An Investigation of the Enolization and Isomeric Products Distribution in the Water Promoted Aldol Reaction of Tropinone and Granatanone

The exo,anti/exo,syn-diastereoselectivity of water promoted direct aldol reactions of tropinone and granatanone (pseudopelletierine) is strongly dependent on the amount of water added and aromatic aldehyde used. DFT methods were applied to calculate the free energies of tropinone and granatanone enols, transition states, and isomeric aldol products. A theoretical model was verified by comparison of results from several DFT methods and functionals with experiments. The 6-31g(d)/CPCM method proved most suited to the problem, although all methods tested predicted similar trends. Explicit inclusion of a water molecule bonded to the amino ketones resulted in increased stability of the enol forms. The dependence of the anti/syn-diastereoselectivity on the amount of water used may be rationalized on the basis of change in the polarity of the reaction medium. The predicted stabilities of competing products agreed with experimental results supporting the notion of thermodynamic control. The isomeric products distributions for the aldol reaction of several aromatic aldehydes in solventless (neat) conditions were accurately calculated from free energies of the aldol addition step in the gas phase using B3LYP/6-31g(d) method and in aqueous conditions using the CPCM-B3LYP/6-31g(d) model. Our methodology can be useful for predicting the outcome of this type of aldol reactions.

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Efficient Construction of 4-hydroxy-4-arylbutan-2-ones through an Enantioselective Aldol Reaction Mediated by a Recoverable Proline-Based Chiral Ionic Liquid

Journal of the chemical society of pakistan ◽

10.52568/000629 ◽

2020 ◽

Vol 42 (2) ◽

pp. 243-243

Author(s):

Dao Cai Wang Dao Cai Wang ◽

Cong Wu Cong Wu ◽

Chi Zhang Chi Zhang ◽

Fang Zhen Zhou Fang Zhen Zhou ◽

Hang Song and Xiao Peng Liu Hang Song and Xiao Peng Liu

Keyword(s):

Ionic Liquid ◽

Column Chromatography ◽

Aldol Reaction ◽

Reaction Medium ◽

Aromatic Aldehydes ◽

Catalytic Method ◽

Mild Conditions ◽

Satisfactory Performance ◽

Efficient Construction ◽

Chiral Ionic Liquid

Chiral ionic liquid derived from L-proline worked as an excellent organocatalyst for the enantioselective aldol reaction of aromatic aldehydes and acetone. The reaction was conducted in the presence of [BMIM][BF4] as reaction medium. The substrate scope of aldol reaction was successfully explored for various aromatic aldehydes under the mild conditions. The generated aldol products were separated by column chromatography with moderate to good yields as well as enantioselectivities. The main advantage of this catalytic method was that the catalyst and solvent could be recovered at the same time and reused for at least five times with satisfactory performance.

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Carbon−Carbon Bond Formation

Modern Organic Synthesis in the Laboratory ◽

10.1093/oso/9780195187984.003.0011 ◽

2008 ◽

Author(s):

Jie Jack Li ◽

Chris Limberakis ◽

Derek A. Pflum

Keyword(s):

Natural Products ◽

Asymmetric Synthesis ◽

Aldol Condensation ◽

Bond Formation ◽

Aldol Reaction ◽

Aldol Reactions ◽

Academic Press ◽

Carbon Carbon Bond ◽

Stereogenic Centers ◽

Aldol Addition

Reviews: (a) Vicarion, J. L.; Badia, D.; Carillo, L.; Reyes, E.; Etxebarria, J. Curr. Org. Chem. 2005, 9, 219-235. (b) Mahrwald, R. Ed. In Modern Aldol Reactions; Wiley-VCH: Weinheim, 2004; Vol. 1., pp. 1-335 (c) Mahrwald, R. Ed. In Modern Aldol Reactions; Wiley-VCH: Weinheim, 2004; Vol. 2., pp. 1-345.(d) Machajewski, T. D.; Wong, C.-H. Angew. Chem. Int. Ed. 2000, 39, 1352-1375. (e) Carriera, E. M. In Modern Carbonyl Chemistry; Otera, J.; Wiley-VCH: Weinheim, 2000; Chapter 8: Aldol Reaction: Methodology and Stereochemistry, 227-248. (f) Paterson, I.; Cowden, C. J.; Wallace, D. J. In Modern Carbonyl Chemistry; Otera, J.; Wiley-VCH: Weinheim, 2000; Chapter 9: Stereoselective Aldol Reactions in the Synthesis of Polyketide Natural Products, pp. 249-298. (g) Franklin, A. S.; Paterson, I. Contemp. Org. Synth. 1994, 1 317-338. (h) Heathcock, C. H. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: Orlando, Fl.; 1984; Vol. 3., Chapter 2: The Aldol Addition Reaction, pp. 111-212. (i) Mukaiyama, T. Org. React. 1982, 28, 203-331. Since the early 1980s, aldol condensations involving boron enolates have gain great importance in asymmetric synthesis, particularly the synthesis of natural products with adjacent stereogenic centers bearing hydroxyl and methyl groups. (Z)-Boron enolates tend to give a high diastereoslectivity preference for the syn-stereochemistry while (E)-boron enolates favor the anti-stereochemistry. Because the B-O and B-C bonds are shorter than other metals with oxygen and carbon, the six membered Zimmerman–Traxler transition state in the aldol condensation tends to be more compact which accentuates steric interactions, thus leading to higher diastereoselectivity. When this feature is coupled with a boron enolate bearing a chiral auxillary, high enantioselectivity is achieved. Boron enolates are generated from a ketone and boron triflate in the presence of an organic base such as triethylamine. Reviews: (a) Abiko, A. Acc. Chem. Res. 2004, 37, 387-395. (b) Cowden, C. J. Org. React. 1997, 51, 1-200.

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Chiral Thiazolidine based Organocatalysts: Synthesis and Application in Asymmetric Aldol Reactions

Letters in Organic Chemistry ◽

10.2174/2210681209666190807155816 ◽

2020 ◽

Vol 17 (5) ◽

pp. 372-380

Author(s):

Ana Rita G. Félix ◽

Pedro R.D. Simões ◽

Francisco J.P.M. Sousa ◽

M. Elisa Silva Serra ◽

Dina Murtinho

Keyword(s):

Reaction Time ◽

Aldol Reaction ◽

Aromatic Aldehydes ◽

Aldol Reactions ◽

Catalyst Loading ◽

Reaction Parameters ◽

Asymmetric Aldol ◽

Asymmetric Aldol Reaction

Several novel chiral organocatalysts derived from thiazolidines containing amide and thioureia functionalities were synthesized in good yields. These organocatalysts were tested in the asymmetric aldol reaction of acetone with p-nitrobenzaldehyde. Reaction parameters such as reaction time, catalyst loading and solvent were optimized. Products with conversions up to 84% and enantiomeric ratios (er) up to 84.5:15.5 (R:S) were obtained. The effect of several chiral and non-chiral additives on the reactivity and selectivity of the reaction was also evaluated. The reaction was extended to other aromatic aldehydes with the best organocatalyst and when p-bromobenzaldehyde was used, an er of 94.5:5.5 (R:S) was obtained.

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DFT investigation on Lewis base-catalyzed Lewis acid-mediated reactions: hypervalent silicon species as chiral organocatalysts in (direct) aldol reactions

New Journal of Chemistry ◽

10.1039/d0nj03976d ◽

2020 ◽

Vol 44 (44) ◽

pp. 19288-19293

Author(s):

Sergio Rossi ◽

Maurizio Benaglia ◽

Laura Maria Raimondi

Keyword(s):

Lewis Acid ◽

Aldol Reaction ◽

Aromatic Aldehydes ◽

Lewis Base ◽

Aldol Reactions ◽

Enol Ethers ◽

Silyl Enol Ethers ◽

Direct Aldol Reaction

The stereoselective organocatalytic addition of silyl enol ethers to aromatic aldehydes catalyzed by bisphosphoramides and the direct aldol reaction between ketones and aromatic aldehydes promoted by phosphinoxides in the presence of tetrachlorosilane were investigated by the DFT approach.

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Using NMR To Investigate Products of Aldol Reactions: Identifying Aldol Addition versus Condensation Products or Conjugate Addition Products from Crossed Aldol Reactions of Aromatic Aldehydes and Ketones

ACS Symposium Series - NMR Spectroscopy in the Undergraduate Curriculum ◽

10.1021/bk-2013-1128.ch007 ◽

2013 ◽

pp. 91-102 ◽

Cited By ~ 2

Author(s):

Nanette M. Wachter

Keyword(s):

Aromatic Aldehydes ◽

Conjugate Addition ◽

Aldol Reactions ◽

Condensation Products ◽

Aldehydes And Ketones ◽

Aldol Addition

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Design of Novel Hydrogen-Bonding Donor Organocatalysts and Their Application to Asymmetric Direct Aldol Reaction

Synlett ◽

10.1055/s-0036-1558971 ◽

2017 ◽

Vol 28 (11) ◽

pp. 1363-1367 ◽

Cited By ~ 7

Author(s):

Tsuyoshi Miura ◽

Hiroshi Akutsu ◽

Kosuke Nakashima ◽

Hikaru Yanai ◽

Akira Kotani ◽

...

Keyword(s):

Hydrogen Bonding ◽

Catalytic Activity ◽

Aldol Reaction ◽

Aromatic Aldehydes ◽

Aldol Reactions ◽

Catalytic Activities ◽

Asymmetric Catalytic ◽

Direct Aldol Reaction ◽

Double Hydrogen

Asymmetric catalytic activities of various organocatalysts bearing double hydrogen-bonding donor units showing different pK a values were examined for direct aldol reactions of cyclohexanone with aromatic aldehydes. Organocatalyst with motif exhibiting the highest acidity resulted in the corresponding aldol products with the highest enantioselectivity. A good correlation has been observed between the asymmetric catalytic activity for direct aldol reactions and acidities of double hydrogen-bonding donating units.

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A review of lignin hydrogen peroxide oxidation chemistry with emphasis on aromatic aldehydes and acids

Holzforschung ◽

10.1515/hf-2020-0165 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Ajinkya More ◽

Thomas Elder ◽

Zhihua Jiang

Keyword(s):

Hydrogen Peroxide ◽

Oxidative Degradation ◽

Reaction Medium ◽

Dicarboxylic Acids ◽

Aromatic Aldehydes ◽

Product Distribution ◽

Reaction Conditions ◽

Alkaline Conditions ◽

The Stability ◽

Oxidation Chemistry

Abstract This review discusses the main factors that govern the oxidation processes of lignins into aromatic aldehydes and acids using hydrogen peroxide. Aromatic aldehydes and acids are produced in the oxidative degradation of lignin whereas mono and dicarboxylic acids are the main products. The stability of hydrogen peroxide under the reaction conditions is an important factor that needs to be addressed for selectively improving the yield of aromatic aldehydes. Hydrogen peroxide in the presence of heavy metal ions readily decomposes, leading to minor degradation of lignin. This degradation results in quinones which are highly reactive towards peroxide. Under these reaction conditions, the pH of the reaction medium defines the reaction mechanism and the product distribution. Under acidic conditions, hydrogen peroxide reacts electrophilically with electron rich aromatic and olefinic structures at comparatively higher temperatures. In contrast, under alkaline conditions it reacts nucleophilically with electron deficient carbonyl and conjugated carbonyl structures in lignin. The reaction pattern in the oxidation of lignin usually involves cleavage of the aromatic ring, the aliphatic side chain or other linkages which will be discussed in this review.

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