Nucleophilic addition, diastereoselective cyclopentanones

Similar to cyclohexanones, substituted cyclopentanones also adopt a conformation with the substituents in a sterically favorable position. In the case of 2-substituted cyclopentanones 1 the substituent occupies a pseudoequatorial position and the diastereoselectivity of nucleophilic addition reactions to 1 is determined by the relative importance of the interactions leading to predominant fra s(equatorial) or cw(axial) attack of the nucleophile. When the nucleophile approaches from the cis side, steric interaction with the substituent at C-2 is encountered. On the other hand, according to Felkin, significant torsional strain between the pseudoaxial C-2—H bond and the incipient bond occurs if the nucleophile approaches the carbonyl group from the trans side. 

The diastereoselectivity observed for the conjugate addition to the nonchelated enone sulfoxide (98a) was improved by the use of diorganomagnesium reagents with DME as solvent. Under the same reaction conditions, nucleophilic additions to the corresponding cyclohexenone (101) proceeded with moderate stereoselectivity, giving cyclohexanones (102) as products with somewhat lower enantiomeric excesses than for cyclopentanones (99b) (Scheme 5.35 and Table 5.4) [99]. It should also be noted that in several cases the addition of a highly complexing additive such as 18-crown-6 served to raise the amount of asymmetric induction by about 20% (Table 5.4). 

Generally, in contrast to 2-substituted cyclopentanones, the diastereoselectivity of addition reactions to 3-substituted cyclopentanones is nearly independent of the nucleophile and the substituent in the 3-position. Thus, addition of various Grignard reagents, including ethynyl reagents, to 3-methyl- and 3-ferf-butylcyclopentanone leads to almost the same ratio of diastereomers (Table 3)3,4 6, 27,2s... 

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