Felkin-Anh addition

The mismatched R/S pairing could lead to the anti,syn adduct through transition state C and the syn,anti adduct via D (Scheme 9.30). The former pathway entails non-Felkin-Anh addition but anti disposed methyl and aldehyde substituents. Transition state D proceeds through the Felkin-Anh mode of carbonyl addition but requires eclipsing of the methyl and aldehyde substituents. This interaction is the more costly one and thus disfavors the syn,anti adduct. 

Reasonable diastereofacial selectivity has also been observed in the addition of the allylstannane referred to above to 2-acetoxy-3,4-octanedione (equation 8). Chemoselective Felkin-Anh addition to the more reactive carbonyl carbon located a to the stereocenter is presumed to occur first, followed by an intramolecular chelation-controlled addition of the allylsilane to the second ketone. 

Nucleophilic additions to tetrahydrofurfural (10 equation 6) proceed under similar constraints. Grignard additions in the presence of HMPT favor formation of product (11), arising from Felkin-Anh addition (Table 5). In the absence of HMPT, nucleophilic addition yields the cyclic chelation control product (12) as the major isomer. ... 

Felkin-Anh addition in the case of the a-silyloxy aldehyde 35 leads to the anti stereochemistry in the homoallylic alcohol 36 as depicted in the antiperiplanar arrangement 37 (Scheme 5.2.8)d ... 

Scheme 5.2.8 Felkin-Anh addition of allyltributyltin to the a-silyloxy aldehyde 35...

Similarly, non-racemic 2,3-epoxyaldehyde 38 displays a preference for Felkin-Anh addition with the bis-stannylated 39 yielding the highly functionalized epoxy-alcohol 40 (Scheme 5.2.9).i ... 

In this case, the reversible coordination of tin with aldehyde favors the closed transition state for Felkin-Anh addition in 339, whereas the jS-chelation model of 340 introduces destabilizing steric interactions owing to placement of the methyl substituent of the chiral allene. Transmetalations of chiral allenylstannanes with InBrs occur with net retention of allene geometry (Scheme 5.2.64). Thus, the starting (P)-286 can also be utilized for a stereoselective reaction with the corresponding (5 )-aldehyde (Scheme 5.2.72, bottom). The enantiomeric alcohol ent-337 is produced via the closed transition state... 

The formation of cM-3,4-dihydroxymethylenecyclopentanes by addition of a dinucleophilic species to an a-diketone acceptor, mediated by tin difluoride, can also be extended to chiral acceptors. Thus, addition to the a-alkoxy diketone 2-acetoxy-3,4-octanedione, in the presence of tin difluoride, affords two products in a 7.5 1 ratio. The major diastereomer is that resulting from Felkin-Anh addition followed by chelation-controlled cyclization14. 

In the case of cycloadditions to the c/.s-acrylate employing tetrakis(triphenylphos-phane)palladium (2mol%) in refluxing toluene, complete diastereoselectivity was observed. The product formed in 69% yield was, once again, that derived from formal Felkin Anh addition to the double bond and the fact that the product was exclusively cw-substituted has direct implications concerning the concertedness of the reaction55. 

Figure 5.7. Analysis of possible transition structures for the aldol addition in Scheme 5.26 (a) The observed topicity (b) boat transition structure postulated by Masamune [127] (c) gauche pentane interaction that destabilizes the Cram (or Felkin-Anh) selectivity of the aldehyde (d) anti-Cram (anti Felkin-Anh) addition via a chelated chair [123].

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