Volume 82, Issue 7

The International Conference on Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS) traditionally brings together chemists from industry and academia from all over the world to present and discuss the latest advances in new metal-catalyzed and -mediated reactions, novel preparations and reactions of organometallic reagents, mechanistic insight into important metal-based reactions, and new or improved methods for the synthesis of functional molecules and materials, in which the metal plays a key role. The symposium came to the UK for the first time, following the successful series of OMCOS meetings held in Fort Collins (1981), Dijon (1983), Kyoto (1985), Vancouver (1987), Florence (1989), Utrecht (1991), Kobe (1993), Santa Barbara (1995), Göttingen (1997), Versailles (1999), Taipei (2001), Toronto (2003), Geneva (2005), and Nara (2007). Since Glasgow is the hometown of Peter Pauson, who can be regarded as the founding father of the OMCOS agenda, one can even say that OMCOS came home, after so many years. The symposium was held in the modern Royal Concert Hall in the heart of Glasgow, the largest city in Scotland and the birthplace of the industrial revolution. About 500 participants attended the symposium; particularly large delegations arrived from Japan, Germany, China, and the UK. The symposium program featured 5 plenary lectures, 18 invited lectures, 15 short communications, and one OMCOS Award Lecture (sponsored by Springer Verlag). The topics spanned the broadest area of the OMCOS agenda; particularly interesting was the direct comparison of the two approaches to metathesis, as illustrated by the key players themselves, Profs. Bob Grubbs and Richard Schrock. A number of contributions were focused on C–H activation, which culminated in the lecture delivered by Prof. Keith Fagnou of the University of Ottawa, Canada, the recipient of the OMCOS Award. Those who attended the symposium, as well as the international chemistry community, were then shocked a few months later by learning that this brilliant young scientist became a victim of the swine flu; he will be remembered by all of us. About 350 poster presentations further contributed to this exciting event and highlighted the strength, diversity, and novelty with which this science is being practiced. On the basis of the assessment by a distinguished international jury, 12 posters were selected for OMCOS-15 Poster Awards, sponsored by Springer Verlag. This issue of Pure and Applied Chemistry comprises a collection of 19 papers based on the lectures delivered at OMCOS-15, thereby offering the readers a glimpse of the fascinating chemical achievements communicated at the symposium. The series will continue with OMCOS-16, which will be held in Shanghai, China, 24-28 July 2011, under the chairmanship of Profs. Shengming Ma and Kuiling Ding (www.omcos16.org). Pavel Kočovský Conference Chair

The discovery and development of the asymmetric rhodium-catalyzed [2 + 2 + 2] cycloaddition of alkenyl isocyanates and exogenous alkynes to form indolizinone and quinolizinone scaffolds is described. This methodology has been expanded to include substituted alkenes and dienes, a variety of sterically and electronically diverse alkynes, and carbodiimides in place of the isocyanate. Through X-ray analysis of Rh(cod)/phosphoramidite complexes additives that modify the enantio-determining step, and other experimental data, a mechanism has been proposed that explains lactam, vinylogous amide, and pyridone products and the factors governing their formation. Finally, we have applied this methodology to the synthesis of (+)-lasubine II and (–)-209D.

Cyclizations induced by transition metals such as palladium, platinum, gold, and ruthenium can produce functionalized heterocycles such as 3-(arylmethylene)isoindolones, γ-lactones, and unsaturated δ-lactones.

The efficient synthesis of natural products, drugs, and materials with economical and ecological advantages is a very important goal in modern synthetic chemistry. In such an approach, toxic substrates as well as reagents have to be avoided, the amount of waste has to be reduced, and the exploitation of our resources has to be diminished. In this respect, the use of catalytic processes is highly advantageous; however, even more beneficial is the combination of several catalytic processes either in a sequential or, more efficiently, in a domino mode. In this article, the synthesis of several natural products, drugs, and materials is described, employing multiple Pd-catalyzed processes either in a sequential or a domino fashion. Based on a double-Heck reaction developed by us for the preparation of estradiol, the efficient synthesis of the highly potent contraceptive desogestrel is discussed; for the synthesis of α-tocopherol and diversonol an enantioselective domino-Wacker/Heck reaction was utilized, whereas in the case of diversonol, a domino-Wacker/carbonylation was even more effective, and several molecular switches containing a helical tetrasubstituted double bond were prepared employing a domino-carbopalladation/Stille reaction. Finally, acenaphthylenes could be obtained by a domino-carbopalladation/C–H-activation.

Bis- N -heterocyclic carbenes Pd 0 complexes, Pd 0 (NHC) 2 , are efficient catalysts in Heck reactions performed with aryl bromides or chlorides. The Pd 0 (NHC) 2 that are not stable are generated in situ from Pd II precursors PdY 2 (NHC) 2 (Y = halides) after a chemical reduction. The latter procedure can be mimicked by an electrochemical reduction. The transient Pd 0 (NHC Bn ) 2 is generated by electrochemical reduction of PdY 2 (NHC Bn ) 2 , and its reactivity in oxidative addition to aryl bromides and chlorides is characterized by the same electrochemical technique with the determination of the rate constants. Pd 0 (NHC Bn ) 2 is found to be more reactive than the mixed complex Pd 0 (NHC Bn )(PPh 3 ). Both are the reactive species in an associative mechanism. Comparison with the isolated Pd 0 (NHC t Bu ) 2 reveals that Pd 0 (NHC Bn ) 2 is more reactive than Pd 0 (NHC t Bu ) 2 even if the latter reacts via the mono-carbene Pd 0 (NHC t Bu ) in a dissociative mechanism. This suggests that the formation of mono-carbene Pd 0 (NHC) is not a guarantee for a fast oxidative addition because it is always generated at low concentration in its equilibrium with the related nonreactive bis-carbene Pd 0 (NHC) 2 .

Palladium catalysts allowed for intermolecular direct arylations of heteroarenes with aryl chlorides, tosylates, or mesylates as electrophiles. As an economically attractive alter-native, inexpensive copper catalysts could be employed for regioselective C–H bond aryl-ations of 1,2,3-triazoles. On the contrary, intermolecular C–H bond functionalizations of arenes were accomplished with ruthenium complexes derived from air-stable (heteroatom-substituted) secondary phosphine oxide (HASPO) preligands. Particularly, the use of ruthenium(II) carboxylate complexes enabled broadly applicable direct arylations with inter alia aryl tosylates and phenols, and set the stage for unprecedented intermolecular direct alkylations with unactivated alkyl halides bearing β-hydrogens.

The remarkable versatility of palladium catalysis is exemplified by recent work in two distinct areas. Firstly, coupling chemistry is discussed, in which the reactive entity is generated by cleavage of a C–H or C–Si bond. The second part concerns the activation of allylic C–F bonds, where divergence from the normal stereochemical pattern of the reaction was observed.

Chiral rigid and electron-donating phosphocyclic phosphine ligands and modular atropisomeric biaryl phosphine ligands were designed and synthesized. The performance of these chiral ligands in the asymmetric hydrogenations of prochiral dehydroamino acid derivatives, enamides, imines, keto esters, and ketones has been demonstrated to be excellent.

This account reviews chelation-assisted carbonylation reactions catalyzed by late transition metals. New carbonylation reactions are achieved with these catalysts in the presence of pyridin-2-ylmethanol and pyridin-2-ylmethylamine. The reactions involve activation of O-H and N-H bonds, coordination of the pyridine nitrogen to Rh being essential for the reaction to proceed. In addition, a new type of carbonylation of the ortho C-H bonds in aromatic amides in which the pyridin-2-ylmethylamino moiety functions as a bidentate directing group, is demonstrated. In this reaction, a dinuclear ruthenium complex was isolated from a stoichiometric reaction of amide and Ru 3 (CO) 12 , in which amide binds to one Ru atom in the expected N , N fashion and the carbonyl oxygen binds to the other Ru atom as an O-donor. These studies indicate that chelation methodology is useful for new types of carbonylation reaction, which cannot be achieved by non-chelation systems.

A cationic rhodium(I)/1,1'-bis(diphenylphosphino)ferrocene (dppf) complex catalyzes isomerization of allyl propargyl ethers to allenic aldehydes in good yields at room temperature 40 °C. At 80 °C, carbonyl migration from allenic aldehydes proceeds further to give dienals in good yields. The cationic rhodium(I)/dppf complex acts as a dual catalyst for activation of σ- and π-bonds in these isomerization reactions.

The catalytic asymmetric isomerization of allylic amines to enamines stands out as one of the most accomplished and well-studied reactions in asymmetric catalysis as illustrated by its industrial application. In contrast, the related asymmetric isomerization of primary allylic alcohols to the corresponding aldehydes still constitutes a significant challenge in organic synthesis. Herein, we show that under appropriate reaction conditions, iridium-hydride catalysts promote the isomerization of primary allylic alcohols under very mild reaction conditions. The best catalysts deliver the desired chiral aldehydes with unprecedented levels of enantioselectivity and good yields. Mechanistic hypotheses have been drawn based on preliminary investigations.

A new series of half-sandwich group 8 and 9 metal complexes bearing a metal/NH bifunctional moiety were synthesized from benzylic amines. The isolable Ir amide complexes serve as effective catalysts for aerobic oxidative transformation of secondary and primary alcohols into the corresponding ketones and esters under mild conditions. The aerobic oxidative kinetic resolution of racemic secondary alcohols with chiral bifunctional Ir catalysts was found to proceed smoothly under mild conditions with high selectivity. A novel imido-bridged dirhodium complex, which may be regarded as a dinuclear variant of the bifunctional mononuclear amide complexes, also proved to promote aerobic oxidation of a secondary alcohol and H 2 .

Conjugate addition of Me 3 SiCN to ynones is smoothly catalyzed by Ni(cod) 2 to give β-cyano-silyloxyallenes quantitatively. Subsequent treatment of the silyloxyallenes with N -bromo succinimide (NBS) provides the tetrasubstituted α-bromo-β-cyanoenones in high yields (up to 95 %) with excellent Z -selectivity ( E / Z = up to >1/99). X-ray crystallographic analysis shows a bent structure of the α-bromo-β-cyanoenone due to deconjugation of the π-bond and the carbonyl group. Furthermore, three-component coupling reactions of ynones, dialkylzinc, and alde-hydes are catalyzed by Ni(cod) 2 to provide tetrasubstituted olefins.

A rhenium complex, [ReBr(CO) 3 (thf)] 2 , catalyzed insertion of terminal alkynes into a C–H bond of active methylene sites of 1,3-dicarbonyl compounds. When a catalytic amount of isocyanide or molecular sieves was added to the reaction mixture, the reaction course changed markedly, and insertion of alkynes into a C–C single bond between α- and β-positions of cyclic and acyclic β-keto esters occurred. The formed acyclic δ-keto esters could be converted to 2-pyranones, which were applied to the synthesis of multisubstituted aromatic compounds via the Diels–Alder reaction and successive elimination of carbon dioxide. In the case of the rhenium-catalyzed reactions between terminal alkynes and β-keto esters without substituent at the α-position, tetrasubstituted benzenes were produced regioselectively by two-to-one reaction of the components. The yields of tetrasubstituted benzenes were improved by using a manganese catalyst.

The direct, 100 % atom-economic, and selective synthesis of amines is a challenging task that can be achieved, making use of early transition-metal catalysts. Here we report the synthesis and application of group 4 and 5 high-oxidation-state metal amidate complexes in catalytic C–N (hydroamination) and C–C (hydroaminoalkylation) bond-forming reactions to access substituted amines.

The most familiar gold-catalyzed cyclization pathway for furanyne substrates leads to synthesis of phenols, but new reaction pathways have recently been discovered. The mechanistic background and the synthetic possibilities of these alternative pathways leading to new heterocyclic products are discussed.

The use of the coinage metals copper, silver, and gold enables an efficient and stereo-selective assembly of bioactive heterocycles via allenic intermediates. The synthesis of functionalized allenes by S N 2'-substitution or S N 2'-reduction is mediated or catalyzed by copper, whereas silver and gold are the catalysts of choice for subsequent 5- or 6- endo -cyclizations. Overall, this sequence proceeds with efficient center-to-axis-to-center chirality transfer.

Our development of noble-metal-catalyzed reactions that involve the preparation of sulfur ylides directly from alkynes, without employing sacrificial functionality, is reviewed.

A new methodology for the direct cross-coupling reaction between aryl halides and alkyl halides under iron catalysis is described. Unlike conventional protocols, the direct cross-coupling obviates the need for the preformation of stoichiometric amounts of Grignard species and thus exhibits a reduced hazard potential. The underlying one-pot reaction involves iron-catalyzed Grignard formation followed by a rapid cross-coupling step. Mechanistic data on the role of N , N , N' , N' -tetramethylethylenediamine (TMEDA) as additive, the concentration of intermediates, and the nature of the catalyst species are discussed.

Diiron complexes containing C 3 ligands, such as vinyliminium and vinylalkylidene bridging units, display unusual reaction patterns, not observed when the same organic fragments are bound to a single metal center, or not coordinated. Bridging vinyliminium complexes [Fe 2 {μ-η 1 :η 3 -C(NMe 2 )CH=CR}(μ-CO)(CO)(Cp) 2 ][SO 3 CF 3 ] undergo nucleophilic addition at the iminium C or at α-C position, which is uncommon since non-coordinated vinyliminium species generally undergo conjugated (Michael type) nucleophilic attack. Likewise, bridging vinyliminium ligands undergo new and unusual transformations consisting of the deprotonation and replacement of the α-CH by a variety of functional groups. These reactions, resulting in the formation of C–C and C–heteroatom single and double bonds, produce new bridging ligands of the type [μ-C(NMe 2 )C(X)CR) (X = S, O, Se, SPh, CNMe, NNCHCO 2 Me]. Removal of the vinylalkylidene ligands from the bridging coordination is achieved by a [3 + 2] cycloaddition with alkynes. The reaction leads to the formation of ferrocenes containing one polysubstituted Cp ring, which results from the cycloaddition of the bridging C 3 ligand with alkynes. This result suggests a new possible route for the synthesis of polyfunctionalized ferrocenes.