Ireland model

In the first step ketone 6 is deprotonated with LDA. Based on the Ireland model,19 it is the Z enolate 39 that forms. This attacks the aldehyde carbon atom in 9 such that the Z lithium enolate leads to the syn isomer. Because of intramolecular chair-like chelate complex 39 the freedom of the transition state is limited and attack on aldehyde 9 is so directed that only the desired diastereomer 10 arises. 

SCHEME 4. The Ireland model to explain the E selectivity in THF (left) and the Z preference in THF/HMPA mixtures (right) during the deprotonation of an ester by LDA23... 

Z-enolate 40 is formed which can be explained by the Ireland model. There, the allyl residue interacts to a lesser extent with the LDA framework than with the sterically demanding dimethyl alkyl residue. Transmetallation with ZnCb delivers the chiral zinc enolate 40. 

Scheme 3.4. Ireland model [39] transition structures for the deprotonation of acyclic carbonyls (after ref. [14]). The gray circles point out the sources of strain in the transition states A - strain increasing as the enolate develops in E(0) and 1,3-diaxial strain in Z(0)i. For structural information from X-ray data, see ref. [29],...

In light of the anomalies described above, it is apparent that the Ireland model is an oversimplification, but a clearer picture has not yet emerged. Indeed, expecting such a simple model to account for kinetic selectivites in a number of solvent systems with a variety of carbonyl substrates and amide bases is asking a lot. There is some evidence that an 8-membered ring transition structure may be involved (deprotonation by a lithium amide open dimer ), and computational studies indicate that neither 6- nor 8-membered ring transition structures bear much resemblance to carbocyclic 6- or 8-membered rings. For a detailed discussion of these issues, see ref. [46]. 

Following the Ireland model (Scheme 3.4), deprotonation gives the Z(0)-enolate. 

If a bulkier base is used, such as lithium tetramethyl piperidide (LTMP), or in the case of ester enolate formation in which the Ri group (actually OR ) is smaller, the ( )-enolate is major. The Ireland model uses the possible six-membered, chair-like, cyclic transition states to help rationalize the stereoselectivity of enolate formation. 

Neural networks have also been used in Slovenia, to model the release characteristics of diclofenac [52] in China, to study release of nifedipine and nomodipine [53] and in Yugoslavia to model the release of aspirin [54], More recently, work in this area has been extended to model osmotic pumps in China [55] and enteric coated tablets in Ireland [56],... 

Hochreiner, H. Wentzell, P. D., Modelling new applications of long period fibre gratings Absorbance measurements, Proceedings Europtrode IX, 30 March 2 April 2008, Dublin, Ireland... 

Detailed investigations indicate that the enolization process (LDA, THF) affords enolates 37 and 38 with at/east 97% (Z)-stereoselection. Related observations have recently been reported on the stereoselective enolization of dialkylthioamides (38). In this latter study, the Ireland-Claisen strategy (34) was employed to assign enolate geometry. Table 10 summarizes the enolization stereo selection that has been observed for both esters and amides with LDA. Complementary kinetic enolization ratios for ketonic substrates are included in Table 7. Recent studies on the role of base structure and solvent are now beginning to appear in the literature (39,40), and the Ireland enolization model for lithium amide bases has been widely accepted, A tabular survey of the influence of the ester moiety (ORj) on a range of aldol condensations via the lithium enolates is provided in Table 11 (eq. [24]). Enolate ratios for some of the condensations illustrated may be found in Table 10. It is apparent from these data that ( )-enolates derived from alkyl propionates (Rj = CH3, t-C4H9) exhibit low aldol stereoselectivity. In contrast, the enolates derived from alkoxyalkyl esters (Rj = CHjOR ) exhibit 10 1 threo diastereo-... 

The infrared spectra of the coal and the various extracts were recorded on a Baird, Model GY-1 (Ireland Mine vitrain concentrate) and on a Perkin Elmer Model 337 spectrophotometer (Bruceton coal). The samples were prepared by the potassium bromide pellet technique. The high resolution proton NMR spectrum of the benzene soluble extract from Ireland Mine vitrain concentrate was recorded on a Varian A-60 spectrometer in 10% deuterated chloroform (CDCh) solution, using tetrametnylsilane internal standard. 

Previously, Ireland-Claisen ester-enolate rearrangement of the corresponding a-propionyloxy-allylsilane led to model system 5.44 Therefore, elaboration to 4 via rearrangement of 15 was pursued. To complete our retrosynthetic analysis, a plausible route to 15 was devised, involving straightforward homologation of 2P,3a-disubstituted cyclohexanone 17 to cyclohexene-carboxaldehyde 16, which in turn undergoes silylanion addition and subsequent acylation (Eq. 8). 

Silyl ketene acetals from esters.1 Ireland has examined various factors in the enolization and silylation of ethyl propionate (1) as a model system. As expected from previous work (6, 276-277), use of LDA (1 equiv.) in THF at —78 -+ 25° results mainly in (E)-2, formed from the (Z)-enolate. The stereoselectivity is markedly affected by the solvent. Addition of TMEDA results in a 60 40 ratio of (Z)- and (E)-2 and lowers the yield significantly. Use of THF/23% HMPA provides (Z)- and (E)-2 in the ratio of 85 15 with no decrease in yield. This system has been widely used for (E)-selective lithium enolate formation from esters and ketones. Highest stereoselectivity is observed by addition of DMPU, recently introduced as a noncar-... 

From results with model systems, Ireland and his colleagues have devised a polyene cyclization route to the pentacyclic enone (124) from the aldehyde (121) (Scheme l).57 Since the enone (124) has already been converted into alnusenone... 

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