Institut de Chimie Moléculaire de Paris : organique, inorganique et biologique

Functionalization via covalent grafting of organic functions allows to tune the redox and acid-base properties, and the solubility of polyoxometalates, to enhance their stability and biological activity and to reduce their toxicity, to facilitate their implementation in extended structures and functional devices. We discuss herein the electronic and binding connections, and the various synthesis methodologies. We emphasize on organonitrogen, organosilyl and organophosphonyl derivatives with special attention to synthesis, characterization and potential applications in catalysis and materials science. We also consider the giant molybdenum oxide-based clusters especially the porous capsule-type clusters (Keplerates) which have high relevance to this context.

Since Ellman's seminal works, over the past ten years tert-butanesulfinimines have proved to be useful chiral amino intermediates for organic synthesis. Through highly stereoselective reactions, amongst which reductions, nucleophilic 1,2-additions and ylide condensations, a broad range of nitrogen-containing compounds has been synthesized. Although the stereoselectivity levels are high in most cases, the sense of the stereoinduction is generally not predictable. The object of this critical review is to present the models proposed to rationalize the stereochemical outcome of the reactions involving tert-butanesulfinimines and to point out an obvious lack of homogeneity amongst them (128 references).

Calculations suggest that complexes of borane with N-heterocyclic carbenes (NHC) have B-H bond dissocation energies more then 20 kcal/mol less than free borane, diborane, borane-THF, and related complexes. Values are in the range of popular radical hydrogen atom donors like tin hydrides (70-80 kcal/mol). The resulting prediction that NHC borane complexes could be used as radical hydrogen atom donors was verified by radical deoxygenations of xanthates by using either AIBN or triethylborane as initiator.

This tutorial review aims at presenting recent contributions dealing with organic chemistry of organophosphorus radicals. The first part briefly lays out the physical organic background of such intermediates. In a second part the use of organophosphorus radicals possessing a P-H bond that can undergo homolytic cleavage as alternative mediators is detailed. The third part is focused on radical additions of phosphorus-centered radicals to unsaturated compounds, an old reaction that is being rejuvenated. Lastly, radical eliminations of phosphorus-centered radical are introduced in the fourth part. Most of the latter are relatively novel reactions, and have never been reviewed previously.

[reaction: see text] A polymer-supported catalyst for Huisgen's [3+2] cycloaddition reaction between azides and alkynes was prepared from copper(I) iodide and Amberlyst A-21. This catalyst was then used in an automated synthesis of 1,4-disubstituted 1,2,3-triazoles giving access to these products in good yields. The catalyst has shown good activity, stability, and recycling capabilities.

For many years, our research group has been interested in the new developments of cobalt-mediated cyclizations. In this article, our recent achievements in the field of inter- and intramolecular [2 + 2 + 2] cyclizations are compiled.

Round and round it goes: Propargylic esters are versatile substrates for Au-based catalysts. However, under typical conditions the starting Au-coordinated propargylic ester 1 is in rapid equilibrium with the gold vinylic carbenoid species 2 and with gold allene species 3. A number of factors dictate which intermediate is lower in energy and which type of products form.

Cyclopentenylidene gold complexes can easily be formed from vinyl allenes through a Nazarov-like mechanism. Such carbenes may transform in four different ways into polycyclic frameworks: electrophilic cyclopropanation, C-H insertion, C-C migration, or proton shift. We have studied the selectivity of these different pathways and used our findings for the expedient preparation of valuable complex molecules. An application to the total synthesis of a natural product, Delta(9(12))-capnellene, is presented. DFT computations were carried out to shed light on the mechanisms.

It's a trap! Both epoxides and aziridines substituted by an aryl ketone can be reduced efficiently using visible-light photoredox catalysts. The radicals generated were trapped by allyl sulfones, and formed α-branched β-hydroxy or amino derivatives with high diastereocontrol (see scheme; dtbbpy=4,4′-di-tert-butyl-2,2′-bipyridine, ppy=2-phenylpyridine). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract The increasing use of polyoxometalates in the fields of material sciences, catalysis, and biology has raised the interest in chirality of such systems. This review provides a summary of the different strategies followed: i) chirality in solid‐state arrangements, ii) chiral polyoxometalate frameworks, and iii) chiral polyoxometalate–organic hybrids. Through the discussion of selected examples, an outline for future work is drawn. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

We have developed an expedient method for the synthesis of polycyclic compounds from propargyl acetates or vinyl allenes involving up to three Au(I)-catalyzed elemental steps: 3,3-rearrangement, metalla-Nazarov reaction, and electrophilic cyclopropanation. The reaction proceeds under very mild conditions and in short times. The mechanism has been studied by DFT computations.

To understand some experimental data at odds with the computed mechanism of the CpCo(L2)-catalyzed [2 + 2 + 2] cyclotrimerization of ethyne, DFT computations were carried out following the fate of methyl- and hydroxycarbonyl-substituted alkynes to give the corresponding arenes. The key intermediate in all cases is a triplet cobaltacyclopentadiene obtained by oxidative coupling of the corresponding CpCo(bisalkyne) complex and subsequent spin change via a minimum energy crossing point (MECP). From that species, two different catalytic cycles lead to an arene product, depending on the nature of the alkyne and other ligands present: either alkyne ligation to furnish a cobaltacyclopentadiene(alkyne) intermediate or trapping by a sigma-donor ligand to generate a coordinatively saturated cobaltacyclopentadiene(PR3) complex. The former leads to the CpCo-complexed arene product via intramolecular cobalt-assisted [4 + 2] cycloaddition, whereas the latter may, in the case of a reactive dienophile (butynedioic acid), undergo direct intermolecular [4 + 2] cycloaddition to generate a cobaltanorbornene. The bridgehead cobalt atom is then reductively eliminated after another change in spin state from singlet to triplet. The necessary conditions for one or the other mechanistic pathway are elaborated.

Chloride ligands are crucial in the gold-catalyzed cycloisomerization of allenynes to give hydrindienes such as 1, which are formally products of CH activation and formed completely selectively over the usual Alder-ene products (2; see scheme). This effect could be rationalized by a DFT study that sheds new light on the electrophilic metal-catalyzed cycloisomerization of polyunsaturated systems. Electrophilic metal halides, also referred to as π Lewis acids, are exquisite catalysts for the selective and efficient cycloisomerization of polyunsaturated precursors into highly valuable carbo- or heterocyclic derivatives.1 The diversity of the substrates that have been examined, mainly under platinum(II) and (IV) catalysis,2 as well as gold(I) and (III) catalysis,3 not only illustrates the versatility of these processes, but also renders the proposed mechanistic scenarios more plausible. In the case of enynes,4 electrophilic activation of the alkyne triggers a nucleophilic attack by the alkene to give a metallacyclopropyl carbene intermediate that can evolve along different pathways.5 Alternatively, metallacyclopentene intermediates have been invoked to give Alder-ene types of products.6 In this context, because of their high degree of unsaturation, allenynes are very interesting substrates.7 Our initial experiments with PtCl2 and precursors 1 (Tables 1 and 2) gave three types of reaction evolution depending upon the substitution pattern of the starting material.8 To rationalize the formation of products 2–4, we proposed the intervention of a common platinacyclopentene intermediate. This suggestion was later supported by the DFT calculations of Soriano and Marco-Contelles.9 Nevertheless, some new data did not completely fit with this mechanistic rationale. For example, we noticed that the formation of hydrindiene 2 a from 1 a could also be promoted by PtCl4 (Table 1, entry 2) in a more rapid reaction than that with PtCl2; this result would imply an unlikely PtIV–PtVI catalytic couple if a platinacyclopentene pathway were involved (Table 1, entry 2).10 Furthermore, although, to the best of our knowledge, auracyclopentenes are unknown species, gold(III) and gold(I) chloride catalysts also afforded hydrindienes 2 a and 2 b in high yield and after short reaction times at 0 °C (Table 1, entries 3–5 and 9). Two other observations shed additional light on this transformation. In the presence of a cationic gold(I) complex generated in situ from the reaction of [AuCl(PPh3)] with AgSbF6, a dramatic change in reactivity occurred, and only the regioisomers 3 were isolated (Table 1, entry 6). This reactivity was further confirmed when we used [Au(PPh3)NTf2]11 and [Pt(PhCN)2dppp](BF4)212 (dppp=1,3-bis(diphenylphosphanyl)propane, two other cationic halide-free metal catalysts (Table 1, entries 7–8). In general, alkynes with a trimethylsilyl (TMS) substituent react sluggishly in PtCl2-catalyzed processes.13 Accordingly, allenyne 1 c did not react under AuCl3 or AuCl catalysis (Table 1, entries 10–11). When a gold(I) source was used instead, a complex mixture of unidentified products resulted (Table 1, entry 12).14 In contrast, unambiguous reactivity was observed for precursor 1 d in the presence of the previously used catalysts (Table 2). In all cases, vinyl allene 4 was formed in high yield. Entry Catalyst Conditions 2 [%] 3 [%] exo/endo 1 a: R1=R2=H 1 PtCl2, 5 mol % toluene, RT, 24 h 80 –[b] – 2 PtCl4, 5 mol % toluene, RT, 1 h 80 –[b] – 3 AuCl3, 1 mol % CH2Cl2, 0 °C, 0.5 h 80 –[b] – 4 NaAuCl4, 1 mol % CH2Cl2, 0 °C, 1 h 75 –[b] – 5 AuCl, 1 mol % CH2Cl2, 0 °C, 0.5 h 79 –[b] – 6 [Au(PPh3)SbF6], 1 mol % CH2Cl2, 0 °C, 0.25 h 0 70 1:1 7 [Au(PPh3)NTf2], 1 mol % CH2Cl2, 0 °C, 6 h 5 68 2:1 8 [Pt(PhCN)2dppp](BF4)2, 5 mol % CH2Cl2, 35 °C, 0.3 h –[b] 57 3:1 1 b: R1=Me, R2=H 9 AuCl3, 1 mol % CH2Cl2, 0 °C, 0.5 h 64[c] –[b] – 1 c: R1=H, R2=SiMe3 10 AuCl3, 1 mol % CH2Cl2, 0 °C to RT no reaction 11 AuCl, 1 mol % CH2Cl2, 0 °C to RT no reaction 12 [Au(PPh3)SbF6], 1 mol % CH2Cl2, 0 °C, 0.25 h complex mixture of isomers Entry Catalyst Conditions 4 [%] 1 PtCl2, 5 mol % toluene, RT, 24–48 h 84 2 AuCl3, 1 mol % CH2Cl2, RT, <5 min 92 3 AuCl, 1 mol % CH2Cl2, RT, <5 min 89 4 [Au(PPh3)SbF6], 1 mol % CH2Cl2, RT, <5 min 79 As no metallacyclic pathway could explain these new findings with gold, we suspected the occurrence of a cationic event.15 To probe this hypothesis, we monitored the reaction of 1 a in CD3OD in the presence of AuCl3 (1 mol %) by 1H and 13C NMR spectroscopy. The conversion of 1 a was complete within 10 minutes, and compound 5 was formed as a single diastereomer (Scheme 1). The stereochemical assignment of the exocyclic double bond was based on an NOE experiment. The structure of compound 5 supports the existence of a carbocationic intermediate in which the carbon–gold bond is anti to the cationic center. Trapping of a key intermediate with deuterated methanol. We also wanted to probe the occurrence of a cationic route in non-oxygenated solvents. Echavarren and co-workers showed that a metallacyclic pathway can be disfavored artificially in the presence of oxygen-containing nucleophilic solvents.6 Therefore, we introduced a phenyl group at the internal allene position to give 1 e (Table 3). This substrate proved to be highly reactive and provided in good yield the expected Friedel–Crafts product 6 with an exocyclic methylene group, accompanied by the endocyclic isomers 7 and 8.16 In the presence of platinum(II) the reaction was much slower, and a large amount of hydrindiene 2 e was formed. Entry Catalyst Cond. Yield [%] Products Ratio 1 AuCl3, 1 mol % CH2Cl2, 0 °C, 15 min 98 6/7/8 67:27:6 2 [Au(PPh3)SbF6], 1 mol % CH2Cl2, 0 °C, 15 min 87 6/7/8 65:30:5 3 PtCl2, 5 mol % toluene, RT, 30 h 84 2 e/6/7/8 38:44:11:7 We next performed an isotope-labeling experiment with compound [D5]-1 e (Scheme 2). As a result of the facile isomerization of the exocyclic double bond, it was not possible to assign the configuration of compound [D5]-6. However, it was evident from 1H NMR spectroscopy that a deuterium atom had been transferred from the phenyl ring to the exocyclic double bond. Deuterium-transfer experiment. This valuable set of information drove us to analyze the mechanism in more detail. The reactivity of allenynes toward AuPH3+ and AuCl3 was studied by means of DFT computations. AuCl3 was chosen as a unique model for gold halide species since it is assumed to be the dominant catalyst after chloride substitution in AuCl4− or after the dismutation of AuCl into AuCl3 and Au0 in CH2Cl2.17 The latter assertion derives from our observation of a brown powder that forms instantaneously when AuCl is added to a solution of any allenyne. An X-ray powder diffraction study confirmed the presence of pure gold(0) unambiguously (see Supporting Information for details). Along with the results of computational studies dealing with the gold-catalyzed cyclization of enynes,18 we could locate neither auracyclopentenes nor their hypothetical η4-complexed precursors. Instead, cationic species of type B or D (Scheme 3) were found and linked to alkyne–gold complexes A via reasonably low lying transition states (Δ≈5–15 kcal mol−1; see Supporting Information).19 In all cases, exo cyclizations, which lead to a trans arrangement of the C2C7 and C1M bonds, were found to be favored kinetically over endo cyclizations by nearly a factor of two. Mechanistic proposal for the formation of Alder-ene and vinyl allene products: Δ values were calculated at the DFT/B3LYP/LACVP(d,p) level for M=AuCl3 (and AuPH3+). Representative geometries of transition states are given for M=AuPH3+. P (black), Au (dark gray), Cl (light gray). The formation of Alder-ene products C was only computationally possible when R=H, by a direct 1,5-proton shift. These transformations require a free energy of activation of 22.2 kcal mol−1 (AuCl3) or 24.7 kcal mol−1 (AuPH3+) and are exothermic by 27.7 kcal mol−1 (AuCl3) or 25.1 kcal mol−1 (AuPH3+). The formation of vinyl allene E from D (R=Me) is also possible in a single step by a 1,5-hydride shift.20 Free energies of activation of 11.1 kcal mol−1 (AuCl3) and 9.9 kcal mol−1 (AuPH3+) were calculated for these exothermic processes (ΔG298=−5.0 kcal mol−1 (AuCl3) and −6.0 kcal mol−1 (AuPH3+)). To account for the formation of hydrindienes,21 we noticed that only chloride-containing catalysts could promote this specific cycloisomerization (see Table 1).Therefore, we envisaged a mechanism for the transformation of B into I that involves isomerization of the vinyl metal moiety followed by the elimination of HCl. From a thermodynamic point of view, the isomerization of B into G is favorable with AuCl3 (ΔG298=−7.1 kcal mol−1 (R=H) and −7.2 kcal mol−1 (R=Me)), but not with AuPH3+ (ΔG298=3.0 kcal mol−1 (R=H) and 1.5 kcal mol−1 (R=Me)). Manifold efforts failed to locate a transition state corresponding to the direct transformation of B into G. However, we were able to find a two-step mechanism for this isomerization (Scheme 4). When R=H and M=AuCl3 (or AuPH3+), a free energy of activation of 9.0 (11.0) kcal mol−1 is sufficient to convert B into intermediate F, which is more stable than B by 17.8 (13.3) kcal mol−1. In this case, the quite low free energies of activation make this step faster than the 1,5-proton shifts described above. On the other hand, when R=Me (Δ=17.1 kcal mol−1 (AuCl3) and 38.1 kcal mol−1 (AuPH3+)) the 1,5-hydride shift is still the fastest process. Therefore, the rest of the discussion will be restricted to the case R=H. Complexes of type F would result from a formal [2+2] cycloaddition of the starting compounds A.22 Although the C1C8 bond is especially long (≈1.59 Å), ring opening at C1C8 is kinetically difficult. With AuCl3, a free energy of activation of 28.5 kcal mol−1 was found for the endothermic transformation of F into G (ΔG298=10.7 kcal mol−1). However, G would readily undergo elimination of HCl with concomitant formation of an AuC bond to give H (Δ=13.6 kcal mol−1). This step is appreciably exothermic by 22.4 kcal mol−1. Energy profile [kcal mol−1] for the transformation of A (R=H, M=AuCl3) into the hydrindiene precursor I: Geometries of key transition states are depicted. Energy values for the transformation of A into G with M=AuPH3+ are also indicated in parentheses. The resulting alkene–gold complex H could then undergo a 5-endo-trig carboauration to give complex I. This transformation requires quite a high free energy of activation of 27.1 kcal mol−1 but is also characterized by a large exothermicity of 23.3 kcal mol−1. The last step could then be the cleavage of the AuC bond by HCl, to liberate the final product and regenerate the catalyst. Overall, the formation of I from A has a thermodynamic driving force greater than that corresponding to the transformation of A into C (ΔG298(AI)=−73.7 kcal mol−1; ΔG298(AC)=−48.6 kcal mol−1). Thus, with AuCl3, the two-step isomerization of the vinyl metal moiety positions the metal suitably for the elimination of HCl. On the other hand, the isomerization of B into G is much more difficult with AuPH3+. Although the first step to give F can be quite fast (Δ=11.0 kcal mol−1) and thermodynamically favorable (ΔG298=−13.3 kcal mol−1), the energy requirement for the transformation of F into G seems to be prohibitively high (Δ=45.3 kcal mol−1, ΔG298=16.3 kcal mol−1).23 As F was not found to evolve in any other way, we believe that the formation of the Alder-ene product C arises from the 1,5-proton shift described above, despite a higher activation energy (24.7 kcal mol−1 for B→C versus 11.0 kcal mol−1 for B→F). The greater stability of C relative to that of F (ΔG298(AF)=−37.5 kcal mol−1; ΔG298(AC)=−49.3 kcal mol−1) should funnel the reaction toward the Alder-ene product. Thus, gold catalysis has provided deeper insight into the mechanism of the cycloisomerization of allenynes. Because no standard metallacyclic route could be envisaged, two unusual mechanistic pathways which take into account the presence of cationic intermediates have been proposed: a 1,5-proton shift for the Alder-ene products and a 1,5-hydride shift for the vinyl allenes. We also found evidence for an intriguing halide effect that completely alters the cycloisomerization process (Alder-ene versus hydrindiene products), presumably through the elimination of HCl as a key step for the formation of hydrindienes. Finally, physical evidence has been found for the dismutation of AuCl into Au and AuCl3. A comprehensive experimental and computational study will be reported in due course. Dedicated to Professor K. Peter C. Vollhardt on the occasion of his 60th birthday Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z602189_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract After a brief introduction emphasizing the synthetic relevance of the allylic C–H activation step, evoking the first pioneering stoichiometric studies that sowed the “seeds” of this subject, and analyzing similarities and differences between a “classical” and a “direct” Pd‐catalyzed allylation process, this review outlines some selected examples of palladium‐catalyzed direct allylic functionalization. This old reaction, ignored for many years, is now living a new and exciting era.

Catalytic cornerstone: Lanthanide(III) complexes of a lacunary Dawson-type polyoxometalate catalyze Lewis acid mediated reactions (see figure, TMS=trimethylsilyl). The compounds (NBu4)5H2[α1-Ln(H2O)4P2W17O61] (Ln=Yb, Sm, Eu, La) are much more chemoselective than the lanthanide triflates. Furthermore, the polyoxotungstic framework can play a role, presumably through H-bonding to the substrates.

Variants of the CFH gene, encoding complement factor H (CFH), show strong association with age-related macular degeneration (AMD), a major cause of blindness. Here, we used murine models of AMD to examine the contribution of CFH to disease etiology. Cfh deletion protected the mice from the pathogenic subretinal accumulation of mononuclear phagocytes (MP) that characterize AMD and showed accelerated resolution of inflammation. MP persistence arose secondary to binding of CFH to CD11b, which obstructed the homeostatic elimination of MPs from the subretinal space mediated by thrombospsondin-1 (TSP-1) activation of CD47. The AMD-associated CFH(H402) variant markedly increased this inhibitory effect on microglial cells, supporting a causal link to disease etiology. This mechanism is not restricted to the eye, as similar results were observed in a model of acute sterile peritonitis. Pharmacological activation of CD47 accelerated resolution of both subretinal and peritoneal inflammation, with implications for the treatment of chronic inflammatory disease.

Organotrifluoroborates have been oxidized by copper(II) salts and Dess–Martin periodinane via radical intermediates, as evidenced by TEMPO spin-trapping experiments. This new method of radical generation is compatible with functionalization and CC bond formation through Giese-type addition reactions (see scheme; DMSO=dimethyl sulfoxide, TEMPO=2,2,6,6-tetramethyl-1-piperidinyloxyl, free radical). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

As radical chain cascade precursors, N-acylcyanamides give rise to amide–iminyl radicals which, when appropriately substituted, can finally yield pyrroloquinazolines. The versatility of these new radical acceptors is illustrated by the formation of N-heterocycles with wide structural variation and by the total synthesis of luotonin A. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z602940_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The use of N-heterocyclic carbene (NHC) as a ligand in the gold(I)-catalyzed cycloisomerization of enyne results in the assembly of a new carbocyclic product.

Katalytischer Eckstein: Lanthanoid(III)-Komplexe eines lakunaren Dawson-Polyoxometallats wirken als Lewis-Säure-Katalysatoren (siehe Bild, TMS=Trimethylsilyl). Die Verbindungen (NBu4)5H2[α1-Ln(H2O)4P2W17O61] (Ln=Yb, Sm, Eu, La) sind deutlich chemoselektiver als die entsprechenden Lanthanoidtriflate. Darüber hinaus kann das Polyoxowolframat-Gerüst über Wasserstoffbrücken zu den Substraten beteiligt sein. Supporting Information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2006/z600364_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.