73873-50-4Relevant academic research and scientific papers
Folding strain stereocontrol in cyclohexane ring formation by means of an intramolecular ester enolate alkylation reaction
Tokoroyama, Takashi,Kusaka, Hisashi
, p. 2487 - 2502 (2007/10/03)
Diastereoselectivity in the cyclization of ethyl 7-bromo-2-methylheptanoates with an additional substituent at various positions in the chain, by LDA treatment, was investigated in connection with the concept of folding strain stereocontrol. Cyclization of 3-, 4-, and 6-methyl-substituted substrates revealed high selectivity, which demonstrates the prevalence of folding strain stereocontrol and the usefulness of this approach for stereoselective ring construction. In particular, reactions of the latter two substrates resulted in the stereodivergent preparation of diastereomeric 1,3-dimethylcyclohexanecarboxylates. In the case of the 5-methyl-substituted substrate, the selectivity of ring closure was only moderate. 1H and 13C NMR spectroscopic data were useful for determining the conformation of 1-methylcyclohexanecarboxylate derivatives. The origin of the diastereoselectivity was examined through the qualitative comparison of the strain in the diastereomeric folding in the transition state. Various factors that might affect stereoselectivity were examined in the cyclization of 5-substituted substrates to better understand this concept. As predicted, the selectivity increased as the substituent became bulkier: Ph Me ≈ Et ≤ i-Pr t-Bu. The effects of other factors - solvent, base counter cation, and leaving group - on selectivity agree with results predicted from the reactivity-selectivity relationship.
Stereochemistry of Alkylation of Carboxylic Acid Salt and Ester α Anions Derived from Cyclic Systems.
Krapcho, A.Paul,Dundulis, Edward A.
, p. 3236 - 3245 (2007/10/02)
A stereochemical study of the alkylation of α-lithiated carboxylate salts and esters has been performed.The α anions derived from the bicyclic acids exo-1, endo-1, and 7 (R=H) and the esters 4 and 7 (R=CH3) yield predominantly exo alkylation.As an example, the α anion derived from ester 7 (R=CH3) on treatment with CH3I yields exo-8 (R=R'=CH3) and endo-9 (R=R'=CH3) in a 97:3 ratio, a highly stereoselective reaction.Addition of TMEDA to the reactions involving the α anions derived from exo- or endo-1 did not change the stereochemical alkylation results.The α anions derived from the substituted cyclohexanecarboxylic acids 10, 13, 16, 19, or 22 (where R=H in each case) on methylation yield more axial methylation (axial/equatorial ratios of 0.4-2.7) than the α anions derived from the methyl esters corresponding to these acids.The α anions from the esters yield predominantly equatorial methylated products (e/a ratios varying from 4 to 9).The reasons for the different stereochemical results are discussed.
