169,996 research outputs found
The CeCl3 Lewis Acid Promoter in the Stereoselective Construction of Carbon-Carbon Double Bonds
No full textThe presence of a C-C double bond in polyfunctionalized organic molecules is a crucial requirement
for the control of its biologically activity.(1) The importance of having a site in the molecule that is
able to generate geometrical isomerization of a carbon-carbon double bond stimulated the
development of new olefination methodologies. In particular, some efforts focused on the ability of
Lewis acids to provide a cheap alternative for the synthesis of molecules with C-C double bond in a
highly stereoselective fashion.
For several years, we have been investigating CeCl3 promoted organic reactions. This Lewis acid has
been found to efficiently promote carbon-carbon (2) and carbon-heteroatom bond formation
reactions.(3) In addition to being green in nature (4), CeCl3 has been widely used for both inter- and
intramolecular reactions for the synthesis of organic molecules with significant biological
importance.
Regarding the total synthesis of biologically active small molecules containing a carbon-carbon
double bond, we saw the possibility to employ CeCl3 in the stereoselective construction of 2,3-
dihydropyridones 1,(5) and 1,2-dihydroquinolines 2.(6)
The additional advantage of using CeCl3 in a reaction includes its selectivity and tolerance in the
presence of other functional groups. For instance, it can be used during the functionalization of
molecules at late stage involving complex molecules or undesirable use of protecting groups.
Introduction of C-C double bonds, which are known to increase the activity in macrolides against
bacterial RNA polymerase, is currently in progress in our laboratory.
References: 1. Shen, X.; Nguyen, T. T.; Koh, M. J.; Xu, D.; Speed, A. W.; Schrock, R. R.; Hoveyda, A. H. Nature 2017,
541, 380-385. 2. Bartoli, G.; Marcolin, M.; Sambri, L.; Marcantoni, E. Chem. Rev. 2010, 110, 6104-6143. 3. Properzi, R.
Marcantoni, E. Chem. Soc. Rev. 2014, 43, 779-791. 4. Cimarelli, C.; Di Nicola, M.; Diomedi, S.; Giovannini, R.;
Hanprecht, D.; Properzi, R.; Sorana, F.; Marcantoni, E. Org. Biomol. Chem. 2015, 13, 11687-11695. 5. Bordi, S.;
Cimarelli, C.; Lupidi, G.; Marsili, L.; Piermattei, P.; Marcantoni, E. J. Org. Chem. 2017, in preparation. 6. Cimarelli, C.;
Bordi, S.; Piermattei, P.; Pellei, M.; Del Bello, F.; Marcantoni, E. Tetrahedron 2017, submitted
The A3 Coupling Reactions Catalyzed by Efficient Lewis Acid Systems
No full textPropargylamines belong to a widely studied1 class of building blocks because of their
particular molecular skeleton that contains an amine group, suitable for nucleophilic reactions, located
in E-position to an alkyne moiety, that can act both as an electrophile and as a source of electrons in
nucleophilic reactions.2
Our goal was the development of green and simple Lewis acid catalyzed methodologies to
the A3 reaction for the synthesis of primary propargylamines from aldehydes, primary amines and
alkynes. In particular, we applied two different Lewis acid catalysts to this reaction: the CuSO4/NaI
system in one pot fashion and the CeCl3/CuI system in one pot/two steps way.
Figure 1 – CeCl3·7H2O/CuI and CuSO4/NaI catalyzed A3 reaction. Reaction conditions:
i) MgSO4, CeCl3·7H2O 30% mol, solventless, N2, r.t., 0.25h.
ii) CuI 30% mol, solventless, N2, 40°C
iii) CuSO4 30% mol/NaI 60% mol, PhCOOH 5% mol, solventless, N2, 80°C
Heptahydrated CeCl3 is a very good catalyst for the formation of imines, widely used also in
the synthesis of several classes of organic compounds.3 Its efficacy is enhanced in the presence of
inorganic iodides4 and being copper the transition metal of choice for A3 reactions, CuI was used.
Also the CuSO4/NaI couple has revealed to be an interesting Lewis acid system, alternative
to CeCl3/CuI system. The reaction has been applied also to chiral starting materials and, in general,
the amine has no effect on the reaction outcome. Typically CuSO4/NaI catalysed reactions are faster,
but suffer of some disadvantages, such as lower yields, and a narrower applicability. The relevant
Glaser coupling drawback observed in these conditions has been suppressed by adding some benzoic
acid, and has not been observed with the CeCl3/CuI system.
References:
[1] K. Lauder, A. Toscani, N. Scalacci, D. Castagnolo Chem. Rev. 2017, 117, 14091 – 1420.
[2] V. A. Peshkov, O. P. Pereshivko, E. V. Van der Eycken Chem. Soc. Rev. 2012, 41, 3790 – 3807.
[3] R. Properzi, E. Marcantoni Chem. Soc. Rev., 2014, 43, 779 - 791.
[4] G. Bartoli, E. Marcantoni, M. Marcolini, L. Sambri Chem. Rev. 2010, 110, 6104 – 6143
Efficient Lewis Acid Systems for the A3 Coupling reaction
No full textEfficient Lewis Acid Systems for the A3 Coupling reaction
Cimarelli C., a Navazio F.,a Rossi F. V.a, Del Bello F., Marcantoni E.a
aSchool of Science and Technology, Chemistry Division, University of Camerino, Via S. Agostino 1, 62032 Camerino; e-mail: [email protected]
Propargylamines are an attractive class of molecules because of their particular molecular skeleton, that contains an amine group located in β-position to an alkyne moiety suitable for many chemical transformations. In recent years they received a growing interest as key intermediates for several biologically active compound, natural products and also different heterocycles.[1,2]
Our goal was the development of green and simple methodologies for the synthesis of secondary propargylamines by Lewis acid catalyzed or promoted A3 reaction among aldehydes, alkynes and primary amines, that are in general less applied in such reactions because of their lower reactivity. In particular, we studied two different pathway: the CuSO4/NaI system in one pot fashion and the CeCl3/CuI system in one pot/two steps way (Scheme 1).
Scheme 1. CeCl3·7H2O/CuI and CuSO4/NaI catalyzed A3 reaction.
Heptahydrated CeCl3 is reported to be an excellent catalyst for many useful organic transformation as the synthesis of imines. Its efficacy as Lewis acid is enhanced in the presence of inorganic iodides/iodide salt and being cooper the transition metal of choice for A3 reactions, CuI was used.[3]
Also the CuSO4/NaI couple has revealed to be an interesting Lewis acid system as an alternative to CeCl3/CuI system which allow the formation of CuI in situ by quantitative spontaneous reaction that takes place in few seconds.[4]
Typically CuSO4/NaI catalysed reactions are faster than CeCl3·7H2O/CuI reactions, but suffer of some disadvantages, such as lower yields, and a narrower applicability. Both reaction conditions have been applied to different aldehydes (aromatic and aliphatic) and to chiral starting materials, the amine in general has no effect on the reaction outcome.
The relevant Glaser coupling drawback observed in the CuSO4/NaI system conditions has been suppressed by adding some benzoic acid, and has not been observed with the CeCl3/CuI system.
References:
1) Lauder, K.; Toscani, A.; Scalacci, N.; Castagnolo, D. Chem. Rev. 2017, 117, 14091.
2) Peshkov, V. A.; Pereshivko, O. P.; Van der Eycken, E. V. Chem. Soc. Rev. 2012, 41, 3790.
3) G. Bartoli, E. Marcantoni, M. Marcolini, L. Sambri, Chem. Rev. 2010, 110, 6104.
4) Bailey, A. D.; Cherney, S. M.; Anzalone, P. W.; Anderson, E. D.; Ernat, J. J.; Mohan, R. S. Synlett 2006, 215
Thermodynamics of a qubit undergoing dephasing
No full textThe thermodynamics of a qubit undergoing dephasing due to the coupling with the external environment is discussed. First of all, we assume the dynamics of the system to be described by a master equation in Lindblad form. In this framework, we review a standard formulation of the first and second law of thermodynamics that has been known in literature for a long time. After that, we explicitly model the environment with a set of quantum harmonic oscillators choosing the interaction such that the global dynamics of system and bath is analytically solvable and the Lindblad master equation is recovered in the weak-coupling limit. In this generalized setting, we can show that the correlations between system and bath play a fundamental role in the heat exchange. Moreover, the internal entropy production of the qubit is proven to be positive for arbitrary coupling strength
CeCl3 catalyzed imino Diels-Alder reactions: hydrated vs anhydrous
No full textAza-Diels-Alder reaction is a straightforward way to synthesize useful nitrogen containing heterocyclic structures.1 In particular, the known reaction between imines and Danishefsky’s diene has proved to be an excellent way to obtain the 1,2-substituted-2,3-dihydropyridinone scaffold, widely present in bioactive small molecules and versatile building block for the synthesis of more complex structures.2
The reaction of Danishefsky’s diene with aromatic imines has been widely studied in last years, anyway less examples of the same reaction involving imines derived from aliphatic amines or aldehydes are present. For this reason the possibility to extend the potentiality of this reaction performing it on a large variety of imines was studied, under the Lewis acid promoting system CeCl3.7H2O/CuI, previously applied with success3 in many other synthetic methodologies.
Imines 3 were prepared by direct condensation of aliphatic or aromatic amines and aldehydes and then the diene was added together with the catalyst, obtaining dihydropyridinones 4 with good to excellent yields in short reaction times. To extend the scope of this work, also imines derived from aminoacids were tested as dienophiles.
The only moderate diastereoselectivity and the long time needed with some homochiral dienophiles prompted us to have a deeper insight into the mechanism, with the conclusion that the reaction proceed also through a slower competitive Mannich-Michael pathway, favoured by the presence of water in the catalyst.
1) Buonora, P.; Olsen, J.-C.; Oh, T. Tetrahedron 2001, 57, 6099-6138.
2) Cant, A. A.; Sutherland, A. Synthesis 2012, 44, 1935-1950.
3) Bartoli, G.; Marcantoni, E.; Marcolini, M.; Sambri, L. Chem. Rev. 2010, 110, 6104-6143
Lewis Acid Promoted Addition Reactions of Organometallic Compounds
No full textDuring recent years, great achievements have been made in the field of organometallic chemistry, for which several Nobel Prizes in Chemistry have been awarded. Organometallic chemistry has the potential to combine excellent selectivity and reactivity with low cost, environmental friendliness, and high functional group tolerance. The reactivity of organometallics strongly depends on the character of
the metal – carbon, and the addition of nonstabilized organometallic reagents to carbon electrophiles has gained considerable importance in organic synthesis. For organic chemists the Lewis acids are an extremely useful tool that plays substantial roles in overcoming the lack of selectivity in several additions of organometallic compounds. In this chapter of Volume 1 of Comprehensive Organic Synthesis 2nd edition we will take into consideration the ability of Lewis acids to coordinate C=X bonds ( for X=oxygen or
nitrogen) and favoring additions of organometallic nucleophiles, and how these can be exploited in organic synthesis
C-alpha' and C-beta' alkylation of ketones via alpha-nitro ketones: A new synthesis of (+-)4-methyl-3-heptanone, (+-)-Phoracantholide, (+-)-Dihydrorecifeiolide, and (+-)-Muscone.
No full textClassification of drug-induced hERG potassium-channel block from electrocardiographic T-wave features using artificial neural networks
No full textBackground: Human ether‐à‐go‐go‐related gene (hERG) potassium‐channel block
represents a harmful side effect of drug therapy that may cause torsade de pointes
(TdP). Analysis of ventricular repolarization through electrocardiographic T‐wave features
represents a noninvasive way to accurately evaluate the TdP risk in drug‐safety
studies. This study proposes an artificial neural network (ANN) for noninvasive electrocardiography‐
based classification of the hERG potassium‐channel block.
Methods: The data were taken from the “ECG Effects of Ranolazine, Dofetilide,
Verapamil, and Quinidine in Healthy Subjects” Physionet database; they consisted of
median vector magnitude (VM) beats of 22 healthy subjects receiving a single 500 μg
dose of dofetilide. Fourteen VM beats were considered for each subject, relative
to time‐points ranging from 0.5 hr before to 14.0 hr after dofetilide administration.
For each VM, changes in two indexes accounting for the early and the late phases
of repolarization, ΔERD30% and ΔTS/A, respectively, were computed as difference
between values at each postdose time‐point and the predose time‐point. Thus, the
dataset contained 286 ΔERD30%‐ΔTS/A pairs, partitioned into training, validation, and
test sets (114, 29, and 143 pairs, respectively) and used as inputs of a two‐layer feedforward
ANN with two target classes: high block (HB) and low block (LB). Optimal
ANN (OANN) was identified using the training and validation sets and tested on the
test set.
Results: Test set area under the receiver operating characteristic was 0.91; sensitivity,
specificity, accuracy, and precision were 0.93, 0.83, 0.92, and 0.96, respectively.
Conclusion: OANN represents a reliable tool for noninvasive assessment of the hERG
potassium‐channel block
[Hypertensive nephrosclerosis: an exhaustive diagnosis?].
No full textHypertensive nephrosclerosis is a much overused clinical diagnosis, largely unsubstantiated by biopsy data. It is in fact a clinical-pathological diagnosis implying a causal role of hypertension in the associated chronic kidney disease. However, such a simple, linear causality is often not obvious or easy to demonstrate. Further factors like age, Afro-American descent, genetic and immunological factors as well as dysmetabolic syndrome may contribute to the development and progression of arterionephrosclerosis independently of hypertension
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