Syn-pentane interaction

Fig. 2.34 The two conformations free of destabilizing syn-pentane interaction [215, 216] in 2,4-disubstituted y-amino acid derivatives with like and unlike configuration. According to the nomenclature proposed by Balaram...

Optimal pre-organization of the y-peptide backbone towards the formation of open-chain turn-like motifs is promoted by unlike-y " -amino acid residues. This design principle can be rationalized by examination of the two conformers free of syn-pentane interaction (f and II", Fig. 2.34). Tetrapeptide 150 built from homo-chiral unlike-y -amino acid building blocks 128e has been shown by NMR experiments in pyridine to adopt a reverse turn-like structure stabilized by a 14-mem-bered H-bond pseudocycle [202] (Fig. 2.37 A). 

The presence of a stereogenic center on the aldehyde can strongly inlinence the diastereoselectivity in allylboration reactions, especially if this center is in the a-position. Predictive rules for nucleophilic addition on snch a-snbstitnted carbonyl substrates such as the Felkin model are not always snitable for closed transition structures.For a-substituted aldehydes devoid of a polar substituent, Roush has established that the minimization of ganche-ganche ( syn-pentane ) interactions can overrule the influence of stereoelectronic effects. This model is valid for any 3-monosubstituted allylic boron reagent. For example, althongh crotylboronate (E)-7 adds to aldehyde 39 to afford as the major prodnct the diastereomer predicted by the Felkin model (Scheme 2), " it is proposed that the dominant factor is rather the minimization of syn-pentane interactions between the Y-snbstitnents of the allyl unit and the a-carbon of the aldehyde. With this... 

The stereoinductive effect of the a-substituent is often more powerful when this substituent is a polar group such as an alkoxy or amino gronp. In this instance as well, minimization of syn-pentane interactions with 3-monosnbstituted reagents is important, and the selectivity can be amplified if it acts in concert with other effects. Known models inclnde the stereoelectronic preference... 

Similarity of syn-pentane interactions (left) to 1,3-diaxial interactions in cyclohexane (right). 

In reactions of a-methyl chiral aldehydes with (.. -enolates and Type (2)-crotylmetal reagents like 3, the anti-Felkin addition product is favored due to unfavorable syn-pentane interactions in the Felkin transition state. Thus, in the matched reaction, the (S,5)-3 reagent reacts with aldehyde 40a to provide the anh, syn-dipropionate 45 with 95 5 selectivity. The stereochemical outcome of the reaction can be rationalized by anti-Felkin transition state H, where the nucleophile must approach near the methyl substituent. The mismatched reaction between aldehyde 40b and (R,R)-3 provides a mixture of dipropionates where the syn,syn-dipropionate 46 is only modestly favored (64 36 = sum of all other diastereomers). Transition state I, that rationalizes the formation of the major product, is less favorable as the nucleophile must approach the carbonyl carbon past the larger R substituent. 

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