Stereoselective Aza-Henry Reaction of Chiral tert-Butanesulfinyl Imines with Methyl or Ethyl 4-Nitrobutanoate: Easy Access to Enantioenriched 6-Substituted Piperidine-2,5-diones

The base-catalyzed addition of 4-nitrobutanoates 6 to N-tert-butanesulfinyl imines 8 under solvent-free reaction conditions proceeded with high face diastereoselectivity. The resulting β-nitroamine derivatives 9 were easily transformed into 6-substituted piperidine-2,5-diones 11 upon removal of the sulfinyl group with concomitant δ-lactam formation and functional group transformation under Nef reaction conditions.This work was generously supported by the Spanish Ministerio de Ciencia e Innovación (Grant Nos. CTQ2011-24165, and Consolider Ingenio 2010-CSD-2007-00006), the Generalitat Valenciana (Grant No. PROMETEO/2009/039 and FEDER) and the University of Alicante. M.J.G.M. thanks the University of Alicante for a predoctoral fellowship

Stereoselective Synthesis of 2-(2-Aminoalkyl)- and 1,3-Disubstituted Tetrahydro-1H-pyrido[4,3-b]- Benzofuran and Indole Derivatives

The addition of an allenyl indium intermediate to chiral N-tert-butanesulfinyl imines 7 proceeds with high levels of diastereocontrol. The resulting homopropargylic amine derivatives 10 were transformed into 2-(2-aminoalkyl)benzofuran and indole derivatives 13 and 19, after Sonogashira coupling with o-iodophenol or o-iodoaniline, followed by formation of the heteroaromatic ring through an intramolecular cyclization. Enantioenriched tetrahydropyrido-benzofuran and indole derivatives 16 and 21 were prepared through a Pictet-Spengler condensation of the free amines derived from compounds 15 and 20, involving the nucleophilic 3-position of the benzofuran or indole moiety.We thank the continued financial support from our Ministerio de Ciencia e Innovación (MCINN; projects CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO; projects CTQ2014-53695-P, CTQ2014-51912-REDC), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017) and the University of Alicante

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

We thank the Spanish Ministerio de Ciencia e Innovación (Grant Nos. CTQ2007-65218 and Consolider Ingenio 2010-CSD-2007-00006 and CTQ2011-24165), the Generalitat Valenciana (Grant No. PROMETEO/2009/039 and FEDER), and the University of Alicante for generous and continuous financial support

Selective palladium(II)-mediated oxidation of homoallylic N-tert-butanesulfinyl amine derivatives

The palladium(II)-catalyzed oxidation of homoallylic amine derivatives resulting from the allylation of N-tert-butanesulfinyl imines with allyl bromide led to the formation of the corresponding terminal allylic acetates in a regioselective fashion in moderate yields. In the case of the homoallylic amine derivatives obtained using cyclohexenyl bromide as the allylating reagent, the allylic oxidation took place with high regio- and diastereoselectivity and yields ranging from 40 to 85%.We thank the continued financial support from Ministerio de Economía y Competitividad (MINECO; projects CTQ2014-53695-P and CTQ2014-51912-REDC), the Generalitat Valenciana (PROMETEO 2009/039 and PROMETEOII/2014/017) and the University of Alicante

Diastereoselective allylation and crotylation of N-tert-butanesulfinyl imines with allylic alcohols

The palladium-catalyzed allylation of N-tert-butanesulfinyl imines with allylic alcohols in the presence of InI as reducing reagent takes place with high diastereoselectivity in reasonable yields. The reaction with crotyl alcohol is totally regioselective, leading to the anti-diastereomer as the main reaction product.Spanish Ministerio de Ciencia e Innovación (Grant No. CTQ2011-24165), the Generalitat Valenciana (Grant No. PROMETEO/2009/039 and FEDER) and the University of Alicante. OSRB thanks CNPq of Brazil for a fellowship

Synthesis of Chiral 1,3-Dienes through Ring-Closing Metathesis of Enantioenriched Enynes: Potential Precursors of Morphane Analogs

A simple methodology for the synthesis of enynes by indium mediated diastereoselective allylation of aromatic N-tert-butanesulfinylimines bearing alkenyl groups at ortho-position with allyl bromide has been developed. The addition of the allyl indium intermediate to the chiral imine took place with excellent diastereoselectivity. Ruthenium-catalyzed ring-closing metathesis of the resulting enynes provided the expected cyclic 1,3-dienes in good to moderate yields. These chiral dienes are potential precursors of biologically and pharmacologically active morphane derivatives.We thank the continued financial support from our Ministerio de Ciencia e Innovación (MCINN; CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO; projects CTQ2014-53695-P, CTQ2014-51912-REDC, CTQ2016-81797-REDC, CTQ2017-85093-P), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017), and the University of Alicante

Evaluación continua y análisis de resultados en las asignaturas del grado de química impartidas por el departamento de química orgánica

En esta comunicación se pondrán en común las experiencias de distintos docentes del Departamento que han impartido asignaturas de Química Orgánica tanto en la antigua Licenciatura como en el nuevo Grado de Químicas. Las asignaturas en que se focaliza el estudio, debido a que son de obligada realización, son: Química Orgánica, Estereoquímica Orgánica, Determinación Estructural de Compuestos Orgánicos y Química Orgánica Avanzada. El objetivo de este estudio permitirá evaluar los cambios que se han llevado a cabo desde el punto de vista de las nuevas metodologías docentes que se han debido aplicar así como de los cambios de contenido que han sufrido las asignaturas. También se pretende evaluar los resultados obtenidos por los alumnos resaltando y comparando las ventajas e inconvenientes encontradas en el nuevo plan de estudios. Además, como fin último este estudio pretende poner en común aquellas estrategias que mejor resultado hayan dado desde distintos ámbitos docentes para aplicarlas en futuros cursos

Compuestos organolíticos nitrogenofuncionalizados. Aplicaciones en síntesis orgánica

Se describe la preparacion de compuestos organolíticos b-funcionalizados con hibridación por metalación de los correspondientes cloroderivados con litio-naftaleno a -78 grados c. Se estudia la estabilidad de estos sistemas y su reactividad frente a distintos electrófilos (agua, óxido de deuterio, oxígeno, dióxido de carbono, disulfuro de dimetilo, y compuestos carbonílicos). También se prepara un compuesto organolítico -funcionalizado a través de un proceso similar. Este sistema es estable a temperatura ambiente y de igual modo se estudia su reactividad frente a distintos agentes electrófilos. Finalmente, gran cantidad de alil y 2-metilalilaminas han sido regio- y estereoselectivamente litiadas con t-butillitio para dar los correspondientes compuestos organolíticos -aminofuncionalizados con hibridación y estereoquímica z. Estos sistemas por reacción con electrófilos conducen a moléculas orgánicas polifuncionalizadas. En el caso de la 2-metilalilianilina la litiación alílica tiene lugar exclusivamente. De especial interés es la reacción con carbonato de dietilo para dar butirolactamas, las cuales son importantes intermediarios en la síntesis de diferentes productos naturales

Arene-promoted lithiation of 1,n-dihaloalkanes (n = 2-6): a comparative study

The reaction of 1,n-dichloroalkanes 3a (n = 2-6) with an excess of lithium powder and a catalytic amount of 4,4’-di-tert-butylbiphenyl (DTBB; 2.5 mol %) in the presence of different carbonyl compounds [ButCHO, PhCHO, Et2CO, (CH2)4CO, (CH2)5CO, (CH2)7CO, (-)-menthone], in THF at -78 ºC leads, after hydrolysis with water, to the expected 1,(n+2)-diols 4, yields being < 25% for n = 2, 3 and in the range of 45-79% for n = 4-6. When the same protocol is applied to 1,n-bromochloroalkanes 3b and 1,n-dibromoalkanes 3c (n = 2-6), diols 4 are obtained in general with lower yields.This work was supported by the Spanish Ministerio de Educación y Ciencia (MEC; grant no. CTQ2004-01261) and the Generalitat Valenciana (GV; grants no. GRUPOS05/052 and GRUPOS05/058)

Stereoselective synthesis of indoline, tetrahydroquinoline, and tetrahydrobenzazepine derivatives from o-bromophenyl N-tert-butylsulfinyl aldimines

The diastereoselective addition of an allylic indium intermediate to chiral o-bromophenyl sulfinyl imine 4 proceeded with good levels of diastereoselectivity. The resulting homoallylic amine derivatives were transformed into lactams 7 and 12, which upon copper-mediated intramolecular N-arylation led to the formation of benzo-fused 1-azabicyclo[j.k.0]alkanes 8 and 13. Benzo-fused 2-allyl-substituted heterocycles 14 could also be prepared by means of a palladium-catalyzed N-arylation of the corresponding free amines. The synthesis of the alkaloid (−)-angustureine was easily accomplished from (S)-2-allyltetrahydroquinoline (14b).Spanish Ministerio de Ciencia e Innovación (Grants CTQ2007-65218, Consolider Ingenio 2010-CSD-2007-00006, and CTQ2011-24165), the Generalitat Valenciana (Grant PROMETEO/2009/039 and FEDER), and the University of Alicante