Melvin De Jesús | University of Puerto Rico - Humacao (original) (raw)

Papers by Melvin De Jesús

Journal of Organic Chemistry, Oct 28, 2005

[reaction: see text] Aromatic O-triisopropylsilyl ketoximes were efficiently rearranged to cyclic... more [reaction: see text] Aromatic O-triisopropylsilyl ketoximes were efficiently rearranged to cyclic and acyclic aniline derivatives on reduction with BF3-ethearate/borane. The bulk of the substituents on the silicon atom, the size of the aliphatic ring, and the presence of alkoxy substituents on the aryl group all play an important role in the aniline.

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.

The Journal of Organic Chemistry, 2008

A practical and efficient procedure for the enantioselective synthesis of mexiletine analogues wi... more A practical and efficient procedure for the enantioselective synthesis of mexiletine analogues with use of 10% of spiroborate ester 6 as chirality transfer agent is presented. A variety of mexiletine analogues were prepared in good yield with excellent enantioselectivities (91-97% ee) from readily available starting materials. The developed methodology was also successfully applied for the synthesis of novel β-amino ethers containing thiophenyl and pyridyl fragments. Mexiletine (Figure 1) is an effective sodium channel blocker used as an antiarrhythmic and analgesic oral drug. 1,2 Structure-activity studies in vivo 3 and in vitro 4 of pharmacologically active mexiletine indicate that its (−)-(R) enantiomer binds preferentially to the cardiac sodium channels. In addition, (−)-(R)-mexiletine is also more active than (+)-(S)-mexiletine on native skeletal muscular fibers. 1b,5 The use of mexiletine as a racemate in the treatment of neuromuscular disorders is limited due to its possible side effects. 6 The optically active mexiletine analogue (R)-2 (Figure 1) is 27-fold more potent than (R)-mexiletine in producing a tonic block and 23-fold more potent in condition of high frequency of stimulation (phasic block). 6 Recently, racemate 3 was established as a novel potent blocker of voltage-gated K + channels by using structure-based virtual screening in conjunction with electrophysiological assays in rat hippocampal neurons. 7 The preparation of mexiletine enantiomers has been reported previously by several groups. Generally, the methods involved resolution of racemic intermediates, 8 enzymatic hydrolysis of an N-acyl derivative, 9 or using a stereospecific, four-step procedure, in 7.2% overall yield. 8b Flippin and co-workers 10 reported a convenient procedure for the preparation of stereoisomers of mexiletine, but the scope of products was limited by the availability of chiral substrates and expensive chromium tricarbonyl complexes of aryl halides: hence, some amines were provided in the racemate form. Although Franchini's group 6 synthesized the stereoisomers of mexiletine analogues, the use of 2-phenyloxirane as chiral source restricted

Tetrahedron: Asymmetry, 2006

Novel spiroborate esters derived from nonracemic 1,2-amino alcohols were examined as chiral catal... more Novel spiroborate esters derived from nonracemic 1,2-amino alcohols were examined as chiral catalysts in the borane reduction of acetophenone and other aromatic ketones at room temperature. The optically active alcohols were obtained in excellent chemical yields and enantioselectivities up to 99% ee with 10% of catalyst.

Tetrahedron: Asymmetry, 2009

Tetrahedron, 1999

The α-alkylation and silylation of para substituted acetophenones, 1-and 2-indanone (O-TBS) oxime... more The α-alkylation and silylation of para substituted acetophenones, 1-and 2-indanone (O-TBS) oximes at various reaction conditions, were studied. Optimum conversions from 82% to 100% were afforded for the alkylation and silylation of these (O-TBS) ketoximes with LDA at −78 °C, using electrophiles, such as, methyl iodide, ethylbromide, benzyl bromide and trimethylchlorosilane.

Synthetic Communications, 1998

Grignard reagents add to benzonitrile at low temperature catalyzed by CuBr and TBSCl affording N-... more Grignard reagents add to benzonitrile at low temperature catalyzed by CuBr and TBSCl affording N-TBS ketimines, which were investigated as intermediaries for the synthesis of primary amines and ketones. N-silylimines were easily obtained by an organolithium addition to benzonitrile followed by a reaction with TBSCl in CH2Cl2. In situ reduction of these imines by BH3 and 1,3,2-oxazaborolidines 1 or 2

The Journal of Organic Chemistry, 2005

Rearrangements O 0140 Facile Rearrangement of O-Silylated Oximes on Reduction with Boron Trifluor... more Rearrangements O 0140 Facile Rearrangement of O-Silylated Oximes on Reduction with Boron Trifluoride/Borane.-Aromatic O-triisopropylsilyl ketoximes efficiently undergo rearrangement to cyclic and acyclic aniline derivatives which are isolated as hydrochlorides.-(ORTIZ-MARCIALES*, M.

Tetrahedron: Asymmetry, 2007

Tetrahedron: Asymmetry, 2016

A practical and convenient method for the efficient and regio- and stereoselective ring-opening o... more A practical and convenient method for the efficient and regio- and stereoselective ring-opening of enantiopure monosubstituted epoxides by sodium azide under hydrolytic conditions is reported. The ring-opening of enantiopure styryl and pyridyl (S)-epoxides by N3 (-) in hot water takes place preferentially at the internal position with complete inversion of configuration to produce (R)-2-azido ethanols with up to 99% enantio- and regioselectivity, while the (S)-adamantyl oxirane provides mainly the (S)-1-adamantyl-2-azido ethanol in excellent yield. In general, 1,2-amino ethanols were obtained in high yield and excellent enantiopurity by the reduction of the chiral 1,2-azido ethanols with PPh3 in water/THF, and then converted into the Boc or acetamide derivatives.

Tetrahedron Letters, 2012

Tetrahedron Letters, 2000

The reduction of aromatic oxime ethers by borane and organoboron reagents often affords good yiel... more The reduction of aromatic oxime ethers by borane and organoboron reagents often affords good yields of the hydroxyl amine or the amine, depending on the structure and reaction conditions.[8, 9 and 10] However, Liu et al. [11] observed high yields of unidentified side-...

The Journal of Organic Chemistry, 2011

An enantioselective borane-mediated reduction of a variety of 2-haloketones with 10% spiroaminobo... more An enantioselective borane-mediated reduction of a variety of 2-haloketones with 10% spiroaminoborate ester 1 as catalyst is described. By a simple basic workup of 2-halohydrins, optically active epoxides are obtained in high yield and with excellent enantiopurity (up to 99% ee). Ring-opening of oxiranes with phenoxides or sodium azide is investigated under different reaction conditions affording nonracemic 1,2-hydroxy ethers and 1,2-azido alcohols with excellent enantioselectivity (99% ee) and in good to high chemical yield.

Synthetic Communications, 2003

... DOI: 10.1081/SCC-120015717 Margarita Ortiz-Marciales a b * , Melvin De Jesús a , Dyliana Figu... more ... DOI: 10.1081/SCC-120015717 Margarita Ortiz-Marciales a b * , Melvin De Jesús a , Dyliana Figueroa a , Jesús Hernández a , Leslie Vázquez a , Rafael Vega a , Eduardo M. Morales a & José A. López a pages 311-323. Available ...

ChemInform, 1999

ketones ketones (benzene compounds) Q 0350

Acta crystallographica. Section C, Crystal structure communications, 2004

The reaction of (S)-alpha,alpha-diphenylprolinol with an excess of borane-tetrahydrofuran complex... more The reaction of (S)-alpha,alpha-diphenylprolinol with an excess of borane-tetrahydrofuran complex yields a stable crystalline material with the composition C34H38B2N2O2, which features a borane adduct of a spirocyclic structure with two oxazaborolidine rings joined by a central tetrahedral B atom. This dimeric oxazaborolidine complex, viz. 3,3,3',3'-tetraphenyl-1,1'-spirobi(3a,4,5,6-tetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole)-7-borane, is the dominant product under various reaction conditions; its crystal structure is consistent with 11B, 1H and 13C NMR and IR analyses.

Journal of Organic Chemistry, Oct 28, 2005

[reaction: see text] Aromatic O-triisopropylsilyl ketoximes were efficiently rearranged to cyclic... more [reaction: see text] Aromatic O-triisopropylsilyl ketoximes were efficiently rearranged to cyclic and acyclic aniline derivatives on reduction with BF3-ethearate/borane. The bulk of the substituents on the silicon atom, the size of the aliphatic ring, and the presence of alkoxy substituents on the aryl group all play an important role in the aniline.

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.

The Journal of Organic Chemistry, 2008

A practical and efficient procedure for the enantioselective synthesis of mexiletine analogues wi... more A practical and efficient procedure for the enantioselective synthesis of mexiletine analogues with use of 10% of spiroborate ester 6 as chirality transfer agent is presented. A variety of mexiletine analogues were prepared in good yield with excellent enantioselectivities (91-97% ee) from readily available starting materials. The developed methodology was also successfully applied for the synthesis of novel β-amino ethers containing thiophenyl and pyridyl fragments. Mexiletine (Figure 1) is an effective sodium channel blocker used as an antiarrhythmic and analgesic oral drug. 1,2 Structure-activity studies in vivo 3 and in vitro 4 of pharmacologically active mexiletine indicate that its (−)-(R) enantiomer binds preferentially to the cardiac sodium channels. In addition, (−)-(R)-mexiletine is also more active than (+)-(S)-mexiletine on native skeletal muscular fibers. 1b,5 The use of mexiletine as a racemate in the treatment of neuromuscular disorders is limited due to its possible side effects. 6 The optically active mexiletine analogue (R)-2 (Figure 1) is 27-fold more potent than (R)-mexiletine in producing a tonic block and 23-fold more potent in condition of high frequency of stimulation (phasic block). 6 Recently, racemate 3 was established as a novel potent blocker of voltage-gated K + channels by using structure-based virtual screening in conjunction with electrophysiological assays in rat hippocampal neurons. 7 The preparation of mexiletine enantiomers has been reported previously by several groups. Generally, the methods involved resolution of racemic intermediates, 8 enzymatic hydrolysis of an N-acyl derivative, 9 or using a stereospecific, four-step procedure, in 7.2% overall yield. 8b Flippin and co-workers 10 reported a convenient procedure for the preparation of stereoisomers of mexiletine, but the scope of products was limited by the availability of chiral substrates and expensive chromium tricarbonyl complexes of aryl halides: hence, some amines were provided in the racemate form. Although Franchini's group 6 synthesized the stereoisomers of mexiletine analogues, the use of 2-phenyloxirane as chiral source restricted

Tetrahedron: Asymmetry, 2006

Novel spiroborate esters derived from nonracemic 1,2-amino alcohols were examined as chiral catal... more Novel spiroborate esters derived from nonracemic 1,2-amino alcohols were examined as chiral catalysts in the borane reduction of acetophenone and other aromatic ketones at room temperature. The optically active alcohols were obtained in excellent chemical yields and enantioselectivities up to 99% ee with 10% of catalyst.

Tetrahedron: Asymmetry, 2009

Tetrahedron, 1999

The α-alkylation and silylation of para substituted acetophenones, 1-and 2-indanone (O-TBS) oxime... more The α-alkylation and silylation of para substituted acetophenones, 1-and 2-indanone (O-TBS) oximes at various reaction conditions, were studied. Optimum conversions from 82% to 100% were afforded for the alkylation and silylation of these (O-TBS) ketoximes with LDA at −78 °C, using electrophiles, such as, methyl iodide, ethylbromide, benzyl bromide and trimethylchlorosilane.

Synthetic Communications, 1998

Grignard reagents add to benzonitrile at low temperature catalyzed by CuBr and TBSCl affording N-... more Grignard reagents add to benzonitrile at low temperature catalyzed by CuBr and TBSCl affording N-TBS ketimines, which were investigated as intermediaries for the synthesis of primary amines and ketones. N-silylimines were easily obtained by an organolithium addition to benzonitrile followed by a reaction with TBSCl in CH2Cl2. In situ reduction of these imines by BH3 and 1,3,2-oxazaborolidines 1 or 2

The Journal of Organic Chemistry, 2005

Rearrangements O 0140 Facile Rearrangement of O-Silylated Oximes on Reduction with Boron Trifluor... more Rearrangements O 0140 Facile Rearrangement of O-Silylated Oximes on Reduction with Boron Trifluoride/Borane.-Aromatic O-triisopropylsilyl ketoximes efficiently undergo rearrangement to cyclic and acyclic aniline derivatives which are isolated as hydrochlorides.-(ORTIZ-MARCIALES*, M.

Tetrahedron: Asymmetry, 2007

Tetrahedron: Asymmetry, 2016

A practical and convenient method for the efficient and regio- and stereoselective ring-opening o... more A practical and convenient method for the efficient and regio- and stereoselective ring-opening of enantiopure monosubstituted epoxides by sodium azide under hydrolytic conditions is reported. The ring-opening of enantiopure styryl and pyridyl (S)-epoxides by N3 (-) in hot water takes place preferentially at the internal position with complete inversion of configuration to produce (R)-2-azido ethanols with up to 99% enantio- and regioselectivity, while the (S)-adamantyl oxirane provides mainly the (S)-1-adamantyl-2-azido ethanol in excellent yield. In general, 1,2-amino ethanols were obtained in high yield and excellent enantiopurity by the reduction of the chiral 1,2-azido ethanols with PPh3 in water/THF, and then converted into the Boc or acetamide derivatives.

Tetrahedron Letters, 2012

Tetrahedron Letters, 2000

The reduction of aromatic oxime ethers by borane and organoboron reagents often affords good yiel... more The reduction of aromatic oxime ethers by borane and organoboron reagents often affords good yields of the hydroxyl amine or the amine, depending on the structure and reaction conditions.[8, 9 and 10] However, Liu et al. [11] observed high yields of unidentified side-...

The Journal of Organic Chemistry, 2011

An enantioselective borane-mediated reduction of a variety of 2-haloketones with 10% spiroaminobo... more An enantioselective borane-mediated reduction of a variety of 2-haloketones with 10% spiroaminoborate ester 1 as catalyst is described. By a simple basic workup of 2-halohydrins, optically active epoxides are obtained in high yield and with excellent enantiopurity (up to 99% ee). Ring-opening of oxiranes with phenoxides or sodium azide is investigated under different reaction conditions affording nonracemic 1,2-hydroxy ethers and 1,2-azido alcohols with excellent enantioselectivity (99% ee) and in good to high chemical yield.

Synthetic Communications, 2003

... DOI: 10.1081/SCC-120015717 Margarita Ortiz-Marciales a b * , Melvin De Jesús a , Dyliana Figu... more ... DOI: 10.1081/SCC-120015717 Margarita Ortiz-Marciales a b * , Melvin De Jesús a , Dyliana Figueroa a , Jesús Hernández a , Leslie Vázquez a , Rafael Vega a , Eduardo M. Morales a & José A. López a pages 311-323. Available ...

ChemInform, 1999

ketones ketones (benzene compounds) Q 0350

Acta crystallographica. Section C, Crystal structure communications, 2004

The reaction of (S)-alpha,alpha-diphenylprolinol with an excess of borane-tetrahydrofuran complex... more The reaction of (S)-alpha,alpha-diphenylprolinol with an excess of borane-tetrahydrofuran complex yields a stable crystalline material with the composition C34H38B2N2O2, which features a borane adduct of a spirocyclic structure with two oxazaborolidine rings joined by a central tetrahedral B atom. This dimeric oxazaborolidine complex, viz. 3,3,3',3'-tetraphenyl-1,1'-spirobi(3a,4,5,6-tetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole)-7-borane, is the dominant product under various reaction conditions; its crystal structure is consistent with 11B, 1H and 13C NMR and IR analyses.