Ireland’s model

Ireland s model can be readily applied to the deprotonation of carboxylic amides, as outlined in Scheme 2.12. Here, the crucial interaction comes from the repulsion between the substituent R and the alkyl or cycloalkyl residues R of the amide moiety in transition state 50b. The branching structure ofthe amide moiety is sterically demanding to such an extent that the formation of 50b is de facto completely avoided, and amide deprotonation follows the path through transition state 50a. 

The situation in ketones with relatively small alkyl groups (e.g., 3-propanone) is similar to that of esters (Scheme 2.11). The reaction paths via transition states 48a and 48b (ethyl instead of OR ) with a slight preference for 48b, so that the trans-enolate forms in a moderate excess over the cis-diastereomer. It can be taken as a confirmation of Ireland s model that the sterically more demanding base LTMP enhances the 1,3-diaxial repulsion in 48a, so that the formation of trans-enolates is preferred (Table 2.1, entries 14 vs. 15). The fact that bases of similar bulkiness but different electronic properties, LTMP and lithium (trimethylsilyl)anilide, lead to the opposite stereochemical outcome (entries 15 vs. 17) has been explained by the assumption that the weaker sUylamide base prefers a late expanded Ireland transition state. The stronger base lithium A-f-butyl(trimethylsilyl)amide with similar steric demand leads predominantly to the cis-enolates, in accordance with Ireland s closed transition-state model. If ketones with sterically demanding substituents in the a -position, as in 2,2-dimethyl-3-(trimethylsilyloxy)-4-hexanone... 

Scheme 2.12 Stereochemistry in the formation of amide and ketone enolates according to Ireland s model.

Once Ireland s model had been established, a period followed that brought up fundamental studies of solid and solution structures of preformed enolates (see Chapter 3), but also of meanwhile routinely used amide bases. By 2010, more... 

Compared to the aldol addition, the stereochemical scheme is complicated by the fact that the Michael acceptor may not always and not exclusively adopt the -configuration as shown in 421 but also as Z-diastereomer. The effect of this isomerism has been addressed in a fundamental contribution of Corey and Peterson, which is also one of the first applications of an auxiliary-based stereoselective Michael addition. The chiral lithium enolate 425 that was generated from the propionic ester 424 of phenylmenthol by deprotonation was assumed to adopt the enolate in fcr /is-configuration, in accordance with Ireland s model (cf Section 2.1). The reaction of the enolate with ( )- and (Z)-methyl crotonate led to the Michael products sy/i-426 and a f/-427, respectively. The Michael addition to ( )-crotonate was faster at low temperatures than that of the (Z)-diastereomer and provided higher chemical yields as well as syw-anti-selectivity and induced stereoselectivity. A closed, eight-membered transition state model 428 has been proposed that plausibly explains the opposite stereochemical outcome depending on the double-bond configuration of the Michael acceptor. As the rear side is shielded by the bulky 2-phenyl-2-propyl substituent, the attack of both croto-nates occurs at the Si-face of the enolate 425. Whereas Si-face of ( )-crotonate is selected for the addition of the enolate, the attack to (Z)-crotonate occurs predominantly from the e-face (Scheme 4.92) [206]. 

Ireland s deprotonation model is widely used to rationalize the stereochemistry with various ethyl ketones and bases. " In the absence of additives that solvate the lithium cation such as HMPA, proton transfer occurs via a chair-hke closed transition state. Under these conditions, the (Z)-enolate is disfavored because of the 1,3-diaxial interaction between the Me and the i-Pr group on nitrogen. As the steric requirement of the R group increases, so does the A strain between the R and Me groups in forming the double bond, thus destabilizing the ( )-(0)- relative to the (Z)-(0)-enolate (Table 6.2). 

The EPA was first established on a statutory basis in 1992, with responsibility for environmental monitoring, IPPC and waste licensing and enforcement. The EPA is a independent body, whose decisions are made through a board of four executive directors and an executive director-general. The board does not have any non-executive members. In line with Ireland s social partnership model an advisory group, with representation from the social partners, assists the board. This group does not have decision-making powers. 

According to Ireland s concept, the coordination to HMPA or DMPU causes the cyclic transition state will to become expanded [39], so that 1,3-diaxial repulsion will vanish . Ireland s expanded transition state was disrupted by Heathcock et al. [2c, 38] - into a late, product-like open one (49a or, alternatively 49b). The latter model explains that the allylic strain between the R and OR groups predominates, so that transition state 49b is disfavored in comparison to 49a, as illustrated in Scheme 2.11. A study based on molecular mechanics calculations concluded however that, even in the presence of HMPA, deprotonation with LDA proceeds through a cyclic transition state, though it is less tightly organized than that found in THF [59]. 

Scheme 2.11 Stereochemistry in the formation of ester enolates Ireland s cyclic model (top) and Heathcock s acyclic model. The latter was originally formulated with HMPA that has been replaced here by DMPU which is known to a similar effect.

The selection of transition-state models suitable for rationalizing enolate formation by deprotonation, shown in this overview, give an impression of the complexity of a process that looked simple and convincing in Ireland s intuitive model. Nevertheless - despite all the differences in the deprotonation mechanisms of the various aggregates - its key idea, the cyclic arrangement, seems to be confirmed by the more recent studies. 

Deverell, R. and MacDonnell, K. (2007) Development of a geospatial model to assess proposed bioethanol plant site locations in Ireland. Proceedir s of Phe 15th European Biomass Conference Exhibition. Berlin, 266-268. 

December 1646 London returns a Presbyterian Common Council January 1647 The Scots depart from English soil, leaving the king in parliament s hands March 1647 Parliament begins to move to reduce the size of the New Model and to send men to Ireland... 

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