Cycloheptanones, nucleophilic additions

In an investigation of the stereoselectivity of nucleophilic addition to larger ring systems, ethyl-, vinyl-, and ethynyl-lithium and -Grignard reagents have been added to 2-(3 -phenylpropyl)cycloheptanone (69). In all cases, the predominant product is the cw-alcohol, and calculations have been used to identify the steric and torsional effects in the transition state that favour this stereochemistry. 

Nucleophilic additions of ethyl-, vinyl-, and ethynyl-lithium and Grignard reagents to a 2-alkyl-substituted cycloheptanone have been found to yield the corresponding cw-cycloheptanol preferentially. The selectivity, which increases with size of the nucleophile, has been attributed to a combination of steric repulsions and torsional effects in the transition state. Application of the MM2 force field to analyse nucleophilic attack of hydride and ethynyl lithium on 2-methylcycloheptanone gave results comparable to those obtained experimentally and from ab initio calculations. 

The stereochemistry of nucleophilic additions to cycloheptanone has been studied by quantum mechanical calculations.160 Employing a Monte Carlo search, 1000 conformations were generated and minimized. The five lowest conformers, labelled A, B, C, D and E, are shown below with their relative energies. The global minimum A is a chair with the carbonyl on the two-carbon stern fragment. The twist conformer B is almost as stable. The three remaining conformers can be roughly characterized as chairs with the carbonyl located at the bow. 

Nucleophilic addition of Ti(IV)-enolates of diazo ketone (136) to cycloheptanone (186) affords alcohol 187 which, on further dehydration with trifluoroacetic anhydride gives a,P-unsaturated carbonyl compounds (188 189) in 58% yield.84... 

Posner recently reported a very simple and fast way to activate epoxides towards nucleophilic opening by ketone lithium enolate anions by use of BF3 Et20 (1 equiv.) [73]. The application of this procedure to the nucleophilic opening of propene oxide with the lithium enolate of 2-cycloheptanone, obtained by the conjugate addition of trimethylstannyllithium to 2-cycloheptenone, afforded the stan-... 

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