Anh-Eisenstein model

Wong, S. S. Paddon-Row, M. N. Theoretical evidence in support of the Anh-Eisenstein electronic model in controlling ji-facial stereoselectivity in... 

Modeisfor the transition structures for nucieophiiic addition to a car-bonyi group according to the Anh and Eisenstein model. (Adapted from reference 343.)... 

Lodge, E. P. Heathcock, C. H. /. Am. Chem. Soc. 1987,109,3353 tested the theoretical models by determining diastereoselectivity in the addition of a lithium enolate to a series of chiral aldehydes. The results were in general agreement with the Anh-Eisenstein adaptation of the Felkin model, but the authors concluded that steric effects were as important as electronic effects (energy of the cr orbital) in determining the transition state for attack of the nucleophile on the carbonyl carbon atom. 

In the Felkin model (5), the important steric interactions involve R1 and R rather than the carbonyl oxygen as assumed by Cram (2-4) and also Karabat-sos (6). On this basis, the preferred mode of attack is 4 + 5 yielding 6, the least strained of six possible staggered conformations (three staggered conformations are possible for each of the diastereoisomers 2 and 3 6 is equivalent to the least strained conformation of 2). Recently, Anh and Eisenstein (7) have concluded from their ab initio calculations that the transition 4+ 5 6 does indeed correspond to the minimum energy transition state. 

Anh and Eisenstein published their first quantum chemical contribution to this issue in 1977. They first constructed a model of the TS for 1,2-addition of hydride to 2-chloropropanal. They placed the hydride ion 1.5 A away from the carbonyl carbon and perpendicular to the CO bond (20). By rotating about the C-C bond in... 

Figure 6.11 Model transition state rotational energy surface for the reaction of H with 2-chloropropanal. The fuU line represents transition states leading to the major product and the dashed line represents those leading to the minor product. Modrhed from the original model proposed by Anh and Eisenstein. ...

Felkin s model relied on reducing steric interactions and strain energy about the carbonyl group. Anh and Eisenstein, however, supplied an alternative reason for the preferred transition-state conformation. The dominant orbital interaction in this reaction is between the highest occupied molecular orbital (HOMO) of the nucleophile and the lowest unoccupied molecular orbital (LUMO) of the carbonyl... 

Unquestionably, the work of Anh and Eisenstein is seminal. Even though their computations were performed at what is today considered an extremely rudimentary level, and as we will see, it is not the last word on the subject, the predictive power of the Felkin-Anh model has become a standard tool in organic chemistry. As argued by Houk, the Ahn-Eisenstein was important not only because it solved an important general problem in stereoselectivity but also because it demonstrated the power of quantum mechanical calculations to solve important problems on real organic systems. ... 

The FeUdn model has been supported and refined by calculations of Anh and Eisenstein [7] as well as by Houle s group [23, 24], The prevailing FeUdn-Anh model takes into account a nonperpendicular Dunitz-Burgi approach of the nucleophile (see above) and it accounts for many stereochemical results. 

The concepts of Felkin, Anh, and Eisenstein are now recognized collectively with the term polar Felkin-Anh model, which is illustrated in Figure The favored approach of the nucleophile allows maximum... 

For this case and many others, the Felkin model was established unequivocally to be energetically preferred, and a variety of details and interpretations were provided. In addition to the role of torsional and steric effects, Anh and Eisenstein found that the most electronegative substituent-that with the lowest-lying a LUMO-would take the conformation anti to the attacking nucleophile. This model and its rationale are now universally known as the Felkin-Anh model. A variety of refinements and extensions occurred in following decades, such as the location of actual transition... 

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