Volume 78, Issue 2

The past 25 years have witnessed some quite extraordinary advances in the development and synthetic application of organometallic reagents and catalysts. This is reflected in the history of the conference series Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS), which has established itself as a popular and enduring international forum for presentation and discussion of mainstream developments and opportunities in this field. The series was inaugurated in Fort Collins, Colorado, USA in 1981. Proceedings of the plenary program of that event were published in Pure and Applied Chemistry (PAC) 53 (12), 1981, and the topic has since become a regular feature in the Journal, with the distinction of having recorded some of the seminal advances of the period. Indeed, as the OMCOS series has grown in support and stature over the years, it has played a leading role in a trend toward more in-depth coverage of the scientific proceedings of selected IUPAC-sponsored conferences. There is encouraging evidence that this practice has the benefit of extending publication opportunities to the rising younger generation of scientists, thereby broadening and enriching the more traditional coverage of plenary proceedings, and adding value to the published record. It is perhaps unsurprising that OMCOS has emerged as one of the leading series in the calendar of regular, IUPAC-sponsored conferences. How do we know that? Obviously, the committed participation of a succession of enthusiastic organizers and contributors, and consistently high attendance figures over the years, support this contention. More convincingly, the series generates what is regularly the most highly cited feature of PAC . For example, data collected on 30 April 2005 reveal that the OMCOS-9 collection with 239 citations averaging 14.9 citations per paper, and the OMCOS-10 collection with 408 citations averaging 21.5 citations per paper, head the citation rates for the Journal in those years. Early indications are that OMCOS-11 and OMCOS-12 head the comparable ratings of regular features for 2002 and 2004, respectively, although these more recent data are obviously in flux and still provisional. Publication policy is responsive to these indicators of successful conference series, in the confident expectation that they will continue to serve the Journal readership with topical and sought-after content. These expectations have been handsomely fulfilled by OMCOS-13, held in Geneva, Switzerland on 17-21 July 2005, and this Special Topic issue is devoted to exclusive coverage of the event. No less than 37 papers drawn from invitations to all invited presenters on the main lecture program and a selection of meritorious contributed works feature, and constitute a salute to the centrality of this theme in modern organic synthesis. It is also a tribute to the exceptional efforts of the organizers and authors, whose energy and cooperation have ensured an expeditious passage to publication of this representative record of an outstanding event. James R. Bull Scientific Editor

The 13th IUPAC International Symposium on Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS-13<http://omcos13.unige.ch/>) was held in Geneva, Switzerland, from 17-21 July 2005. The aim of this series of symposia is to bring together chemists from academia and industry to define and discuss the most recent developments in the areas of catalysis, new organometallic reagents and reactions, and new materials chemistry. In 2001, Sharpless, Noyori, and Knowles received the Nobel Prize for their work in this area of chemistry; and the high profile has been maintained by the award of the 2005 Nobel Prize in Chemistry to Chauvin, Grubbs, and Schrock for the development of the metathesis method in organic synthesis. OMCOS-13 had a record number of nearly 1200 participants from 41 countries, and there was an encouragingly high proportion of young scientists in attendance. Very strong Asian participation at this conference reflected the outstanding level of research and leadership in this field from countries such as Japan, China, South Korea, and Taiwan. Prof. Shengming Ma, from the Shanghai Institute of Organic Chemistry of the Chinese Academy of Science and the Department of Chemistry, Zhejiang University, China received the OMCOS-13 Award (sponsored by the Yen Chuang Foundation and Springer Verlag). The prize was awarded for his creative research contributions in the field of transition-metal-catalyzed reactions of allenes. Apart from the OMCOS-13 Award lecture, there were 23 plenary lectures and 20 oral communications that dealt with aspects of reactivity and chemoselectivity of main group and transition-metal organometallics. Stereoselectivity issues also figured prominently with a particular emphasis on asymmetric synthesis and catalysis. Mechanistic insights, new reagents for synthesis, new catalyst and ligand design, and ligand effects were other important topics. The quality of the 620 posters that were on display during the entire conference was also outstanding. This extraordinary poster session was highlighted with the Monday evening "poster party" and culminated in the awarding of 37 poster prizes. OMCOS-13 was held as a single session conference in an impressive lecture theater and a large exhibition area in the center of Geneva at a superb lakefront location. It was a fitting venue for the firstclass science that was presented. Thirty-seven lecturers of OMCOS-13 present their chemistry in this issue of Pure and Applied Chemistry and provide a fine recollection of last summer's conference. The 14th edition of OMCOS will be held in Nara, Japan (2-6 August 2007) under the chairmanship of Prof. Koichiro Oshima. Alexandre Alexakis OMCOS-13 Co-chair E. Peter Kündig OMCOS-13 Co-chair

Pathways for carbometallation of simple allenes and allenes bearing a nucleophilic functionality with RMX have been discussed. The bisallene approaches for the efficient synthesis of carbocycles and heterocycles have been developed.

Studies on the use of easily accessible heteroatom-substituted secondary phosphine oxides as preligands for cross-coupling reactions are described. These air-stable sterically hindered phosphine oxides allow for efficient palladium-catalyzed Suzuki- and nickel-catalyzed Kumada-coupling reactions using electronically deactivated aryl chlorides. In addition, they enable nickel-catalyzed coupling reactions of magnesium organyls with aryl fluorides at ambient temperature, and ruthenium-catalyzed coupling reactions of aryl chlorides via C-H bond activation. Finally, the application of modular diamino phosphine chlorides as preligands for a variety of transition-metal-catalyzed C-C and C-N bond formation reactions employing electron-rich aryl chlorides is presented.

The anionotropic 1,2-migration of an organic substituent from a tetrasubstituted borate ion, often referred to as an "ate" complex, to an acceptor atom is at the basis of the most useful application of organoboranes in organic synthesis. We recently showed that chiral sulfur ylides react with boranes to give homologated products with high enantiomeric excess. In considering reactions with mixed boranes, the issue of which group would migrate arises. Although we are primarily interested in sulfur ylide reactions with boranes, in this review we have summarized the most important factors that are responsible for which group migrates from a broad spectrum of reactions involving borate complexes. We also discuss the use of blocking/nonmigrating groups and highlight when they are effective and not effective. Consideration of the most important factors that affect the outcome of which group migrates and understanding how and why blocking groups work, provides a strategy for designing boranes with nonmigrating groups for use in new reactions of these useful synthetic intermediates.

In recent years, new processes based on transition-metal-mediated intramolecular addition reaction of heteronucleophiles and stabilized carbon nucleophiles to unactivated alkenes and alkynes have been developed in our laboratory. In this article, we summarize a number of recent synthetic applications of these new processes. Emphasis is placed on the development of multicomponent reactions based on a Pd-mediated intramolecular cyclization coupled with a carbon-carbon bond-forming reaction. Applications of this methodology to the synthesis of natural lignans are also reported.

The photochemical liberation of functional groups is an attractive alternative to the traditional chemical approach. Several photolabile protecting groups have been developed in the past decades, but they were mainly designed to protect amines and carboxylic acids. In this account, we present some of our recent work on the photochemical release of other functions, such as silanols, aldehydes, and ketones. We also describe a new form of differentiation among several photolabile groups by the use of monochromatic light tuned to each of them: the chromatic orthogonality.

A new concept for generation of chelating ligand libraries for homogeneous metal complex catalysis based on self-assembly is presented. Thus, self-assembly of structurally simple monodentate ligands in order to give structurally more complex bidentate ligands is achieved employing hydrogen bonding. Based on this concept and on the 2-pyridone/hydroxypyridine tautomeric system, a new rhodium catalyst was identified which operated with excellent activity and regioselectivity upon hydroformylation of terminal alkenes. In order to generate defined unsymmetrical heterodimeric ligands, an A-T base pair analog-the aminopyridine/isoquinolone system-was developed which allows for complementary hydrogen bonding. Based on this platform, a 4 x 4 phosphine ligand library was screened in the course of the rhodium-catalyzed hydroformylation of 1-octene. A catalyst operating with outstanding activity and regioselectivity in favor of the linear aldehyde was discovered.

Structurally well-defined transition-metal complexes of 1-phosphino-2-sulfenylferrocene (Fesulphos ligands) act as highly efficient catalysts in a variety of mechanistically different transformations. Excellent enantioselectivities were achieved in Pd-catalyzed allylic substitutions, desymmetrization of meso -heterobicyclic alkenes by Pd-catalyzed addition of dialkylzinc reagents, Pd-catalyzed Diels-Alder reaction of cyclopentadiene with N -acryloyl oxazolidinones, and in Cu-catalyzed formal aza-Diels-Alder reaction of Danishefsky diene to N -sulfonyl aldimines.

Optically active tertiary aminonaphthol ligands were obtained by a new, convenient procedure and were found to catalyze the enantioselective alkenyl and phenyl transfer to aldehydes in high yields and excellent enantiomeric excesses (ee's). The catalytic asymmetric introduction of alkynyl functionality to α-amino acid derivatives was realized by the direct addition of terminal alkynes to α-imino ester in the presence of chiral copper(I) complex under mild reaction conditions.

Two GaCl 3 -catalyzed reactions, which utilize isocyanides as a one-carbon unit, are described: a [4+1] cycloaddition of α,β-unsaturated carbonyl compounds with isocyanides, and an insertion reaction of isocyanides into a C-O bond of ketals and acetals. The relatively low affinity of GaCl 3 toward heteroatoms enables the successful catalysis.

The treatment of activated alkynes with catalytic amounts of Stryker's reagent and tributylstannane resulted in hydrostannation. The reaction proceeds with high regioselectivity to produce α-stannated vinylstannanes exclusively.

The Reformatsky reaction is the well-recognized carbon-carbon bond-forming reaction of α-halo esters with aldehydes or ketones in the presence of Zn metal to give β-hydroxy esters. Recently, it has been reported that Rh- and Ni-catalyzed Reformatsky reaction, in which R 2 Zn (R = Me, Et) acts as the Zn source, reacted smoothly with carbonyl compounds and imines. Taking advantage of N -methylephedrine as a cheap and recoverable chiral ligand, we have discovered the first homogeneous enantioselective Ni-catalyzed imino Reformatsky reaction. The process is a one-pot, three-component reaction, in which Me 2 Zn plays multiple roles as dehydrating agent, reductant, and coordinating metal. Broad scope, high enantiomeric excess, and a simple procedure are adding value to our findings.

Two strategies for the development of practical asymmetric catalysis have been discussed in this article. The first part of this article focuses on the design and screening of highly efficient and enantioselective chiral catalysts for asymmetric hydrogenation reactions employing combinatorial approach. The second part presents a conceptually new strategy (i.e., "self-supporting" approach) for the immobilization of homogeneous catalysts through assembly of chiral multitopic ligands and metal ions without using any support. The success of this strategy will be exemplified in heterogeneous asymmetric carbonyl-ene, sulfoxidation, and epoxidation, as well as in asymmetric hydrogenation reactions.

Nineteen chiral tropos phosphorus ligands, based on a flexible (tropos) biphenol unit and a chiral P-bound alcohol (11 phosphites) or secondary amine (8 phosphoramidites), were screened, individually and as a combination of two, in various Rh-catalyzed asymmetric reactions. In the Rh-catalyzed asymmetric conjugate addition of phenylboronic acid to cyclic enones, enantiomeric excesses (ee's) up to 95 % were obtained with a 1:1 mixture of a phosphite [derived from (1 R ,2 S )-2-(1-methyl-1-phenylethyl)cyclohexanol] and a phosphoramidite [derived from ( S , S )-2,5-diphenylpyrrolidine]. In the mixed Rh precatalyst, which was characterized via 31 P-NMR, the biphenol-derived phosphite is free to rotate (tropos) while the biphenol-derived phosphoramidite shows a temperature-dependent tropos/atropos behavior (coalescence temperature = 310 K). The ligands were also screened in the hydrogenation of dehydro-α-amino acids and dehydro-β-amino acids. Ee's up to 98% were obtained for the dehydro-α-amino acids, using the combination of a phosphite [derived from (1 R ,2 S )-2-phenyl-1-cyclohexanol] and a phosphoramidite [derived from ( S , S )-bis(α-methylbenzyl)amine]. The reaction was optimized by lowering the phosphite/phosphoramidite ratio to 0.25:1.75 with a resulting improvement of the product ee.

The synthesis of new tridentate, isoquinoline-derived ligands, involving successive Suzuki cross-coupling reactions, is described. We were able to resolve 1-[3-(2-hydroxy-phenyl)-isoquinolin-1-yl]-naphthalen-2-ol via molecular complexation with N -benzylcinchonidinium chloride, whereas 1,3-bis(2-hydroxy-naphthalen-1-yl)-isoquinoline was resolved by chromatographic separation of its epimeric camphorsulfonates. Their barrier to rotation about the central biaryl axis was evaluated via racemization studies. Application of enantiopure 1,3-bis(2-hydroxynaphthalen-1-yl)-isoquinoline in the addition of diethylzinc to aldehydes proceeded in moderate yield but without asymmetric induction. A new tridentate ligand, 4- tert -butyl-2-chloro-6-[1-(2-hydroxymethyl-naphthalen-1-yl)-isoquinolin-3-yl]-phenol, was prepared in good yield and resolved by semipreparative high-performance liquid chromatography (HPLC). Its application in the addition of diethylzinc to a range of aromatic aldehydes proceeded in near perfect enantioselectivities at low ligand loadings of 1 mol %.

An overview of the role of 3-aminopyrrolidine lithium amides (3-APLi's) as chiral ligands for alkyllithiums (AlkLi's) is presented. Synthetic developments as well as NMR characterizations and computational interpretations have been simultaneously and complementarily conducted to improve the ligand design for a model reaction that is the condensation of AlkLi's on o -tolualdehyde, for which enantiomeric excesses up to 80 % were obtained. This study describes the whole chain going from the synthesis of the chiral 3-aminopyrrolidines (3-APs) (18 different 3-APs synthesized) to the characterization of the noncovalent mixed aggregates resulting from the interaction between the organolithium partners (3-APLi:AlkLi). Finally, the docking of the aldehyde on one lithium of the aggregate was analyzed by theoretical means on simplified models, in an attempt to understand the structure of the fully loaded pretransition complexes.

An efficient synthesis of α-aminoallenylstannane from propargyloxazolidinone has been developed. It undergoes reaction with aldehydes to give homopropargylic alcohols with high syn selectivity. Epoxides undergo a similar reaction preceded by rearrangement to the aldehyde. These alcohols were used in the synthesis of β-amino acids, azasugars, and deoxyaminohexoses. Imines underwent reaction with this stannane to give 1,2-diamines. The related propargylborane reacts with aldehydes to produce allenyl carbinols. The Co 2 (CO) 6 complexes of propargyloxazolidinones were developed as an α-aminopropargyl cation equivalent.

Our development of dicationic palladium(II) complexes for asymmetric hydroamination reactions, particularly the aza-Michael addition, is reviewed.

Several Pd-catalyzed cyclization methods were developed, including norbornene-mediated Catellani-type reactions, a Pd-catalyzed coupling reaction of aryl iodides and allyl moieties, and a tandem C-N/C-C coupling of gem -dihalovinyl systems. These ring-forming methods were applied to the synthesis of highly functionalized carbocyclic and heterocyclic compounds. Intermolecular Pd-catalyzed methods for synthesis of highly substituted arene compounds were also developed.

Studies regarding the transition-metal-catalyzed decomposition of nitrogen derivatives toward Curtius rearrangement and the formation of nitrenes which undergo C-H insertion and aziridination reactions are presented. These processes lead to the formation of C-N bond with a high level of selectivity and efficiency.

Formation of C-C, C-N, and C-H bonds using three heterogeneous catalysts in the form of nickel-in-charcoal (Ni/C), nickel-on-graphite (Ni/C g ), and copper-in-charcoal (Cu/C) are described.

A highly efficient approach to the synthesis of spiroketals involves the double cyclization of alkynyl diols using transition-metal catalysts. The iridium complex [Ir(PyP)(CO) 2 ]BPh 4 where PyP = 1-[(2-diphenylphosphino)ethyl]pyrazole is an effective catalyst for promoting the formation of spiroketals via this double hydroalkoxylation reaction. The complex promotes the formation of a series of spiroketal products from alkynyl diol starting materials such as 3-ethynylpentane-1,5-diol and 2-(4-hydroxybut-1-ynyl)benzyl alcohol. Stereoselective cyclization occurs for 3-ethynylpentane-1,5-diol, 3-ethynylhexane-1,6-diol. The cycloadditions occur in all but one case with quantitative conversion in under 24 h at 120 °C.

The asymmetric hydroxylation and fluorination catalyst [Ru(OEt 2 ) 2 (PNNP)] 2+ (PNNP = chiral tetradentate ligand with a P 2 N 2 donor set) reacts with 1,3-dicarbonyl compounds to give dicationic adducts and, upon deprotonation, the corresponding enolato complexes. The relevance of these species to catalytic O- and F-transfer is investigated.

The development of a novel reaction ideal in terms of atom economy was achieved. The scope of the reaction was evaluated in the presence of Pd and Pt catalysts. The first enantioselective Pt-promoted enyne carboalkoxycyclization was developed in up to 85 % stereoselectivity. This ideal atom-economical reaction afforded the corresponding functionalized five-membered carbo- and heterocycles in good to excellent yields. The use of silver salts combined with ( R )-Ph-BINEPINE, a monophosphane atropisomeric ligand, was found to be the best-suited combination for moderate to high enantioselectivities on carbonated and nitrogenated substrates.

Reaction of benzaldehyde with ethyl cyanoformate in the presence of Lewis acidic Ti(IV) complexes of bispyridylamide or salen ligands and Lewis basic amines affords the O -alkoxycarbonylated cyanohydrin. In the presence of the salen-based catalytic system, acetyl cyanide can also be added to benzaldehyde, providing a highly enantioselective direct route to the O -acetylated cyanohydrin.

The silyl substituent of 3-silylcyclobutene prefers inward rotation rather than outward rotation during a thermal ring-opening reaction, giving the Z -isomer predominantly. This intriguing behavior was explained by assuming electron-accepting interactions between the low-lying σ*-orbital of the silicon-carbon linkage and the highest occupied molecular orbital (HOMO) of the opening cyclobutene system, which are possible only in the inward transition state. On the basis of this finding, a novel method for the stereoselective synthesis of functionalized 1,3-butadiene derivatives from cyclobutenones was developed. Boryl substituents exhibit even stronger preference for inward rotation than silyl substituents as a result of electron delocalization from the cyclobutene HOMO into the vacant p-orbital of boron at the inward transition state.

This account deals with an overview of the development of catalytic addition reactions of carbonyl compounds to alkynes catalyzed by a variety of indium salts. The new C-C bond formation reactions provide a powerful tool for α-functionalization of carbonyl compounds, including direct α-vinylation with acetylene, regioselective α-alkenylation, and α-ynenylation that can be applied to a modular synthesis of α-arylated β-keto esters.

Readily accessible and highly stable alkenyl- and aryl[2-(hydroxymethyl)phenyl]dimethylsilanes cross-couple with various aryl and alkenyl halides under mild reaction conditions employing K 2 CO 3 as a base at 35-80 °C. The reaction tolerates a diverse range of functional groups including silyl protections. The silicon residue, cyclic silyl ether, is readily recovered and reused on a gram-scale synthesis. Intramolecular coordination of a proximal hydroxyl group is considered to efficiently form pentacoordinated silicates having a transferable group at an axial position.

Without suffering from β-elimination, cobalt complexes allow cross-coupling reactions of alkyl halides with Grignard reagents. A combination of a cobalt complex and trimethylsilylmethyl Grignard reagent effects Mizoroki-Heck-type reaction of alkyl halide with styrene, which conventional palladium catalysts have never made possible. Cobalt exhibits intriguing catalytic activities on hydrophosphination and allylzincation of alkynes. Silylmethylcobalt reagent is a powerful tool for the synthesis of highly silylated ethenes.

The synthesis of ortho -(trimethylsilyl)vinyl triflates is described. Fluoride-induced decomposition of these triflates leads to the generation of strained cycloallenes and cycloalkynes under mild reaction conditions. The generation rate of these highly reactive intermediates can be modulated by modifying the solubility of the fluoride source. The slow generation of cyclic allenes and alkynes is a prerequisite for their use in homogeneous catalysis.

Cycloruthenated complexes obtained by direct C-H activation of enantiopure aromatic primary and secondary amines are efficient catalysts in asymmetric hydride transfer reaction. Reduction of acetophenone has been achieved rapidly with enantiomeric excesses (ee's) ranging from 38 to 89 %. The importance of Ru-C bond in the catalytic efficiency is highlighted.

An unprecedented catalytic asymmetric ring-opening of easily accessible 2,3-heterosubstituted norbornenes with hard alkyl metals (R-M), is able to give a practical regio- and stereoselective access to hetero-functionalized alkyl cyclopentenes in an enantioenriched form. The copper-catalyzed desymmetrization reaction with trialkylaluminums of sterically hindered and rigid, tri- or tetracyclic Diels-Alder adducts, easily available by cycloaddition reaction of cyclopentadiene with 4-phenyl-urazole and 2,3-phthalazine-1,4-dione, proved to be particularly efficient. Interestingly, the chirality of the amine part of the BINOL-based phosphoramidite is able to impose the absolute stereochemistry of the corresponding adducts.

Tandem sequences consisting of an olefin metathesis step and a subsequent non-metathesis reaction become accessible by organometallic transformations of the Ru-carbene species in situ. This contribution highlights some tandem sequences that rely on the conversion of the metathesis catalyst to Ru-hydrides, with special emphasis on the tandem ring-closing metathesis (RCM)-double-bond isomerization sequence.

Chiral Pd aqua and µ-hydroxo complexes were found to act as mild Brønsted acids and bases, and chiral Pd enolates were generated from these complexes even under acidic conditions. Highly enantioselective Michael addition, Mannich-type reaction, fluorination, and conjugate addition of amines have been developed based on the acid-base character of these Pd complexes.

Asymmetric synthesis of helicenes and their congeners has been demonstrated to rely either on enantioselective Ni 0 /PR 3 * -catalyzed [2+2+2] cycloisomerization of triynes or on diastereoselective Co I -catalyzed [2+2+2] cycloisomerization of chiral triynes. The former approach providing tetrahydrohelicenes in a nonracemic form requires further development as moderate enantioselectivities (up to 54 % ee) have so far been achieved under kinetic control. The latter approach affording helicene-like structures in a diastereomerically enriched form allows for reaching good to excellent diastereoselectivities (up to 100:0) under thermodynamic control.

The chirality-directed self-assembly of bifunctional subunits around a structural metal - typically, zinc(II) - is used to form a heteroleptic complex in which a second set of ligating groups are suitably disposed to bind a second metal, forming a heterobimetallic catalyst system. We find that subtle changes in the structural backbone (i.e., ligand scaffold) of such chiral bidentate self-assembled ligands (SALs) can be used to manipulate the ligand topography and chiral environment around catalytic metal; thus, the scaffold can be optimized to maximize asymmetric induction. Using this combinatorial strategy for ligand synthesis, a preliminary study was carried out in which a library of 110 SALs was evaluated in the rhodium-catalyzed asymmetric hydrogenation of a simple N -acyl enamide. The level of enantioselectivity obtained varies from near racemic to greater than 80 % ee as a function of the ligand scaffold, with the possibility of further improvement yet to be explored.

Highly stereoselective 1,2-additions of AlMe 3 or its air-stable analog DABCO(AlMe 3 ) 2 to aldehydes are realized in the presence of a Ni(acac) 2 -derived catalyst using phosphoramidite ligands giving sec -alcohols in up to 95 % ee. Very high turnover number (TON) (>1500) and turnover frequency (TOF) (>350 h -1 ) values can be realized in these reactions. The substrate range, trials of various (DABCO) a (AlR 3 ) b reagents ( a = 0.1; b = 1.2; R = Me, Et, Bu i ), ligands, and molecular modeling studies are used to propose a working model for the catalytic cycle and the origin of the stereoselectivity. The phosphoramidite ligand is proposed to bind the nickel in an η 2 manner via the P -donor and one of the C=C aryl bonds of the CHAr amine group. Preliminary studies indicate that DABCO(AlMe 3 ) 2 can also be used as a methyl source in Pd-catalyzed cross-coupling reactions of ArX (X = Br, I) species.

A catalytic asymmetric protonation of trimethylsilyl enolates was achieved using a 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP)-silver(I) fluoride complex as a chiral catalyst in a mixed solvent consisting of dichloromethane and methanol. Various nonracemic ketones possessing a tertiary asymmetric carbon at the α-position were prepared with high enantioselectivity up to 99 % ee.