Teodor Parella

Direct observation of CuI/CuIII redox steps relevant to Ullmann-type coupling reactions

A series of aryl–copper(III)-halide complexes have been synthesized and characterized by NMR and UV-visible spectroscopy, cyclic voltammetry and X-ray crystallography. These complexes closely resemble elusive intermediates often invoked in catalytic reactions, such as Ullmann–Goldberg cross-coupling reactions, and their preparation has enabled direct observation and preliminary characterization of aryl halide reductive elimination from CuIII and oxidative addition to CuI centers. In situ spectroscopic studies (1H NMR, UV-visible) of a Cu-catalyzed C–N coupling reaction provides definitive evidence for the involvement of an aryl-copper(III)-halide intermediate in the catalytic mechanism. These results provide the first direct observation of the CuI/CuIII redox steps relevant to Ullmann-type coupling reactions.

Facile C−H Bond Cleavage via a Proton-Coupled Electron Transfer Involving a C−H···CuII Interaction

The present study provides mechanistic details of a mild aromatic C-H activation effected by a copper(II) center ligated in a triazamacrocylic ligand, affording equimolar amounts of a Cu(III)-aryl species and Cu(I) species as reaction products. At low temperatures the Cu(II) complex 1 forms a three-center, three-electron C-H...Cu(II) interaction, identified by pulse electron paramagnetic resonance spectroscopy and supported by density functional theory calculations. C-H bond cleavage is coupled with copper oxidation, as a Cu(III)-aryl product 2 is formed. This reaction proceeds to completion at 273 K within minutes through either a copper disproportionation reaction or, alternatively, even faster with 1 equiv of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), quantitatively yielding 2. Kinetic studies of both reactions strongly implicate a rate-limiting proton-coupled electron transfer as the key C-H activation step, a mechanism that does not conform to the C-H activation mechanism in a Ni(II) analogue or to any previously proposed C-H activation mechanisms.

PULSED FIELD GRADIENTS : A NEW TOOL FOR ROUTINE NMR

A complete review of 1D and 2D gradient‐based NMR experiments published since 1990 is provided. The ease of implementation and the excellent and reproducible results obtained from such experiments offer a powerful tool for the study of molecular structures and dynamics. Thus, when sufficient sample concentration is available, ultra‐clean spectra are obtained in very short acquisition times, making the experiments suitable for automated data acquisition. For these reasons, the concept of routine NMR work for chemists has been dramatically changed in the last few years and, with the correct choice of the experiments to be performed, a large number of chemical questions can be resolved in considerably reduced times. However, sensitivity and resolution are dependent on where the PFGs are incorporated into the pulse sequences and, therefore, these two important factors need to be considered in highly demanding applications. Illustrative examples of the most interesting applications to typical organic compounds are given. ©1998 John Wiley & Sons, Ltd.

Asymmetric Self- and Cross-Aldol Reactions of Glycolaldehyde Catalyzed by D-Fructose-6-phosphate Aldolase†

Aldol additions are key chemical reactions for the construction of chiral complex polyhydroxylated molecules. Recent developments in direct aldol additions using bio-, organo-, and metal catalysts are promising since these methodologies do not require separate generation of enolate equivalents and thus improve the atom economy of the transformation. 2,5–8] Aldehydes have been regarded as highly interesting donors in aldol reactions, because the products formed are themselves aldehydes that can be used in further aldol additions for the construction of complex polyfunctional molecular frameworks. Hence, the direct catalytic cross-aldol reaction of aldehydes constitutes a challenge for these methodologies. 10] Selfand cross-aldol reactions were achieved by organocatalysis in N,N-dimethylformamide (DMF) using simple aliphatic and aromatic aldehydes. Selfand cross-aldol additions involving glycolaldehyde derivatives are of paramount interest because they allow access to polyol architectures. 13] Organocatalytic selfand cross-aldol additions of free glycolaldehyde failed to provide promising results. 16] A successful self-aldol addition was accomplished in DMF, but it was limited to glycolaldehyde derivatives with electron-rich a-alkyloxy or bulky asilyloxy protecting groups. No further additions were observed on the corresponding aldol adducts, a feature essential for a two-step aldol-based synthesis of carbohydrates. This approach was used to prepare protected hexoses: a direct organocatalytic self-aldol addition was followed by a direct metal-catalyzed aldol addition. In cross-aldol additions, the organocatalyst cannot selectively control the donor and acceptor roles; this is governed by the aldehyde structure and reactivity. Therefore, in the presence of simple aliphatic aldehyde donors 13] O-protected glycolaldehyde derivatives act invariably as acceptors, likely because they are kinetically disfavored as donors. Biocatalytic synthetic strategies for carbohydrates and their analogues require water-soluble polyhydroxyaldehyde derivatives as acceptor substrates for aldolases. 20] Multistep strategies have suffered from the laborious and costly isolation of sensitive deprotected hydroxyaldehydes which are usually obtained by chemical means. In addition, the vast majority of reported biocatalytically prepared carbohydrates and related products are ketoses. This is because aldolases specific for aldose-type sugars are scarce in nature; 2-deoxyribose-5-phosphate aldolase (DERA) is a notable exception and actually functions as a deoxysugar aldolase. Hence, cross-aldol reactions of aldehydes have been a limited field for biocatalysis, and DERA is the only enzyme known to catalyze the stereoselective cross-aldol addition of acetaldehyde to other aldehydes. However, the low conversion rates of this enzyme with non-phosphorylated, unnatural substrates and its inability to generate two consecutive hydroxylated positions with each newly formed bond limit considerably its scope of applicability. Consequently, the biocatalytic selfand cross-aldol additions of glycolaldehyde are a challenge for the cascade two-step synthesis of carbohydrates. Recently, we reported the synthesis of iminosugars and other polyhydroxylated compounds catalyzed by d-fructose6-phosphate aldolase (FSA). This aldolase shows an unprecedented tolerance for donor substrates such as dihydroxyacetone (DHA), hydroxyacetone (HA), and 1-hydroxy2-butanone. In the course of our investigations on the catalytic properties of FSA, we discovered a new and unexpected activity of paramount importance: its ability to catalyze the direct stereoselective self-aldol addition of glycolaldehyde (GA) (1) to furnish d-( )-threose (2) (Scheme 1). In this reaction, GA (1) acts as both the

Full sensitivity and enhanced resolution in homodecoupled band-selective NMR experiments.

Chemical shifts and coupling constants (J) are fundamentals in the analysis and interpretation of NMR spectra. Multiplicity information and J values can be extracted from the analysis of the fine multiplet structure, and they can be related to structural parameters, such as the number of neighbouring spins, the trace of trough-bond connectivities or dihedral angle constraints. Over recent years, a significant interest has emerged to develop homodecoupled H NMR spectroscopy techniques that offer increased resolution by simplifying the homonuclear splitting pattern, and therefore reducing signal overlapping. The simplest approach for homodecoupling is the use of semiselective shaped pulse decoupling during signal detection, where the receiver and the decoupling are alternatively activated. If the semiselective pulse is applied in a region A of the spectrum, the multiplet structure of J coupled signals resonating in a different region B appear simplified while they are detected. However, this is not a broadband method because protons from a third region C would not be decoupled, and therefore the corresponding coupling splittings will remain in the partially decoupled spectrum. Although the use of sophisticated multiple-region decoupling using different and simultaneous decoupling waveforms could be applied, it is difficult to achieve a perfect decoupling for all resonances and, moreover, without the interference of undesired decoupling sidebands. Alternatively, the internal projection in the chemical shift dimension of J-resolved experiments or the diagonal signals in anti-z-COSY experiments have been also proposed to obtain broadband homodecoupled NMR spectra. They require the collection of more time consuming 2D/3D data and post-processing tasks can be further required. Some years ago, the so-called Zangger–Sterk (ZS) method based on the implementation of the spatially encoded concept along the z-dimension was also proposed. The ZS method has been further refined and several applications have been reported to obtain high-resolved pure-shift multidimensional NMR spectra. The main drawbacks of ZS methods are their low sensitivities because signal only comes from selected z slices and, on the other hand, the need for an FID reconstruction method by means of a time-consuming 2D/3D mode acquisition. Very recently, a new NMR detection scheme has been proposed for the instant and speed-up acquisition of ZS-decoupled spectra in a one-shot single-scan experiment. The instant technique greatly improves the sensitivity per time unit ratio although the attainable sensitivity is still far from a regular H spectrum. Analogous ZS methods incorporating isotopic C editing by using BIRD elements have been also reported to efficiently minimise the effects of strong coupling, but an important penalty in sensitivity remains due to the low natural abundance of C (1.1 %). Based on the instant ZS experiment, a novel NMR spectroscopy method for the fast acquisition of full-sensitive, homodecoupled band-selective (HOBS) NMR spectra is proposed here. It is noteworthy that the spatial encoding gradients applied simultaneously with the selective pulses in the original instant scheme are here omitted, avoiding sensitivity losses due to spatial slice selection. In addition, the HOBS method incorporates a number of advantages, such as: 1) an effective homodecoupling NMR block consisting of a pair of hard/selective 1808 pulses flanked by pulsed field gradients (Figure 1), 2) an excellent spectral quality related to the use of selective gradient echoes, 3) real-time data collection without need of additional reconstruction methods that also allows conventional FID data processing, and 4) an easy implementation in multidimensional experiments. In our hands, the best results in terms of selectivity and optimum

D-Fructose-6-phosphate Aldolase in Organic Synthesis: Cascade Chemical-Enzymatic Preparation of Sugar-Related Polyhydroxylated Compounds

Novel aldol addition reactions of dihydroxyacetone (DHA) and hydroxyacetone (HA) to a variety of aldehydes catalyzed by D-fructose-6-phosphate aldolase (FSA) are presented. In a chemical-enzymatic cascade reaction approach, 1-deoxynojirimycin and 1-deoxymannojirimycin were synthesized starting from (R)- and (S)-3-(N-Cbz-amino)-2-hydroxypropanal, respectively. Furthermore, 1,4-dideoxy-1,4-imino-D-arabinitol and 1,4,5-trideoxy-1,4-imino-D-arabinitol were prepared from N-Cbz-glycinal. 1-Deoxy-D-xylulose was also synthesized by using HA as the donor and either 2-benzyloxyethanal or 2-hydroxyethanal as acceptors. In both cases the enzymatic aldol addition reaction was fully stereoselective, but with 2-hydroxyethanal 17 % of the epimeric product at C2, 1-deoxy-D-erythro-2-pentulose, was observed due to enolization/epimerization during the isolation steps. It was also observed that D-(-)-threose is a good acceptor substrate for FSA, opening new synthetic possibilities for the preparation of important novel complex carbohydrate-related compounds from aldoses. To illustrate this, 1-deoxy-D-ido-hept-2-ulose was obtained stereoselectively by the addition of HA to D-(-)-threose, catalyzed by FSA. It was found that the reaction performance depended strongly on the donor substrate, HA being the one that gave the best conversions to the aldol adduct. The examples presented in this work show the valuable synthetic potential of FSA for the construction of chiral complex polyhydroxylated sugar-type structures.

Broadband 1H homodecoupled NMR experiments: recent developments, methods and applications

In recent years, a great interest in the development of new broadband 1H homonuclear decoupled techniques providing simplified JHH multiplet patterns has emerged again in the field of small molecule NMR. The resulting highly resolved 1H NMR spectra display resonances as collapsed singlets, therefore minimizing signal overlap and expediting spectral analysis. This review aims at presenting the most recent advances in pure shift NMR spectroscopy, with a particular emphasis to the Zangger–Sterk experiment. A detailed discussion about the most relevant practical aspects in terms of pulse sequence design, selectivity, sensitivity, spectral resolution and performance is provided. Finally, the implementation of the different reported strategies into traditional 1D and 2D NMR experiments is described while several practical applications are also reviewed. Copyright

Enantioselective hydroformylation by a Rh-catalyst entrapped in a supramolecular metallocage

Regio- and enantioselective hydroformylation of styrenes is attained upon embedding a chiral Rh complex in a nonchiral supramolecular cage formed from coordination-driven self-assembly of macrocyclic dipalladium complexes and tetracarboxylate zinc porphyrins. The resulting supramolecular catalyst converts styrene derivatives into aldehyde products with much higher chiral induction in comparison to the nonencapsulated Rh catalyst. Spectroscopic analysis shows that encapsulation does not change the electronic properties of the catalyst nor its first coordination sphere. Instead, enhanced enantioselectivity is rationalized by the modification of the second coordination sphere occurring upon catalyst inclusion inside the cage, being one of the few examples in achieving an enantioselective outcome via indirect through-space control of the chirality around the catalyst center. This effect resembles those taking place in enzymatic sites, where structural constraints imposed by the enzyme cavity can impart stereoselectivities that cannot be attained in bulk. These results are a showcase for the future development of asymmetric catalysis by using size-tunable supramolecular capsules.

Opposite metabolic responses of shoots and roots to drought

Shoots and roots are autotrophic and heterotrophic organs of plants with different physiological functions. Do they have different metabolomes? Do their metabolisms respond differently to environmental changes such as drought? We used metabolomics and elemental analyses to answer these questions. First, we show that shoots and roots have different metabolomes and nutrient and elemental stoichiometries. Second, we show that the shoot metabolome is much more variable among species and seasons than is the root metabolome. Third, we show that the metabolic response of shoots to drought contrasts with that of roots; shoots decrease their growth metabolism (lower concentrations of sugars, amino acids, nucleosides, N, P, and K), and roots increase it in a mirrored response. Shoots are metabolically deactivated during drought to reduce the consumption of water and nutrients, whereas roots are metabolically activated to enhance the uptake of water and nutrients, together buffering the effects of drought, at least at the short term.

High‐Quality 1D Spectra by Implementing Pulsed‐Field Gradients as the Coherence Pathway Selection Procedure

This review covers several high‐resolution NMR methods, including selective excitation, gradient selection and inverse spectroscopy. In this way, clean 1D spectra can be quickly obtained without extreme stability conditions because the classical difference spectroscopy is not involved. In addition, accurate NMR parameters can be easily extracted from such spectra in short measuring times, with high digital resolution and minimum data storage. For these reasons, these 1D experiments are a very useful alternative to multi‐dimensional experiments in structural and/or conformational studies of small‐ and medium‐sized molecules when a limited amount of information is desired. All these experiments are described using the shift operator formalism in order to predict a suitable gradient ratio that rephases the desired magnetization and to analyse the inherent sensitivity losses due to the gradient selection procedure compared with the conventional phase cycle procedure.