Luis F. Veiros

Divergent Coupling of Alcohols and Amines Catalyzed by Isoelectronic Hydride Mn(I) and Fe(II) PNP Pincer Complexes.

Herein, we describe an efficient coupling of alcohols and amines catalyzed by well-defined isoelectronic hydride Mn(I) and Fe(II) complexes, which are stabilized by a PNP ligand based on the 2,6-diaminopyridine scaffold. This reaction is an environmentally benign process implementing inexpensive, earth-abundant non-precious metal catalysts, and is based on the acceptorless alcohol dehydrogenation concept. A range of alcohols and amines including both aromatic and aliphatic substrates were efficiently converted in good to excellent isolated yields. Although in the case of Mn selectively imines were obtained, with Fe-exclusively monoalkylated amines were formed. These reactions proceed under base-free conditions and required the addition of molecular sieves.

Gold-Catalyzed Synthesis of Furans and Furanones from Sulfur Ylides

Scheme 1 reveals a notable incidence of 3-carboxy-functionalized polysubstituted furans in the natural product cores, including furofuranone and -pyranone moieties (such as in angelone). Herein we report a simple and flexible gold-catalyzed synthesis of densely functionalized 3-carboxyfuran derivatives that hinges on a key cross-coupling between sulfonium ylides and alkynes. We further disclose an intriguing reactivity switch that allows the synthesis of furanones containing a quaternary center as well as computational data on the mechanism of these transformations. Initial studies focused on the alkynyl sulfonium ylide 1a, readily available by direct ylide transfer to the corresponding ketoester. Exposure of this compound to diverse gold(I) promoters led to sharply contrasting results (see the Supporting Information for details), and it was found that the simple combination of commercially available PPh3AuCl and AgSbF6 led to quantitative conversion into the furofuranone 2a at room temperature within 3 h. We then examined the scope of this simple yet highly effective procedure for the intramolecular preparation of bicyclic furans. Importantly, all the alkynyl sulfonium ylides employed as substrates could be readily accessed by direct ylide transfer in very high yields according to our previously reported procedure. Their stability towards chromatography and recrystallization along with their crystallinity renders them easily handled substrates for subsequent transformations. As shown in Table 1, a variety of bicyclofurans could be readily prepared by simply stirring the ylide precursors in the presence of the gold catalyst at room temperature. Importantly, the preparation of the furopyranone 2 i (Table 1, entry 9) required slightly modified conditions and the use of a different, more electron-poor phosphine, once again suggesting that less facile cyclizations of sulfonium ylides onto alkynes may be favored by the use of more electrondeficient gold(I) species. Various alkyl and aryl moieties were tolerated by the procedure, and furopyrrolones such as 2k could also be prepared by employing an amide-tethered alkyne. All-carbon tethers are also suitable for this transformation (Table 1, entry 12). To the best of our knowledge, this constitutes the first intramolecular synthesis of furans from stabilized sulfonium ylides. We then turned our interest to an intermolecular version of the same reaction. The double stabilization of our sulfonium ylides made some optimization of this process necessary, and some key results obtained are compiled in Scheme 2. The use of tBuXPhos as a ligand was required to obtain synthetically useful yields of product 5 a, particularly with regard to preventing excessive polymerization of phenylacetylene (4a ; Scheme 2a). The very high regioselectivity of this reaction is noteworthy, as only trace amounts of other regioisomers could be detected. Additionally, and in complementary fashion to the recent elegant report by Skyrdstrup et al. employing singly stabilized sulfonium ylides, we Scheme 1. Selected examples of natural products containing a furan core.

Iminoboronates: a new strategy for reversible protein modification.

Protein modification has entered the limelight of chemical and biological sciences, since, by appending small molecules into proteins surfaces, fundamental biological and biophysical processes may be studied and even modulated in a physiological context. Herein we present a new strategy to modify the lysines ε-amino group and the proteins N-terminal, based on the formation of stable iminoboronates in aqueous media. This functionality enables the stable and complete modification of these amine groups, which can be reversible upon the addition of fructose, dopamine, or glutathione. A detailed DFT study is also presented to rationalize the observed stability toward hydrolysis of the iminoboronate constructs.

Ring slippage in indenyl complexes: structure and bonding

Abstract A review of some structural and reactivity aspects of the coordinated indenyl ligand, dealing mainly with the systems theoretically studied by the authors is presented. In the first section, the structural characterization of η5 and η3 indenyl is attempted, noticing that the nodal properties of the π orbitals of the indenyl prevent a totally symmetric coordination in a η5-indenyl. The two bonds to the hinge carbon atoms are always longer, and the distance becomes longer than a M–C bond in the η3-indenyl derivatives. Some intermediate distances are found in [(Ind)2Ni] where, formally, the ligand is halfway between η5 and η3. The ring slippage occurs when two electrons are added to the system, occupying a metal–indenyl antibonding orbital, which becomes more stable upon folding. We reviewed electrochemical and ligand addition driven slippage, in the second section. A comparison with the behavior of the cyclopentadienyl ligand was attempted in the end.

Efficient Hydrogenation of Ketones and Aldehydes Catalyzed by Well-Defined Iron(II) PNP Pincer Complexes: Evidence for an Insertion Mechanism

We have prepared and structurally characterized a new class of Fe(II) PNP pincer hydride complexes [Fe(PNP-iPr)(H)(CO)(L)]n (L = Br–, CH3CN, pyridine, PMe3, SCN–, CO, BH4–; n = 0, +1) based on the 2,6-diaminopyridine scaffold where the PiPr2 moieties of the PNP ligand are connected to the pyridine ring via NH and/or NMe spacers. Complexes [Fe(PNP-iPr)(H)(CO)(L)]n with labile ligands (L = Br–, CH3CN, BH4–) and NH spacers are efficient catalysts for the hydrogenation of both ketones and aldehydes to alcohols under mild conditions, while those containing inert ligands (L = pyridine, PMe3, SCN–, CO) are catalytically inactive. Interestingly, complex [Fe(PNPMe-iPr)(H)(CO)(Br)], featuring NMe spacers, is an efficient catalyst for the chemoselective hydrogenation of aldehydes. The first type of complexes involves deprotonation of the PNP ligand as well as heterolytic dihydrogen cleavage via metal-alkoxide cooperation, but no reversible aromatization/deprotonation of the PNP ligand. In the case of the N-methylated complex the mechanism remains unclear, but obviously does not allow bifunctional activation of dihydrogen. The experimental results complemented by DFT calculations strongly support an insertion of the C=O bond of the carbonyl compound into the Fe–H bond.

Fast and Highly Regioselective Allylation of Indole and Pyrrole Compounds by Allyl Alcohols Using Ru-Sulfonate Catalysts

New Ru-sulfonate catalysts have been synthesized and shown to very rapidly allylate indole and pyrrole compounds using allyl alcohols as substrates. The observed regioselectivity is exceptionally high (up to 100% of the branched isomer). Density functional theory calculations explain these results.

Axial coordination of NHC ligands on dirhodium(II) complexes: Generation of a new family of catalysts

An efficient new methodology for the arylation of aldehydes is disclosed which uses dirhodium(II) catalysts and N-heterocyclic carbene (NHC) ligands. Complexes of Rh 2(OAc) 4 with one and two NHCs attached on the axial positions were successfully isolated, fully characterized, and used as catalysts in the reaction. The saturated monocomplex ((NHC 5)Rh 2(OAc) 4) 31 was shown to be the most active catalyst and was particularly efficient in the arylation of alkyl aldehydes. DFT calculations support participation of complexes with one axial NHC in the reaction as the catalysts active species and indicate that hydrogen bonds involving dirhodium unit, reactants, and solvent (alcohol) play an important role on the reaction mechanism.

Heterolytic Cleavage of Dihydrogen by an Iron(II) PNP Pincer Complex via Metal–Ligand Cooperation

The bis-carbonyl Fe(II) complex trans-[Fe(PNP-iPr)(CO)2Cl]+ reacts with Zn as reducing agent under a dihydrogen atmosphere to give the Fe(II) hydride complex cis-[Fe(PNP-iPr)(CO)2H]+ in 97% isolated yield. A crucial step in this reaction seems to be the reduction of the acidic NH protons of the PNP-iPr ligand to afford H2 and the coordinatively unsaturated intermediate [Fe(PNPH-iPr)(CO)2]+ bearing a dearomatized pyridine moiety. This species is able to bind and heterolytically cleave H2 to give cis-[Fe(PNP-iPr)(CO)2H]+. The mechanism of this reaction has been studied by DFT calculations. The proposed mechanism was supported by deuterium labeling experiments using D2 and the N-deuterated isotopologue of trans-[Fe(PNP-iPr)(CO)2Cl]+. While in the first case deuterium was partially incorporated into both N and Fe sites, in the latter case no reaction took place. In addition, the N-methylated complex trans-[Fe(PNPMe-iPr)(CO)2Cl]+ was prepared, showing no reactions with Zn and H2 under the same reaction conditions. An alternative synthesis of cis-[Fe(PNP-iPr)(CO)2H]+ was developed utilizing the Fe(0) complex [Fe(PNP-iPr)(CO)2]. This compound is obtained in high yield by treatment of either trans-[Fe(PNP-iPr)(CO)2Cl]+ or [Fe(PNP-iPr)Cl2] with an excess of NaHg or a stoichiometric amount of KC8 in the presence of carbon monoxide. Protonation of [Fe(PNP-iPr)(CO)2] with HBF4 gave the hydride complex cis-[Fe(PNP-iPr)(CO)2H]+. X-ray structures of both cis-[Fe(PNP-iPr)(CO)2H]+ and [Fe(PNP-iPr)(CO)2] are presented.

C−H Activation of Acetonitrile at Nickel: Ligand Flip and Conversion of N-Bound Acetonitrile into a C-Bound Cyanomethyl Ligand

Nickel joins the fairly exclusive list of metals that can activate nitrile C-H bonds. We report the first example of the C-H activation of an acetonitrile ligand on a nickel center. The acetonitrile ligand formally loses a proton and undergoes a sharp flip to give a cyanomethyl ligand that is coordinated to the nickel atom. Structures of an initial N-bound acetonitrile-nickel complex and of a final cyanomethyl-nickel complex are both presented.

Highly Efficient and Selective Hydrogenation of Aldehydes: A Well-Defined Fe(II) Catalyst Exhibits Noble-Metal Activity

The synthesis and application of [Fe(PNPMe-iPr)(CO)(H)(Br)] and [Fe(PNPMe-iPr)(H)2(CO)] as catalysts for the homogeneous hydrogenation of aldehydes is described. These systems were found to be among the most efficient catalysts for this process reported to date and constitute rare examples of a catalytic process which allows selective reduction of aldehydes in the presence of ketones and other reducible functionalities. In some cases, TONs and TOFs of up to 80000 and 20000 h–1, respectively, were reached. On the basis of stoichiometric experiments and computational studies, a mechanism which proceeds via a trans-dihydride intermediate is proposed. The structure of the hydride complexes was also confirmed by X-ray crystallography.