysis of the NMR spectrum reveals that the organolithium added the benzophenone in the equatorial position. A Afferent kinetic deprotonation is seen in y,8-unsaturated amide (32), where -lithiation to form an allylic anion predominates over a-lithiadon to form an enolate. > Addition of the lithium anion to acetone affords poor regioselectivity, but transmetalation to magnesium before carbonyl addition yields a species which adds exclusively at the 8-position. ... 

Chemoselective organolithium reactions. The blocking of the equatorial plane of cyclohexanones by the bulky Lewis acid forces attack by nucleophiles from the axial direction. Also for steric reasons dialkyl ketones are less reactive than cyclohexanones in which C-2 and C-6 are not substituted. 

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