Stable enols from Grignard addition to 1,2-diesters: Serendipity rules

Tetrahedron

Volumn 59, Issue 34, 2003, Pages 6433-6443

  Nicaise, Olivier J C ^a   Mans, Douglas M ^a   Morrow, Andrew D ^a   Hefti, Emilio Villa ^a   Palkovacs, Elizabeth M ^a   Singh, Rajesh K ^a   Zukowska, Malgorzata A ^a   Morin, Matthew D ^a,b  

^a Saint Louis University   (United States)

^b ALMA COLLEGE   (United States)

Author keywords

1,2 diester; Enol carbonate; Enol ester; Grignard reagents; Kinetic stability; Silyl enol ether; Tautomerization; Temperature; Tetrahedral intermediate; ketoester

Indexed keywords

ALCOHOL DERIVATIVE; AMIDE; BROMINE DERIVATIVE; CARBONIC ACID DERIVATIVE; ESTER DERIVATIVE; SILANE DERIVATIVE;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL REACTION KINETICS; GRIGNARD REACTION; INFRARED SPECTROSCOPY; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; TEMPERATURE DEPENDENCE;

EID: 0041701765     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(03)01065-2     Document Type: Article

References (53)

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16. 2,6-Di-tert-butyl-4-methylphenyl or BHT (butylated hydroxytoluene) esters, and 2,6-di-tert-butyl-4-methoxyphenyl or DBHA (dibutylated hydroxyanisole) esters have been used (1) by Heathcock and co-workers for the stereoselective generation of ester lithium enolates and their subsequent use in aldol reactions: (a) Heathcock C.H., Young S.D., Hagen J.P., Pirrung M.C., White C.T., VanDerveer D. J. Org. Chem. 45:1980;3846 (b) Heathcock C.H., Pirrung M.C., Montgomery S.H., Lampe J. Tetrahedron. 37:1981;4087. and (2) by Seebach and co-workers for providing sterically protected, but electronically effective carbonyl groups, and also for the generation of tetrasubstituted ketone lithium enolates: (c) Hassel T., Seebach D. Helv. Chim. Acta. 61:1978;2237 (d) Häner R., Laube T., Seebach D. J. Am. Chem. Soc. 107:1985;5396.
17. 2,6-Di-tert-butyl-4-methylphenyl or BHT (butylated hydroxytoluene) esters, and 2,6-di-tert-butyl-4-methoxyphenyl or DBHA (dibutylated hydroxyanisole) esters have been used (1) by Heathcock and co-workers for the stereoselective generation of ester lithium enolates and their subsequent use in aldol reactions: (a) Heathcock C.H., Young S.D., Hagen J.P., Pirrung M.C., White C.T., VanDerveer D. J. Org. Chem. 45:1980;3846 (b) Heathcock C.H., Pirrung M.C., Montgomery S.H., Lampe J. Tetrahedron. 37:1981;4087. and (2) by Seebach and co-workers for providing sterically protected, but electronically effective carbonyl groups, and also for the generation of tetrasubstituted ketone lithium enolates: (c) Hassel T., Seebach D. Helv. Chim. Acta. 61:1978;2237 (d) Häner R., Laube T., Seebach D. J. Am. Chem. Soc. 107:1985;5396.
18. 2,6-Di-tert-butyl-4-methylphenyl or BHT (butylated hydroxytoluene) esters, and 2,6-di-tert-butyl-4-methoxyphenyl or DBHA (dibutylated hydroxyanisole) esters have been used (1) by Heathcock and co-workers for the stereoselective generation of ester lithium enolates and their subsequent use in aldol reactions: (a) Heathcock C.H., Young S.D., Hagen J.P., Pirrung M.C., White C.T., VanDerveer D. J. Org. Chem. 45:1980;3846 (b) Heathcock C.H., Pirrung M.C., Montgomery S.H., Lampe J. Tetrahedron. 37:1981;4087. and (2) by Seebach and co-workers for providing sterically protected, but electronically effective carbonyl groups, and also for the generation of tetrasubstituted ketone lithium enolates: (c) Hassel T., Seebach D. Helv. Chim. Acta. 61:1978;2237 (d) Häner R., Laube T., Seebach D. J. Am. Chem. Soc. 107:1985;5396.
19. For a recent and very elegant application of reactive enols in synthesis, see the work of Wood and co-workers: (a) Wood J.L., Moniz G.A., Pflum D.A., Stoltz B.M., Holubec A.A., Dietrich H.-J. J. Am. Chem. Soc. 121:1999;1748 (b) Wood J.L., Moniz G.A. Org. Lett. 1:1999;371 (c) Wood J.L., Holubec A.A., Stoltz B.M., Weiss M.M., Dixon J.A., Doan B.D., Shamji M.F., Chen J.M., Heffron T.P. J. Am. Chem. Soc. 121:1999;6326 (d) Moniz G.A., Wood J.L. J. Am. Chem. Soc. 123:2001;5095 (e) Drutu I., Krygowski E.S., Wood J.L. J. Org. Chem. 66:2001;7025.
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37. 10g.
38. 1H NMR spectrum of a commercial sample of 1,2-cyclohexanedione (Aldrich, 97%), and it exhibited a hydroxyl hydrogen signal at 6.02 ppm. This greater value seems to indicate that intramolecular hydrogen bonding in aliphatic enol ester 4b is also unlikely.
39. 1H NMR analysis of the isolated crude material.
40. The results of this on-going study will be reported in the full account of our work on stable enols derived from sterically hindered α-ketoesters.
41. 2/0°C→RT/overnight) afforded trace amounts of the corresponding enol ester 4b and its methyl carbonate 5 in addition to unreacted α-ketoester. An attempt to quench the reaction mixture generated from the 'High T°C/Enol Procedure' with methyl chloroformate did not produce any of the desired methyl carbonate derivative 5.
42. 7b.
43. All attempts to prepare the TBDMS ether of enol ester 4b using TBDMSCl failed, and the α-ketoester 3b was recovered.
44. A similar study with the enol derivative obtained by reaction of 1,2-diester 2b with EtMgBr has documented a more rapid enol-keto tautomerization, thus demonstrating again the effect of substituent size on the stability of the enol.
45. The oily enol ester 4b did not systematically solidify in the freezer.
46. 1H NMR analysis.
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48. 2 column chromatography, a fair amount of a white solid of yet unknown structure.
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53. A colateral benefit of this discovery, thanks to the simplicity of the experimental procedure, has been the development of a microscale experiment for the undergraduate organic chemistry laboratory; see: Nicaise, O. J.-C., Ostrom, K. F., Dalke, B. J. Submitted for publication.