Current Science

Open Access Open Access  Restricted Access Subscription Access

Diverse Behaviour of C-3 Enolates Derived from Configurationally Isomeric Trimethyl 1-Methylcyclohexane-1,2,3-Tricarboxylates


Affiliations
1 Saras Kshetra, Machohalli, Bengaluru - 560 091, India
 

Configurational relationships among three, A, B and C, of the four possible isomers of trimethyl 1-methylcyclohexane-1,2,3-tricarboxylate imply that A and C should form a common C-3 enolate. While methylation of tritylsodium-formed A C-3 enolate gives one of the two possible meso forms and B C-3 enolate gives the racemic product, C does not form an enolate. 1H NMR-assigned preferred conformations of A and B show that their C-3 enolates form Na+ complexes stabilized by the C-1 syn, axial ester group, while the C-1 methyl in C hinders removal of the C-3 proton, thus preventing enolate formation. Early treatment of A enolate with methyl iodide leads to one of two possible meso methylated products, while late treatment gives the racemic form, also a product of B methylation. A gradual rise in C/A ratio is seen on protonating A enolate, though only a ring flip is involved, this phenomenon is attributed to the intervention of a slow Na+ deand re-complexation process. A unified explanation emerges under the premise that while the methylating agent approaches the enolate from the non-hindered face anti to Na+, the proton is guided by Na+ towards syn approach.

Keywords

Cyclohexane-1,2,3-Triesters, α-Enolate-Formation, Methylation, Protonation, Solvent Cavity
User
Notifications
Font Size

  • Balasubrahmanyam, S. N., The 'C-11 Acid' and the stereochemistry of abietic acid. Resonance, 2015, 20, 217–233; http://www.ias.ac.in/article/fulltext/reso/020/03/0217-0234.

  • Ruzicka, L. and Meyer, J., Hoehere Terpenverbindungen XVII. Ueber die gelinde Einwirkung von Kaliumpermanganat auf die Abietinsaeure. Helv. Chim. Acta, 1923, 6, 1097–1108; doi: 10.1002/hlca.192300601128; Ruzicka, L., Meyer, J. and Pfeiffer, M., Hoehere Terpenverbindungen XXVI. Ueber den Abbau der Abietinsaeure mit Kaliumpermanganat und Ozon. Helv. Chim. Acta, 1925, 8, 637–650; doi:10.1002/hlca.19250080191; Ruzicka, L., Goldberg, M. W., Huyser, H. W. and Seidel, F., Hoehere Terpenverbindungen XLVIII. Ueber die Konstitution der durch Oxydation der Abietinsaeure gewonnenen Tricarbonsaeuren C11H16O6 und C12H18O6. Ein Beitrag zur Kenntnis des Kohlenstoffge rUestes der Abietinsaeure. Helv. Chim. Acta, 1931, 14, 545–570; doi: 10.1002/hlca.19310140154; Ruzicka, L., de Graaff, G. B. R., Goldberg, M. W. and Frank, B., Polyterpene und polyterpenoide LXXI. Ueber den oxydativen Abbau der Dextro-Pimarsaeure. Helv. Chim. Acta, 1932, 15, 915–923; doi:10.1002/hlca.19320150196; Ruzicka, L. and Bernold, E., Zur Kenntnis der Diterpene. (48. Mitteilung). Ueber den Abbau der Agathen‐disaeure mit Kaliumpermanganat. Helv. Chim. Acta, 1941, 24, 931–939, doi:10.1002/hlca.194102401111.

  • Barton, D. H. R. and. Schmeidler, G. A., The application of the method of electrostatic energy differences. Part I. Stereochemistry of the diterpenoid resin acids. J. Chem. Soc., 1948, 1197–1203; doi:10.1039/JR9480001197.

  • Ruzicka, L., The isoprene rule and the biogenesis of terpenic compounds. Cell. Mol. Life Sci., 1953, 9, 357–367; doi:10.1007/ BF02167631.

  • Banerjee, D. K., Balasubrahmanyam, S. N. and Ranganathan, R., Syntheses of the trans, meso- and racemic C-11 acids, degradation products of diterpene acids. J. Chem. Soc. (C), 1966, 1458–1467; doi:10.1039/J39660001458; Banerjee, D. K. and Balasubrahmanyam, S. N., The synthesis of the trans, trans and cis, trans isomers of the C-11 acid, degradation products of abietic and agathic acids. Bull. Natl. Inst. Sci. India, 1968, 37, 114–124.

  • Linstead, R. P. and Millidge, A. F., Fused carbon rings. Part IX. The synthesis of stereoisomeric 1-methyl-cyclohexane-1:2-dicarboxylic acids and of various methyl cyclo hexane carboxylic acetic acids. The influence of the angular methyl group on the stability of their anhydrides. J. Chem. Soc., 1936, 478–486; doi:10.1039/JR9360000478.

  • Balasubrahmanyam, S. N. and Balasubramanian, M., On the conformations of isomeric trimethyl 1-methylcyclohexane-1,2,3-tricarboxylates. J. Chem. Soc. (B), 1970, 212–217; doi:10.1039/J29700000212.

  • Belostotskii, A. M., Conformational Concept for Synthetic Chemist's Use: Principles and in Lab Exploitation, World Scientific: Singapore, 2016, ISBN: 978-981-281-409-8.

  • Zook, H. D. and Russo, T. J., Chemistry of enolates. iv. Solvents for enhanced carbanion activity, J. Am. Chem. Soc., 1960, 82, 1258–1259 doi:10.1021/ja01490a064; Zaugg, H. E., Horrom, B.

  • W. and Borgwardt, S., Specific solvent effects in the alkylation of enolate anions. I. The alkylation of sodiomalonic esters with alkyl halides, J. Am. Chem. Soc., 1960, 82, 2895-2903; doi:10.1021/ja01496a055; Zaugg, H., Horrom, B. and Borgwardt, S., Additions and corrections – specific solvent effects in the alkylation of enolate anions. I. The alkylation of sodiomalonic esters with alkyl halides. J. Am. Chem. Soc., 1960, 82, 6429–6431, doi:10.1021/ja01509a632; Raban, M. and Haritos, D. P., NMR studies of enolate anions. 6. A carbon-13 NMR study of alkali metal chelation by 3-alkylacetylacetonates. J. Am. Chem. Soc., 1979, 101, 5178– 5182; doi:10.1021/ja00512a011; Parker, A. J., The effects of solvation on the properties of anions in dipolar aprotic solvents. Q. Rev. Chem. Soc., 1962, 16, 163–187; doi.org/10.1039/ QR9621600163; Jayaraj, K., Studies in the stereochemistry of alkylation – importance of gegenion co-ordination, Ph D thesis, Indian Institute of Science (IISc), Bengaluru, 1981, p. 20.

  • Balasubrahmanyam, S. N. and Jayaraj, K., Syn-axial and counter-ion coordination factors in the methylation of 6-membered cyclic esters. Indian J. Chem. (B), 2003, 42, 1098–1110.

  • Kawabata, T., Kawakami, S. and Fuji, K., Enantioselective α-allylation of α-phenylalanine derivative under the control of aggregation of a chiral nonracemic enolate. Tetrahedron Lett., 2004,. 43, 1465–1467.

  • Cram, D. J., Fundamentals of Carbanion Chemistry, Academic Press, New York, USA, 1965, pp. 85–105; 138–158.

  • Chaissaing, G., Lett, R. and Parquet, A., Convincing evidence that the alkylation stereochemistry of cyclic

  • α-lithio sulfoxides is governed by their chelated structure, Tetrahedron Lett., 1978, 471–474; Lett, R., Chaissaing, G. and Marquet, A., Structure of sulfurstabilized carbanions. A 13C NMR study of some

  • α-lithio-sulfoxides and sulfones. J. Organomet. Chem., 1976, 111, C17;https://doi.org/10.1016/S0022-328X(00)87137-5

  • Narasimha Bharathi, S., Stereochemical investigations in chiral ethyl esters, Ph D thesis, IISc, Bengaluru, 1981, pp. 56–57; 96–97.

  • Johnson, F. and Malhotra, S. K., Steric interference in allylic and pseudo-allylic systems. I. Two stereochemical theorems. J. Am. Chem. Soc., 1965, 87, 5492–5493; Steric interference in allylic and pseudo-allylic systems. II. Stereochemistry of exocyclic enolate anion protonation. J. Am. Chem. Soc., 1965, 87, 5493–5494; doi:10.1021/ja00951a046 and doi:10.1021/ja00951a047; Johnson, F., Allytic strain in six-membered rings. Chem. Rev., 1968, 68, 375–413; doi:10.1021/cr60254a001; Johnson, F. and Dix, D. T., Allytic (1,3) strain. Defence. J. Am. Chem. Soc., 1971, 93, 5931–5932; doi:10.1021/ja00751a077.

  • Letsinger, R. L., Formation of optically active 1-methylheptyl-lithium. J. Am. Chem. Soc., 1950, 72, 4842; doi:10.1021/ja01166a538

  • March, J., Advanced Organic Chemistry – Reactions, Mechanisms and Structure, Wiley Eastern, New Delhi, 1986, 3rd edn, pp. 156; 517–518.

  • Zhao, H., Hsu, D. C. and Carlier, P. R., Memory of chirality: an emerging strategy for asymmetric synthesis. Synthesis, 2005, 1–16; doi:10.1055/s-2004-834931; Wolf, C., Dynamic Stereochemistry of Chiral Compounds: Principles and Applications, Royal Society of Chemistry, London, 2008; doi:10.1039/9781847558091.

  • Kawabata, T., Suzuki, H., Nagae, Y. and Fuji, K., Achiral nonracemic enolate with dynamic axial symmetry: direct asymmetric α-methylation of α-amino acid derivatives. Angew. Chem. Int. Ed. Engl., 2000, 39, 2155–2157; doi:10.1002/1521-3773(20000616).


Abstract Views: 333

PDF Views: 93




  • Diverse Behaviour of C-3 Enolates Derived from Configurationally Isomeric Trimethyl 1-Methylcyclohexane-1,2,3-Tricarboxylates

Abstract Views: 333  |  PDF Views: 93

Authors

S. N. Balasubrahmanyam
Saras Kshetra, Machohalli, Bengaluru - 560 091, India

Abstract


Configurational relationships among three, A, B and C, of the four possible isomers of trimethyl 1-methylcyclohexane-1,2,3-tricarboxylate imply that A and C should form a common C-3 enolate. While methylation of tritylsodium-formed A C-3 enolate gives one of the two possible meso forms and B C-3 enolate gives the racemic product, C does not form an enolate. 1H NMR-assigned preferred conformations of A and B show that their C-3 enolates form Na+ complexes stabilized by the C-1 syn, axial ester group, while the C-1 methyl in C hinders removal of the C-3 proton, thus preventing enolate formation. Early treatment of A enolate with methyl iodide leads to one of two possible meso methylated products, while late treatment gives the racemic form, also a product of B methylation. A gradual rise in C/A ratio is seen on protonating A enolate, though only a ring flip is involved, this phenomenon is attributed to the intervention of a slow Na+ deand re-complexation process. A unified explanation emerges under the premise that while the methylating agent approaches the enolate from the non-hindered face anti to Na+, the proton is guided by Na+ towards syn approach.

Keywords


Cyclohexane-1,2,3-Triesters, α-Enolate-Formation, Methylation, Protonation, Solvent Cavity

References





DOI: https://doi.org/10.18520/cs%2Fv116%2Fi12%2F1975-1986