Felkin—Ahn model

Another model can be used to predict diastereoselectivity, which assumes reactant-like transition states and that the separation of the incoming group and any electronegative substituent at the a carbon is greatest. Transition state models 45 and 46 are used to predict diastereoselectivity in what is known as the Felkin Ahn model ... 

Sterically bulky OR groups (trityloxy or Bu PtbSiO) gave tlie yyn-diastereoisomer (119) either exclusively or predominantly. The, vv -selectivity was rationalized by a modified Felkin-Ahn model (121).94... 

Chiral centres within the nucleophile or the conjugated double bond will control the stereochemistry of the chiral centres that are formed. For example, the Felkin-Ahn model has been applied to nucleophilic 1,4-addition to an ,/3-unsaturatcd carbonyl bearing a... 

Diastereoselective addition of organometallic reagents to a-chiral aldehydes usually follows the Cram s rule or Felkin-Ahn model. However, the sense ot the Odiastereoselectivity in the catalysed addition of dialkylzinc to a-chiral aldehydes is determined not by the chirality of aldehyde but by the configuration of the chiral catalysts. By choosing the appropriate enantiomer of the chiral catalyst, one can obtain the desired diastereomer from the diastereoselective addition of dialkylzincs to a-chiral aldehydes.18 Either of the diastereomers of protected chiral 1,2-diols and 1,3-diols is synthesized using the appropriate enantiomer of the chiral catalysts [(15,2f )-l, (R,R)-15, and their enantiomers] from the addition of diorganozincs to protected a-hydroxy-19 and P-hydroxyaldehydes (Scheme 12.3).20... 

Fig. 6. Felkin-Ahn model for Grignard addition to 5-formyl-2-isoxazolines.

Prediction for the reduction of cyclic ketones on the basis of the Cram, Karabatsos and Felkin-Ahn models is usually unreliable and a simple model has yet to emerge. 

However, CeCb is a poor chelating Lewis acid. The stereochemistry of the reaction is reversed in this case, which can be explained on the basis of an open-chain Felkin-Ahn model. The anti-alcohol 6.68 is produced by the attack of hydride from the less hindered side to the most stable conformation, C of CeCb complex. The D conformation is less stable than C (Scheme 6.26). 

Although the stereochemistry of the organometal addition reactions to carbonyls with a-alkyl ( i-cally a-methyl) substituents is explained mostly by the Felkin-Ahn model, different phenomena are observed with a-alkoxy- or a-hydroxy-caibonyls, which make the opposite ar-face sterically more... 

In the asymmetric alkylation of a-chiral aldehydes using dialkylzinc reagents, the stereochemistry is controlled by the configuration of the chiral catalyst, not by the stereochemistry in the a-position. It is different from the diastereoselec-tive alkylation using other organometallic reagents where the stereochemistry follows from Cram s rule or the Felkin-Ahn model. Each diastereomer with high ee was obtained by the choice of the appropriate enantiomer of chiral catalyst [(IS, 2R)- or (li ,2S)-DBNE 1] (Scheme 6) [18]. 

The most intensely studied aldol addition mechanisms are those beUeved to proceed through closed transition structures, which are best understood within the Zimmerman-Traxler paradigm (Fig. 5) [Id]. Superposition of this construct on the Felkin-Ahn model for carbonyl addition reactions allows for the construction of transition-state models impressive in their abiUty to account for many of the stereochemical features of aldol additions [50a, 50b, 50c, 51]. Moreover, consideration of dipole effects along with remote non-bonding interactions in the transition-state have imparted additional sophistication to the analysis of this reaction and provide a bedrock of information that may be integrated into the further development and refinement of the corresponding catalytic processes [52a, 52b]. One of the most powerful features of the Zimmerman-Traxler model in its application to diastereoselective additions of chiral enolates to aldehydes is the correlation of enolate geometry (Z- versus E-) with simple di-astereoselectivity in the products syn versus anti). Consequently, the analyses of catalytic, enantioselective variants that display such stereospecificity often invoke closed, cyclic structures. Further studies of these systems are warranted, since it is not clear to what extent such models, which have evolved in the context of diastereoselective aldol additions via chiral auxiliary control, are applicable in the Lewis acid-catalyzed addition of enol silanes and aldehydes. 

The presence of a chiral acetal, aminal or oxathiane in the vicinity of a carbonyl group can direct the reduction of a ketone toward a diastereoisomeric alcohol, whether or not chelation is operative. For example, the LiAlHf or Li 5-BU3BH reductions shown in Figure 6.13 give predominantly the diastereoisomer predicted by the Felkin-Ahn model while reductions with DIBAL or LiAlH4/MgBr2 give predominantly the diastereoisomer predicted by the chelation model [87,94, 213, 226],... 

As chemists considered the origin of this diastereoselectivity, the reactant conformation that is considered to be the most important one has changed. The currently preferred Felkin-Ahn model places the largest substituent perpendicular to the carbonyl group. The major product results from the nucleophile approaching opposite to the largest substituent. This is the same product as predicted by the Cram model, although the interpretation is different. 

One broad generalization is that when steric interactions are dominant the Felkin-Ahn model is predictive. Thus steric approach control, the idea that the approaching nucleophile will approach the carbonyl group from the least hindered direction, is the first guiding principle. ... 

---