104 research outputs found
Solvent-free synthesis of quaternary α-hydroxy α-trifluoromethyl diazenes: the key step of a nucleophilic formylation strategy
An efficient, scalable and operationally simple one-pot, 2-step strategy for the nucleophilic formylation of
trifluoromethyl ketones is presented. The key step is an unprecedented diaza-carbonyl-ene reaction of
formaldehyde tert-butyl hydrazone and trifluoromethyl ketones under solvent-free conditions. This reaction
proved to be very fast, clean and high-yielding, affording densely functionalised α-hydroxy
α-trifluoromethyl diazenes. The ensuing diazene-to-aldehyde transformation, avoiding protection/deprotection
reactions and chromatographic purifications, and subsequent derivatizations in a one-pot
fashion provide a direct entry to a variety of useful trifluoromethylated building blocks.We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).This work was supported by the Ministerio de EconomĂa y
Competitividad of Spain (CTQ2013-48164-C2-1-P, CTQ2013-48164-C2-2-P, and predoctoral fellowship to E. M.), European FEDER funds and the Junta de AndalucĂa (Grant 2012/FQM 1078). D. M. acknowledges Universidad de Sevilla for a postdoctoral
contract.Peer reviewe
Hydrazones as Singular Reagents in Asymmetric Organocatalysis
This Minireview summarizes strategies and developments regarding the use of hydrazones as reagents in asymmetric organocatalysis, their distinct roles in nucleophile–electrophile, cycloaddition, and cyclization reactions. The key structural elements governing the reactivity of these reagents in a preferred pathway will be discussed, as well as their different interactions with organocatalysts, leading to diverse activation modes. Along these studies, the synthetic equivalence of N-monoalkyl, N,N-dialkyl, and N-acyl hydrazones with several synthons is also highlighted. Emphasis is also put on the mechanistic studies performed to understand the observed reactivities. Finally, the functional group transformations performed from the available products has also been analyzed, highlighting the synthetic value of these methodologies, which served to access numerous families of valuable multifunctional compounds and nitrogen-containing heterocycles.Ministerio de EconomĂa y Competitividad CTQ2013-48164-C2-1-P, CTQ201348164-C2-2-PEuropean FEDER fundsJunta de AndalucĂa 2012/FQM 107
Dynamic Kinetic Resolution of Hetero biaryl Ketones by Zinc- Catalyzed Asymmetr ic Hydrosil ylation
Adiastereo-
and
highly
enantioselective
dynamic
kinetic
resolution
(DKR)
of configurationally
labile
hetero-
biaryl
ketones
is described.
The
DKR
proceeds
by zinc-
catalyze
dhydrosilylation
of the carbonyl
group
,thus leading
to
secondary
alcohols
bearing
axial
and
central
chirality
.The
strategy
relies
on the labilization
of the stereogenic
axis
that
takes
place
thanks
to aLewis
acid–base
interaction
between
anitrogen
atom
in the heterocycle
and
the ketone
carbonyl
group
.The synthetic
utility
of the methodology
is demonstrated
through
stereospecific
transformations
into either
N,N-ligands
or appealing
axially
chiral,
bifunctional
thiourea
organocata-
lysts.Ministerio de Ciencia e InnovaciĂłn (Grants CTQ2016-76908-C2-1-P, CTQ2016-76908-C2-2-P, contract RYC-2013-12585)European FEDER FundsJunta de AndalucĂa (Grant 2012/FQM 10787)European Union - Marie SkĹ‚odowska-Curie (COFUND—Grant Agreement n 8 8 291780
Synthesis of IAN-type N,N-Ligands via Dynamic Kinetic Asymmetric Buchwald-Hartwig Amination
The Pd-catalyzed coupling of racemic heterobiaryl bromides, triflates, or nonaflates with aryl/alkyl primary amines using QUINAP as the ligand provides the corresponding axially chiral heterobiaryl amines with excellent yields and enantioselectivities. Reactivity and structural studies of neutral and cationic oxidative addition intermediates support a dynamic kinetic asymmetric amination mechanism based on the labilization of the stereogenic axis in the latter and suggest that coordination of the amine to the Pd center is the stereodetermining step.Ministerio de Ciencia e InnovaciĂłn CTQ2013-48164-C2-1-P, CTQ2013-48164-C2-2-P, RYC-2013-12585 for A.R.European FEDER FundsJunta de AndalucĂa 2012/FQM 1078
A Dynamic Kinetic Asymmetric Heck Reaction for the Simultaneous Generation of Central and Axial Chirality
A highly diastereo- and enantioselective, scalable Pd-catalyzed dynamic kinetic asymmetric Heck reaction of heterobiaryl sulfonates with electron-rich olefins is described. The coupling of 2,3-dihydrofuran or N-boc protected 2,3-dihydropyrrole with a variety of quinoline, quinazoline, phthalazine, and picoline derivatives takes place with simultaneous installation of central and axial chirality, reaching excellent diastereo- and enantiomeric excesses when in situ formed [Pd0/DM-BINAP] was used as the catalyst, with loadings reduced down to 2 mol % in large scale reactions. The coupling of acyclic, electron-rich alkenes can also be performed using a [Pd0/Josiphos ligand] to obtain axially chiral heterobiaryl α-substituted alkenes in high yields and enantioselectivities. Products from Boc-protected 2,3-dihydropyrrole can be easily transformed into N,N ligands or appealing axially chiral, bifunctional proline-type organocatalysts. Computational studies suggest that a β-hydride elimination is the stereocontrolling step, in agreement with the observed stereochemical outcome of the reaction.Ministerio de Ciencia e InnovaciĂłn (Grants CTQ2016-76908-C2-1-P; CTQ2016-76908-C2-2-P; CTQ2016-78083-P; RYC-2013-12585)European Commission (FEDER Programme)Junta de AndalucĂa (Grant 2012/FQM 10787)Universidad de Sevilla (Grant No. 1800511201)European Union - Marie SkĹ‚odowska-Curie (COFUND—Grant Agreement nÂş 291780
Hydrazones as Singular Reagents in Asymmetric Organocatalysis
This Minireview summarizes strategies and developments regarding the use of hydrazones as reagents in asymmetric organocatalysis, their distinct roles in nucleophile–electrophile, cycloaddition, and cyclization reactions. The key structural elements governing the reactivity of these reagents in a preferred pathway will be discussed, as well as their different interactions with organocatalysts, leading to diverse activation modes. Along these studies, the synthetic equivalence of N-monoalkyl, N,N-dialkyl, and N-acyl hydrazones with several synthons is also highlighted. Emphasis is also put on the mechanistic studies performed to understand the observed reactivities. Finally, the functional group transformations performed from the available products has also been analyzed, highlighting the synthetic value of these methodologies, which served to access numerous families of valuable multifunctional compounds and nitrogen-containing heterocycles.Peer Reviewe
Synthesis of IAN-type N,N-Ligands via Dynamic Kinetic Asymmetric Buchwald-Hartwig Amination
The Pd-catalyzed coupling of racemic heterobiaryl bromides, triflates, or nonaflates with aryl/alkyl primary amines using QUINAP as the ligand provides the corresponding axially chiral heterobiaryl amines with excellent yields and enantioselectivities. Reactivity and structural studies of neutral and cationic oxidative addition intermediates support a dynamic kinetic asymmetric amination mechanism based on the labilization of the stereogenic axis in the latter and suggest that coordination of the amine to the Pd center is the stereodetermining step.Peer Reviewe
Red-Emitting Tetracoordinate Organoboron Chelates: Synthesis, Photophysical Properties, and Fluorescence Microscopy
Seven tetracoordinate organoboron fluorophores with heterobiaryl N,O- or N,N-chelate ligands were prepared and photophysically characterized (in toluene). The electronic variation of the heteroaromatic moiety provided a means for the fine-tuning of the UV/vis absorption and emission spectra. In the most interesting cases, the spectra were red-shifted to maximum absorbance at wavelengths longer than 500 nm and emission maxima between 620 and 660 nm. The pronounced intramolecular charge-transfer character of the dyes yielded large Stokes shifts (3500-5100 cm), while maintaining appreciable fluorescence quantum yields of up to 0.2 for emission maxima longer than 600 nm. The lipophilic character of the dyes enabled their application as stains of vesicle substructures in confocal fluorescence microscopy imaging.Ministerio de EconomĂa y Competitividad CTQ2014-54729 - C2 - 1 - P for U.P., CTQ2013 - 48164 - C2 - 1 - P , CTQ2013 - 48164 - C2 - 2 - P for A.R., CTQ2013 - 41339 - P, CTQ2015 - 71896 - REDT for E.P.I., RamĂłn y Cajal contract RYC - 2013 - 12585 for A.R.FEDER FundJunta de AndalucĂa 2012/FQM - 2140 for U.P., 2009/FQM - 4537 and 2012/FQM - 1078 for A.R
Formaldehyde tert-butyl hydrazone as a formyl anion equivalent: asymmetric addition to carbonyl compounds
The asymmetric 1,2-addition of formyl anion equivalents to carbonyl compounds is a powerful synthetic
tool that ideally provide access to highly functionalizable a-hydroxy aldehydes in an enantioselective fashion.
In this context, the nucleophilic character of formaldehyde hydrazones, together with their remarkable
stability as monomeric species, has been exploited for the functionalization of diverse carbonyl compounds,
using initially auxiliary-based methodologies and, more recently, catalytic enantioselective versions. This
feature article highlights our research progress employing formaldehyde tert-butyl hydrazone as a versatile
formyl anion equivalent, in combination with bifunctional H-bonding organocatalysis. The design and
optimization of different catalytic systems, focusing on a dual activation of both reagents, is reviewed, as
well as the racemization free unmasking of the formyl group and representative product transformations for
the construction of valuable, densely functionalyzed chiral building blocks.Ministerio de EconomĂa y Competitividad de España (MINECO).CTQ2016-76908-C2-1-P y CTQ2016-76908-C2-2-PFondos FEDER de la UniĂłn Europea y Junta de AndalucĂa. P18-FR-3531 y US126286
Stroke: roles of B vitamins, homocysteine and antioxidants
19 páginas, 1 figura, 2 tablas.In the present review concerning stroke, we evaluate the roles of B vitamins, homocysteine and antioxidant vitamins. Stroke is a leading cause of death in developed countries. However, current therapeutic strategies for stroke have been largely unsuccessful. Several studies have reported important benefits on reducing the risk of stroke and improving the post-stroke-associated functional declines in patients who ate foods rich in micronutrients, including B vitamins and antioxidant vitamins E and C. Folic acid, vitamin B6 and vitamin B12 are all cofactors in homocysteine metabolism. Growing interest has been paid to hyperhomocysteinaemia as a risk factor for CVD. Hyperhomocysteinaemia has been linked to inadequate intake of vitamins, particularly to B-group vitamins and therefore may be amenable to nutritional intervention. Hence, poor dietary intake of folate, vitamin B6 and vitamin B12 are associated with increased risk of stroke. Elevated consumption of fruits and vegetables appears to protect against stroke. Antioxidant nutrients have important roles in cell function and have been implicated in processes associated with ageing, including vascular, inflammatory and neurological damage. Plasma vitamin E and C concentrations may serve as a biological marker of lifestyle or other factors associated with reduced stroke risk and may be useful in identifying those at high risk of stroke. After reviewing the observational and intervention studies, there is an incomplete understanding of mechanisms and some conflicting findings; therefore the available evidence is insufficient to recommend the routine use of B vitamins, vitamin E and vitamin C for the prevention of stroke. A better understanding of mechanisms, along with well-designed controlled clinical trials will allow further progress in this area.Peer reviewe
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