Discovering new arene-catalyzed lithiations

La litiació catalitzada per hidrocarburs aromàtics és una metodologia útil i versàtil que promou els processos de litiació en condicions de reacció molt suaus. Aquest informe presenta els resultats recents en l'aplicació d'aquesta tecnologia, principalment en els camps següents: a) carbolitiació intramolecular vs. obertura d'anells en litiometilcicloalcans, b) la generació de sintons de diliti com a precursors dels èters bicíclics i espiroèters, les principals unitats de productes naturals biològicament actius, c) desprotecció general dels diversos compostos protegits que contenen oxigen, sofre i nitrogen en condicions no hidrolítiques, i d) la preparació de nanopartícules de níquel i la seva aplicació en reaccions de formació d'enllaços carboni-carboni i carboni-nitrogen.Arene-catalyzed lithiation is a useful and versatile methodology that promotes lithiation processes under very mild reaction conditions. This report presents recent results in the application of this technology, mainly in the following fields: (a) intramolecular carbolithiation vs. ring-opening in lithiomethylcycloalkanes; (b) the generation of dilithium synthons as precursors of bicyclic and spiro ethers, major units in biological active natural products; (c) general deprotection of different oxygen-, sulfur-, and nitrogen-containing protected compounds under non-hydrolytic conditions; and (d) the preparation of nickel nanoparticles and their application in carbon-carbon and carbon-nitrogen bond formation reactions

Chiral benzimidazoles as hydrogen bonding organocatalysts

Several bifunctional organocatalysts bearing the benzimidazole unit have been designed in order to act as bifunctional systems by hydrogen bonding. Chiral 2-aminobenzimidazoles are conformational rigid guanidines able to catalyze enantioselectively Michael reaction, direct SN1 of alcohols, and aldol reactions. Some of these organocatalysts can be easily recovered by simple isolation methods and reused without loss of catalytic activity. Related (2-aminoalkyl)benzimidazoles have been used as chiral organocatalysts in aldol and amination reactions of carbonyl compounds.The Spanish Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2010-20387, and Consolider Ingenio 2010, CSD2007-00006), the Spanish Ministerio de Economia y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), FEDER – Spain, the Generalitat Valenciana – Spain (PROMETEO 2009/039 and PROMETEOII/2014/017), and the University of Alicante are gratefully acknowledged for financial support

Recent advances in the use of chiral aldimines in asymmetric synthesis

Chiral N-(tert-butyl)sulfinyl aldimines easily prepared from commercially available compounds have been used as starting materials for the following processes: (i) hydrogen transfer, (ii) addition of zincates, (iii) In-promoted allylation, and (iv) addition of zinc enolates. In all cases, the final desulfinylation to yield the expected chiral α-substituted primary amines was easily performed with hydrochloric acid in an organic solvent. This methodology has been successfully applied to the preparation of chiral natural products such as alkaloids and amino acids.We thank the continuous financial support from the Ministry of Science and Innovation (Ministerio de Ciencia e Innovación (MICINN), Projects CTQ2007-62771/BQU, CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24151, and CTQ20122-24165), the Ministry of Economy and Competitiveness (Ministerio de Economía y Competitividad (MINECO), Projects CTQ2013-43446-P, CTQ2014-51912-REDC, and CTQ2014-53695-P), the Fondo Europeo de Desarrollo Regional (FEDER), the Government of the region of Valencia (Generalitat Valenciana, Project PROME-TEOII/2014/017), and the University of Alicante

Synthesis of alkaloids by a diastereoselective allylation of chiral N-sulfinyl imines

The indium-promoted allylation of chiral N-sulfinyl imines represents a useful and versatile procedure to prepare chiral protected homoallyl amines in a diastereoselective manner. Desulfinylation under acidic conditions liberates easily the corresponding enantioenriched homoallyl amines. This type of compounds can be easily manipulated synthetically in order to prepare a series of natural alkaloids in an enantiopure form, using simple transformations.We thank the continued financial support from our Ministerio de Ciencia e Innovación (MCINN; projects CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24151, CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO; projects CTQ2013-43446-P, CTQ2014-51912-REDC, CTQ2014-53695-P), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017) and the University of Alicante

Catalytic Asymmetric Transfer Hydrogenation of Imines: Recent Advances

In this review article recent developments in the asymmetric transfer hydrogenation of imines from 2008 up to today are presented. The main methodology involves either metal-catalyzed procedures in the presence of a chiral ligand or organocatalyzed technologies using a Hantzsch ester and a chiral BINOL-derived phosphoric acid. The most important procedures are collected, paying special attention to the application of this methodology in synthetic organic chemistry.We thank the continued financial support from our Ministerio de Ciencia e Innovación (MICINN; projects CTQ2007-62771/BQU, CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24151, CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO; projects CTQ2013-43446-P, CTQ2014-51912-REDC, CTQ2014-53695-P), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017), and the University of Alicante

Catalytic asymmetric transfer hydrogenation of ketones: recent advances

In this review, we consider the main processes for the asymmetric transfer hydrogenation of ketones from 2008 up today. The most effective organometallic compounds (derived from Ru, Rh, Ir, Fe, Os, Ni, Co, and Re) and chiral ligands (derived from amino alcohols, diamines, sulfur- and phosphorus-containing compounds, as well as heterocyclic systems) will be shown paying special attention to functionalized substrates, tandem reactions, processes under non-conventional conditions, supported catalysts, dynamic kinetic resolutions, the use of water as a green solvent, theoretical and experimental studies on reaction mechanisms, enzymatic processes, and finally applications to the total synthesis of biologically active organic molecules.We thank the continuous financial support from our Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2007-62771/BQU, CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24151, CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P, CTQ2014-51912-REDC, CTQ2014-53695-P), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017), and the University of Alicante

Indium Mediated Allylation of N-tert-Butanesulfinyl Imines with 1,3-Dibromopropene: Stereoselective Synthesis of Aziridines

The reaction of N-tert-butanesulfinyl imines 1 with 1,3-dibromopropene (2), in the presence of indium metal, in saturated aqueous solution of sodium bromide, produced bromohomoallylamine derivatives 3 with total facial diastereoselectivity for the imine addition, and moderate yields. These compounds were easily transformed into the corresponding vinyl aziridines 5 upon deprotonation with KHMDS in THF, the intramolecular cyclization taking place in a stereospecific manner in moderate to high yields.We thank the continued financial support from our Ministerio de Economía y Competitividad (MINECO; project CTQ2014-53695-P, CTQ2014-51912-REDC, CTQ2016-81797-REDC, CTQ2017-85093-P), FEDER, the Generalitat Valenciana (PROMETEOII/2014/017), and the University of Alicante

Enantiodivergent Approach to the Synthesis of Cis-2,6-Disubstituted Piperidin-4-ones

Enantiopure β-amino ketone derivatives were synthesized by decarboxylative Mannich reaction of chiral N-tert-butanesulfinyl imines with β-keto acids and were subsequently transformed into cis-2,6-disubstituted piperidin-4-ones through an organocatalyzed condensation with aldehydes. Both enantiomers were accessible from the same precursors by inverting the order in the reaction sequence of the aldehydes involved in the imine formation and the intramolecular Mannich condensation. The synthesis of the piperidine alkaloids (+)-241D, (−)-epimyrtine, and (−)-lasubine II demonstrated the utility of this methodology.We acknowledge the continued financial support from the Spanish Ministerio de Economía y Competitividad (MINECO; projects CTQ2014-53695-P, CTQ2014-51912-REDC, CTQ2016-81797-REDC, CTQ2017-85093-P), FEDER, the Generalitat Valenciana (PROMETEOII/2014/017), and the University of Alicante

1,3-Dipolar cycloadditions of azomethine imines

Azomethine imines are considered 1,3-dipoles of the aza-allyl type which are transient intermediates and should be generated in situ but can also be stable and isolable compounds. They react with electron-rich and electron-poor olefins as well as with acetylenic compounds and allenoates mainly by a [3 + 2] cycloaddition but they can also take part in [3 + 3], [4 + 3], [3 + 2 + 2] and [5 + 3] with different dipolarophiles. These 1,3-dipolar cycloadditions (1,3-DC) can be performed not only under thermal or microwave conditions but also using metallo- and organocatalytic systems. In recent years enantiocatalyzed 1,3-dipolar cycloadditions have been extensively considered and applied to the synthesis of a great variety of dinitrogenated heterocycles with biological activity. Acyclic azomethine imines derived from mono and disubstituted hydrazones could be generated by prototropy under heating or by using Lewis or Brønsted acids to give, after [3 + 2] cycloadditions, pyrazolidines and pyrazolines. Cyclic azomethine imines, incorporating a C–N bond in a ring, such as isoquinolinium imides are the most widely used dipoles in normal and inverse-electron demand 1,3-DC allowing the synthesis of tetrahydro-, dihydro- and unsaturated pyrazolo[1,5-a]isoquinolines in racemic and enantioenriched forms with interesting biological activity. Pyridinium and quinolinium imides give the corresponding pyrazolopyridines and indazolo[3,2-a]isoquinolines, respectively. In the case of cyclic azomethine imines with an N–N bond incorporated into a ring, N-alkylidene-3-oxo-pyrazolidinium ylides are the most popular stable and isolated dipoles able to form dinitrogen-fused saturated and unsaturated pyrazolopyrazolones as racemic or enantiomerically enriched compounds present in many pharmaceuticals, agrochemicals and other useful chemicals.We acknowledge continued financial support from the Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2007-62771/BQU, CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24151, and CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P, CTQ2014-51912-REDC, and CTQ2014-53695-P), FEDER, the Generalitat Valenciana (PROMETEO 2009/039 and PROMETEOII/2014/017), and the University of Alicante