scholarly journals Chiral Thioureas Promote Enantioselective Pictet–Spengler Cyclization by Stabilizing Every Intermediate and Transition State in the Carboxylic Acid-Catalyzed Reaction

2017 ◽  
Vol 139 (35) ◽  
pp. 12299-12309 ◽  
Author(s):  
Rebekka S. Klausen ◽  
C. Rose Kennedy ◽  
Alan M. Hyde ◽  
Eric N. Jacobsen
Keyword(s):  
Carboxylic Acid ◽  
Transition State ◽  
Acid Catalyzed

General acid-catalyzed addition of methanol to (E)-N-benzylideneanilines

1999 ◽  
Vol 77 (5-6) ◽  
pp. 760-773 ◽  
Author(s):  
Sadjia Bennour ◽  
Jean Toullec
Keyword(s):  
Carboxylic Acid ◽  
Transition State ◽  
Rate Constants ◽  
Bond Cleavage ◽  
Substituent Effects ◽  
Bond Forming ◽  
General Acid ◽  
Acid Catalyzed ◽  
Catalytic Rate ◽  
Solvent Molecules

The reaction of equilibrium addition of methanol (α-amino ether formation) to benzylideneanilines (C6H5=NC6H4Y, with Y = H (1a), 3-Cl (1b), 3-NO2 (1c), 4-CN (1d), and 4-NO2(1e)) in methanol is shown to be general acid-catalyzed in carboxylic acid buffers. The mechanism involves fast iminium ion formation followed by base-assisted addition of methanol. The α Brønsted exponents are in the 0.67-0.88 range, and α increases with the electron-withdrawing ability of Y. The same mechanism is valid for MeOH2+-catalysis, meaning that two solvent molecules are involved in the addition process, one of them playing the role of base. The equilibrium constant, K, is increased by electron-withdrawing substituents, log K depending linearly on the σ- substituent parameters. The substituent effects on the forward and reverse catalytic rate constants are analyzed by means of the log k = ρnσn + ρr(σ- - σn) + constant (Young-Jencks) equation. For carboxylic acid catalysis, the ρn and ρr parameters are in keeping with ca. half C—O bond forming or breaking at the transition state. The catalytic rate constants and α exponent for elimination of ClCH2CH2OH in methanol from the C6H5CH(OCH2CH2Cl)NH(4-CNC6H4) chloroethyl adduct are compared with those for the elimination of methanol from C6H5CH(OCH3)NH(4-CNC6H4). The chloromethyl group makes the reaction slower and α lower. This indicates that proton transfer is a little ahead of C—O bond cleavage at the transition state. Y substituent effects, α values, and the effects of the CH2Cl group are interpreted on the basis of a More O'Ferrall - Jencks diagram.Key words: imine, free energy linear relationship, nucleophilic addition, More O'Ferrall - Jencks diagram, Schiff base

Trifluoroacetic acid catalyzed highly regioselective bromocyclization of styrene-type carboxylic acid

2016 ◽  
Vol 14 (20) ◽  
pp. 4571-4575 ◽  
Author(s):  
Tao Chen ◽  
Ying-Yeung Yeung
Keyword(s):  
Carboxylic Acid ◽  
Trifluoroacetic Acid ◽  
Acid Catalyzed

A trifluoroacetic acid catalyzed highly 6-endo regioselective bromocyclization of styrene-type carboxylic acid has been developed.

The Theodorakis Synthesis of (–)-Jiadifenolide

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Hydrogen Peroxide ◽  
Carboxylic Acid ◽  
Aldol Condensation ◽  
University Of California ◽  
Oxidative Rearrangement ◽  
Promote Neurite Outgrowth ◽  
Starting Point ◽  
Jones Reagent ◽  
Acid Catalyzed ◽  
The University

There has recently been a great deal of interest in the synthesis of natural products that promote neurite outgrowth. Emmanuel A. Theodorakis of the University of California, San Diego described (Angew. Chem. Int. Ed. 2011, 50, 3672) the preparation of one of the most potent (10 nM) of these, (–)-jiadifenolide 3. Fittingly, a key transformation en route to this highly oxygenated seco-prezizaane was the oxidative rearrangement of 1 to 2. The starting point for the synthesis was the commercially available diketone 4. Allylation followed by addition to 5 gave the prochiral triketone 6. Enantioselective aldol condensation following the Tu/Zhang protocol then delivered the bicyclic enone 7. Alkylation to give 8 proceeded with high diastereoselectivity, perhaps controlled by the steric bulk of the silyloxy group. Exposure of the protected ketone to the McMurry reagent PhNTf2 gave the enol triflate 9, which smoothly carbonylated to the lactone 10. Epoxidation with alkaline hydrogen peroxide followed by oxidation gave the carboxylic acid, which spontaneously opened the epoxide, leading to the bis lactone 1. With 1 in hand, the stage was set for the key oxidative rearrangement to 2. It was envisioned that epoxidation would generate the cis-fused 11, which on oxidation would undergo acid-catalyzed elimination to give 12. The newly freed OH would then be in position to engage the lactone carbonyl, leading to 2. In the event, oxidation of the epoxide with the Dess-Martin reagent required sonication for 2 h. The rearranged lactone, even though it was susceptible to further oxidation, was secured in 38% overall yield from 1. After hydrogenation and protection, preparation of the enol triflate 13 from the congested cyclopentanone necessitated the use of the more reactive Comins reagent. Hydrogenation of the trisubstituted alkene from coupling with Me3Al then required 90 atmospheres of H2 overpressure. Hydroxylation of the lactone 14 with the Davis oxaziridine followed by further oxidation to the ketone with the Jones reagent and deprotection then completed the synthesis of (–)-jiadifenolide 3.

Dehydrogenation of Alcohols to Carboxylic Acid Catalyzed by in Situ-Generated Facial Ruthenium-CPP Complex

2019 ◽  
Vol 84 (14) ◽  
pp. 9151-9160 ◽  
Author(s):  
Hui-Min Liu ◽  
Lei Jian ◽  
Chao Li ◽  
Chun-Chun Zhang ◽  
Hai-Yan Fu ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Acid Catalyzed
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