Felkin-Ahn

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 ... 

Radical addition to conjugated systems is an important part of chain propagation reactions. The rate constants for addition of cyclohexyl radical to conjugated amides have been measured, and shown to be faster than addition to styrene. In additions to RCH=C(CN)2 systems, where the R group has a chiral center, the Felkin-Ahn rule (p. 148) is followed and the reaction proceeds with high selectivity. Addition of some radicals, such as (McsSijaSi-, is reversible and this can lead to poor selectivity or isomerization. ... 

The major isomer is assigned the 3R, 4S stereochemistry on the expectation that the addition would occur preferentially with Cram (Felkin-Ahn) selectivity.3 This assignment was confirmed by 1H NMR DNOE experiments on the isobutyraldehyde acetal. 

Substrate control This refers to the addition of an achiral enolate (or allyl metal reagent) to a chiral aldehyde (generally bearing a chiral center at the a-position). In this case, diastereoselectivity is determined by transition state preference according to Cram-Felkin-Ahn considerations.2... 

Although our initial attempts in this direction proved unavailing, our efforts were not completely futile in that we were able to confirm that the critical aldol reaction with S-aldehyde 63 did indeed provide the desired C6-C7 syn and C7-C8 anti relationship (by anti-Felkin Ahn addition) as the major diastereomer. 

Addition of (TMS)3SiH to a-chiral ( )-alkene 7 was found to take place with a complete Michael-type regioselectivity (Reaction 5.8) [26]. A complete syn stereoselectivity was observed for R = Me, and it was rationalized in terms of Felkin-Ahn transition state 8, which favours the syn product similar to nucleophilic addition. 

Murakami and Taguchi utilized a diastereoselective Grignard addition to a substituted-chiral oxazoline aldehyde 524 (Scheme 8.170) in an improved stereoselective synthesis of D-n7 o-phytosphingosine. The good stereoselectivity observed for 525 can be rationalized by a Felkin-Ahn transition state model although a chelation control mechanism could not be mled out. 

The addition of acetate-derived, achiral lithium enolates to monoprotected a-amino aldehydes is controlled by chelation, and leads to a modest stereochemical preference in favor of the 3,4-syn configuration (Table 1, entry a). 18 The formation of the 3, A-syn-product is enhanced by the use of acetate-derived silyl ketene acetals and the addition of titanium(IV) chloride or tin(IV) chloride to the reaction mixture (Table 1, entries b and c). 22-23 The same enolates add stereoselectively to A2 A-dibenzyl a-amino aldehydes but with diastereomeric ratios in favor of the Felkin-Ahn 3,4-anti-product (Table 1, compare entries a and d, and b and f). 22-24 Reverse stereocontrol is observed in the presence of a Lewis acid such as tita-nium(IV) chloride, but the yield is low (Table 1, entry e). 24 ... 

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... 

High yields and enantiopurity have been realized by a highly diastereoselective MPV reduction of protected a-amino aromatic ketones using catalytic amounts of aluminium isopropoxide. The high anti selectivity resulted from the chelation of the (g) nitrogen anion to the aluminium. In contrast, high syn selectivity was obtained with a-alkoxy ketones and other compounds via Felkin-Ahn control.354... 

Coordination with heteroatoms is not an absolute prerequisite for efficacy in directional control. Thus, the stereochemistry observed in the epoxidation of alkoxy-substituted cyclohexenyl ketones 21 has been explained on the basis of a Felkin-Ahn transition... 

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... 

The first example of 1,2-asymmetric induction was reported by Yamamoto and cowork-ers with/V-propyIaldirn ines derived from a-phenylpropionaldehyde (equation 13). The reaction gave mainly the anti product135, consistent with a Felkin-Ahn addition. A 1,3-asymmetric induction took place with the imine prepared from 1-phenylethylamine and isovaleraldehyde, giving a somewhat lower 7 1 diastereoselectivity. 

---