Marcos Escolano - Academia.edu (original) (raw)
Papers by Marcos Escolano
Journal of Organic Chemistry, Mar 15, 2022
The preparation of nonanomeric C-acyl-saccharides has been developed from two different carboxyli... more The preparation of nonanomeric C-acyl-saccharides has been developed from two different carboxylic acid feedstocks. This transformation is driven by the synergistic interaction of an electron donor-acceptor complex and Ni catalysis. Primary-, secondary-, and tertiary redox-active esters are incorporated as coupling partners onto preactivated pyranosyl- and furanosyl acids, preserving their stereochemical integrity. The reaction occurs under mild conditions, without stoichiometric metal reductants or exogenous catalysts, using commercially available Hantzsch ester as the organic photoreductant.
Organic chemistry frontiers, 2019
The total synthesis of (+)-anaferine and (−)-dihydrocuscohygrine is described. Bidirectional cros... more The total synthesis of (+)-anaferine and (−)-dihydrocuscohygrine is described. Bidirectional cross metathesis/double intramolecular aza-Michael reactions were the key steps.
Organic Letters, May 1, 2023
Chemical Record, Aug 20, 2021
The asymmetric intramolecular aza‐Michael reaction (IMAMR) is a very convenient strategy for the ... more The asymmetric intramolecular aza‐Michael reaction (IMAMR) is a very convenient strategy for the generation of heterocycles bearing nitrogen‐substituted stereocenters. Due to the ubiquitous presence of these skeletons in natural products, the IMAMR has found widespread applications in the total synthesis of alkaloids and biologically relevant compounds. The development of asymmetric versions of the IMAMR are quite recent, most of them reported in this century. The fundamental advances in this field involve the use of organocatalysts. Chiral imidazolidinones, diaryl prolinol derivatives, Cinchone‐derived primary amines and quaternary ammonium salts, and BINOL‐derived phosphoric acids account for the success of those methodologies. Moreover, the use of N‐sulfinyl imines with a dual role, as nitrogen nucleophiles and as chiral auxiliaries, appeared as a versatile mode of performing the asymmetric IMAMR.
Organic and Biomolecular Chemistry, 2018
Synthesis of N-protected diolefinic amines 1, 2 General procedure for the CM reaction: synthesis ... more Synthesis of N-protected diolefinic amines 1, 2 General procedure for the CM reaction: synthesis of symmetrical bis-enones 3, 4 General procedure for the IMAMR: synthesis of disubstituted piperidines 5, 6 Synthesis of 2,5-disubstituted piperidine 9 for the X-ray analysis X-Ray structure of compound 9 Stereochemical assignment of 2,6-disubstituted piperidines 6 Computational study HPLC traces of enantioenriched piperidines 5 and 6 NMR spectra of new compounds Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.
Chem catalysis, Apr 1, 2022
Journal of Organic Chemistry, Feb 20, 2017
The intramolecular 1,3-dipolar cycloaddition of ortho-substituted 1,1,1-trifluoromethyl styrenede... more The intramolecular 1,3-dipolar cycloaddition of ortho-substituted 1,1,1-trifluoromethyl styrenederived nitrones is described. Tricyclic fused isoxazolidines were obtained as major or exclusive products, in contrast to non-fluorinated substrates, which rendered the bridged derivatives. This change in the regioselectivity was attributed to the electronic and, particularly, steric requirements of the trifluoromethyl group when compared to the methyl group. It is worth mentioning that trifluoromethyl styrenes have been employed for the first time as dipolarophiles in a 1,3-dipolar intramolecular cycloaddition reaction, leading to the corresponding isoxazolidines bearing a quaternary trifluoromethyl moiety. Finally, the synthetic utility of the
Advanced Synthesis & Catalysis, Jan 23, 2019
European Journal of Organic Chemistry, Jun 1, 2021
An unprecedented enantioselective intramolecular oxa-Michael reaction of enols has been described... more An unprecedented enantioselective intramolecular oxa-Michael reaction of enols has been described. A squaramide containing tertiary amine based bifunctional organocatalyst is efficiently activating the ortho-homoformyl chalcones to provide the chiral isochromenes in moderate yields and good to excellent enantioselectivities. Further, late stage functionalizations of vinyl-ether moiety of the chiral isochromene products have also been exemplified.
Chemical Communications, 2020
Hydroxycarboxylic acids (ether carboxylic acids) and esters P 0280 Organocatalytic Enantioselecti... more Hydroxycarboxylic acids (ether carboxylic acids) and esters P 0280 Organocatalytic Enantioselective Synthesis of Secondary α-Hydroxycarboxylates.-A novel L-proline-derived dipeptide PDP is found to be highly efficient for the aldol reaction of ethyl glyoxylate and ketones.-(DODDA, R.; ZHAO*, C.-G.
Advanced Synthesis & Catalysis, May 3, 2021
A highly enantioselective Friedel−Crafts reaction of pyrrole derivatives with N-acyl imines catal... more A highly enantioselective Friedel−Crafts reaction of pyrrole derivatives with N-acyl imines catalyzed by chiral phosphoric acids was developed. The reactions produced the pyrrole derivatives in high yields and enantioselectivity. The Friedel-Crafts reaction is undoubtedly one of the most important carbon-carbon bond forming reactions in organic synthesis. 1 In recent years the asymmetric Friedel-Crafts reaction has attracted considerable interest among academics. An important aspect of enantioselective variants to this reaction is the resulting abillity to synthesize enantiopure arenes, which are desired synthetic intermediates and biologically active compounds. 2 Recently, there have been several reports of asymmetric Friedel-Crafts reactions of indole derivatives with both organocatalytic and metalcatalyzed systems. 3 However, pyrroles are also important heterocycles that are often found in natural products and drug candidates that could potentially be accessed by asymmetric Friedel-Crafts chemistry. 4 Methodologies for the asymmetric Friedel-Crafts reaction of pyrroles are very limited. The first example of a highly enantioselective Friedel-Crafts reaction of pyrrole was reported by MacMillan in 2001 using a chiral imidizolidinone catalyst. 5 Chiral Lewis acid complexes have also been demonstrated to be excellent catalysts for the enantioselective Friedel-Crafts reaction of pyrrole derivatives with R,-unsturated systems. 6 Organocatalytic enantioselective synthesis has witnessed rapid development in the past years owing to its potential
Organic Letters, Nov 30, 2020
A triple-tandem protocol for the synthesis of the pyrrolizidinone skeleton has been devised. It i... more A triple-tandem protocol for the synthesis of the pyrrolizidinone skeleton has been devised. It involves a cross metathesis−intramolecular aza-Michael reaction−intramolecular Michael addition tandem sequence, starting from N-pentenyl-4oxo-2-alkenamides and conjugated ketones. In the presence of two cooperative catalysts, namely the second-generation Hoveyda− Grubbs catalyst and (R)-TRIP-derived BINOL phosphoric acid, this multiple-relay catalytic process takes place in good yields and outstanding levels of diastero-and enantioselectivity with the simultaneous generation of three contiguous stereocenters
Advanced Synthesis & Catalysis, Jun 14, 2018
Pharmaceuticals
The interest in 3,4-dihydropyrimidine-2(1H)-(thio)ones is increasing every day, mainly due to the... more The interest in 3,4-dihydropyrimidine-2(1H)-(thio)ones is increasing every day, mainly due to their paramount biological relevance. The Biginelli reaction is the classical approach to reaching these scaffolds, although the product diversity suffers from some limitations. In order to overcome these restrictions, two main approaches have been devised. The first one involves the modification of the conventional components of the Biginelli reaction and the second one refers to the postmodification of the Biginelli products. Both strategies have been extensively revised in this manuscript. Regarding the first one, initially, the modification of one of the components was covered. Although examples of modifications of the three of them were described, by far the modification of the keto ester counterpart was the most popular approach, and a wide variety of different enolizable carbonylic compounds were used; moreover, changes in two or the three components were also described, broadening t...
Advanced Synthesis & Catalysis
The asymmetric synthesis of tetracyclic pyrroles bearing a tetrasubstituted carbon stereocenter h... more The asymmetric synthesis of tetracyclic pyrroles bearing a tetrasubstituted carbon stereocenter has been accomplished through a one‐pot sequence that comprises a cross metathesis reaction followed by a tandem cycloisomerization/ intramolecular Pictet‐Spengler‐type reaction. This sequence took place on conveniently functionalized chiral amino acids to render the final products in good overall yields and diastereoselectivities up to 20:1. Those pyrrole‐containing scaffolds are present in a variety of biologically relevant compounds.magnified image
The Journal of Organic Chemistry, 2022
The preparation of nonanomeric C-acyl-saccharides has been developed from two different carboxyli... more The preparation of nonanomeric C-acyl-saccharides has been developed from two different carboxylic acid feedstocks. This transformation is driven by the synergistic interaction of an electron donor-acceptor complex and Ni catalysis. Primary-, secondary-, and tertiary redox-active esters are incorporated as coupling partners onto preactivated pyranosyl- and furanosyl acids, preserving their stereochemical integrity. The reaction occurs under mild conditions, without stoichiometric metal reductants or exogenous catalysts, using commercially available Hantzsch ester as the organic photoreductant.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Journal of Organic Chemistry, Mar 15, 2022
The preparation of nonanomeric C-acyl-saccharides has been developed from two different carboxyli... more The preparation of nonanomeric C-acyl-saccharides has been developed from two different carboxylic acid feedstocks. This transformation is driven by the synergistic interaction of an electron donor-acceptor complex and Ni catalysis. Primary-, secondary-, and tertiary redox-active esters are incorporated as coupling partners onto preactivated pyranosyl- and furanosyl acids, preserving their stereochemical integrity. The reaction occurs under mild conditions, without stoichiometric metal reductants or exogenous catalysts, using commercially available Hantzsch ester as the organic photoreductant.
Organic chemistry frontiers, 2019
The total synthesis of (+)-anaferine and (−)-dihydrocuscohygrine is described. Bidirectional cros... more The total synthesis of (+)-anaferine and (−)-dihydrocuscohygrine is described. Bidirectional cross metathesis/double intramolecular aza-Michael reactions were the key steps.
Organic Letters, May 1, 2023
Chemical Record, Aug 20, 2021
The asymmetric intramolecular aza‐Michael reaction (IMAMR) is a very convenient strategy for the ... more The asymmetric intramolecular aza‐Michael reaction (IMAMR) is a very convenient strategy for the generation of heterocycles bearing nitrogen‐substituted stereocenters. Due to the ubiquitous presence of these skeletons in natural products, the IMAMR has found widespread applications in the total synthesis of alkaloids and biologically relevant compounds. The development of asymmetric versions of the IMAMR are quite recent, most of them reported in this century. The fundamental advances in this field involve the use of organocatalysts. Chiral imidazolidinones, diaryl prolinol derivatives, Cinchone‐derived primary amines and quaternary ammonium salts, and BINOL‐derived phosphoric acids account for the success of those methodologies. Moreover, the use of N‐sulfinyl imines with a dual role, as nitrogen nucleophiles and as chiral auxiliaries, appeared as a versatile mode of performing the asymmetric IMAMR.
Organic and Biomolecular Chemistry, 2018
Synthesis of N-protected diolefinic amines 1, 2 General procedure for the CM reaction: synthesis ... more Synthesis of N-protected diolefinic amines 1, 2 General procedure for the CM reaction: synthesis of symmetrical bis-enones 3, 4 General procedure for the IMAMR: synthesis of disubstituted piperidines 5, 6 Synthesis of 2,5-disubstituted piperidine 9 for the X-ray analysis X-Ray structure of compound 9 Stereochemical assignment of 2,6-disubstituted piperidines 6 Computational study HPLC traces of enantioenriched piperidines 5 and 6 NMR spectra of new compounds Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.
Chem catalysis, Apr 1, 2022
Journal of Organic Chemistry, Feb 20, 2017
The intramolecular 1,3-dipolar cycloaddition of ortho-substituted 1,1,1-trifluoromethyl styrenede... more The intramolecular 1,3-dipolar cycloaddition of ortho-substituted 1,1,1-trifluoromethyl styrenederived nitrones is described. Tricyclic fused isoxazolidines were obtained as major or exclusive products, in contrast to non-fluorinated substrates, which rendered the bridged derivatives. This change in the regioselectivity was attributed to the electronic and, particularly, steric requirements of the trifluoromethyl group when compared to the methyl group. It is worth mentioning that trifluoromethyl styrenes have been employed for the first time as dipolarophiles in a 1,3-dipolar intramolecular cycloaddition reaction, leading to the corresponding isoxazolidines bearing a quaternary trifluoromethyl moiety. Finally, the synthetic utility of the
Advanced Synthesis & Catalysis, Jan 23, 2019
European Journal of Organic Chemistry, Jun 1, 2021
An unprecedented enantioselective intramolecular oxa-Michael reaction of enols has been described... more An unprecedented enantioselective intramolecular oxa-Michael reaction of enols has been described. A squaramide containing tertiary amine based bifunctional organocatalyst is efficiently activating the ortho-homoformyl chalcones to provide the chiral isochromenes in moderate yields and good to excellent enantioselectivities. Further, late stage functionalizations of vinyl-ether moiety of the chiral isochromene products have also been exemplified.
Chemical Communications, 2020
Hydroxycarboxylic acids (ether carboxylic acids) and esters P 0280 Organocatalytic Enantioselecti... more Hydroxycarboxylic acids (ether carboxylic acids) and esters P 0280 Organocatalytic Enantioselective Synthesis of Secondary α-Hydroxycarboxylates.-A novel L-proline-derived dipeptide PDP is found to be highly efficient for the aldol reaction of ethyl glyoxylate and ketones.-(DODDA, R.; ZHAO*, C.-G.
Advanced Synthesis & Catalysis, May 3, 2021
A highly enantioselective Friedel−Crafts reaction of pyrrole derivatives with N-acyl imines catal... more A highly enantioselective Friedel−Crafts reaction of pyrrole derivatives with N-acyl imines catalyzed by chiral phosphoric acids was developed. The reactions produced the pyrrole derivatives in high yields and enantioselectivity. The Friedel-Crafts reaction is undoubtedly one of the most important carbon-carbon bond forming reactions in organic synthesis. 1 In recent years the asymmetric Friedel-Crafts reaction has attracted considerable interest among academics. An important aspect of enantioselective variants to this reaction is the resulting abillity to synthesize enantiopure arenes, which are desired synthetic intermediates and biologically active compounds. 2 Recently, there have been several reports of asymmetric Friedel-Crafts reactions of indole derivatives with both organocatalytic and metalcatalyzed systems. 3 However, pyrroles are also important heterocycles that are often found in natural products and drug candidates that could potentially be accessed by asymmetric Friedel-Crafts chemistry. 4 Methodologies for the asymmetric Friedel-Crafts reaction of pyrroles are very limited. The first example of a highly enantioselective Friedel-Crafts reaction of pyrrole was reported by MacMillan in 2001 using a chiral imidizolidinone catalyst. 5 Chiral Lewis acid complexes have also been demonstrated to be excellent catalysts for the enantioselective Friedel-Crafts reaction of pyrrole derivatives with R,-unsturated systems. 6 Organocatalytic enantioselective synthesis has witnessed rapid development in the past years owing to its potential
Organic Letters, Nov 30, 2020
A triple-tandem protocol for the synthesis of the pyrrolizidinone skeleton has been devised. It i... more A triple-tandem protocol for the synthesis of the pyrrolizidinone skeleton has been devised. It involves a cross metathesis−intramolecular aza-Michael reaction−intramolecular Michael addition tandem sequence, starting from N-pentenyl-4oxo-2-alkenamides and conjugated ketones. In the presence of two cooperative catalysts, namely the second-generation Hoveyda− Grubbs catalyst and (R)-TRIP-derived BINOL phosphoric acid, this multiple-relay catalytic process takes place in good yields and outstanding levels of diastero-and enantioselectivity with the simultaneous generation of three contiguous stereocenters
Advanced Synthesis & Catalysis, Jun 14, 2018
Pharmaceuticals
The interest in 3,4-dihydropyrimidine-2(1H)-(thio)ones is increasing every day, mainly due to the... more The interest in 3,4-dihydropyrimidine-2(1H)-(thio)ones is increasing every day, mainly due to their paramount biological relevance. The Biginelli reaction is the classical approach to reaching these scaffolds, although the product diversity suffers from some limitations. In order to overcome these restrictions, two main approaches have been devised. The first one involves the modification of the conventional components of the Biginelli reaction and the second one refers to the postmodification of the Biginelli products. Both strategies have been extensively revised in this manuscript. Regarding the first one, initially, the modification of one of the components was covered. Although examples of modifications of the three of them were described, by far the modification of the keto ester counterpart was the most popular approach, and a wide variety of different enolizable carbonylic compounds were used; moreover, changes in two or the three components were also described, broadening t...
Advanced Synthesis & Catalysis
The asymmetric synthesis of tetracyclic pyrroles bearing a tetrasubstituted carbon stereocenter h... more The asymmetric synthesis of tetracyclic pyrroles bearing a tetrasubstituted carbon stereocenter has been accomplished through a one‐pot sequence that comprises a cross metathesis reaction followed by a tandem cycloisomerization/ intramolecular Pictet‐Spengler‐type reaction. This sequence took place on conveniently functionalized chiral amino acids to render the final products in good overall yields and diastereoselectivities up to 20:1. Those pyrrole‐containing scaffolds are present in a variety of biologically relevant compounds.magnified image
The Journal of Organic Chemistry, 2022
The preparation of nonanomeric C-acyl-saccharides has been developed from two different carboxyli... more The preparation of nonanomeric C-acyl-saccharides has been developed from two different carboxylic acid feedstocks. This transformation is driven by the synergistic interaction of an electron donor-acceptor complex and Ni catalysis. Primary-, secondary-, and tertiary redox-active esters are incorporated as coupling partners onto preactivated pyranosyl- and furanosyl acids, preserving their stereochemical integrity. The reaction occurs under mild conditions, without stoichiometric metal reductants or exogenous catalysts, using commercially available Hantzsch ester as the organic photoreductant.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.