Volume 76, Issue 3

Electrophilic transition-metal complexes catalyze the reaction of enynes in the presence of water or alcohols to give hydroxy- or alkoxycyclization derivatives. The reaction proceeds by the anti addition of the alkene and the metal to the alkyne. The key intermediates in this reaction are cyclopropyl metal carbenes, which are also probably involved in the metathesis-type rearrangement of enynes. A general scheme is proposed for the cyclization of enynes initiated by the coordination of the metal to the enyne by transition metals, which included 5- exo -dig and 6- endo -dig pathways. The intramolecular reaction of furans with alkynes also proceeds via cyclopropyl metal carbenes.

Asymmetric 1,4-arylation and -alkenylation was achieved by use of organoboronic acids or their derivatives in the presence of a rhodium catalyst coordinated with binap or its related ligands. The scope of this asymmetric addition is very broad, α, β-unsaturated ketones, esters, amides, 1-alkenylphosphonates, and 1-nitroalkenes being efficiently converted into the corresponding 1,4-addition products with over 95% enantioselectivity. The catalytic cycle in water is proposed to involve three intermediates [aryl-or alkenyl-rhodium (oxa-π-allyl) rhodium, and hydroxo-rhodium] by NMR studies on the rhodium intermediates.

The synthesis of planar chiral η 3 -allylmolybdenum complexes is described together with some examples of the nucleophilic addition of organocopper(I) reagents.

Synthesis routes are described, allowing all known jasmonoids as well as their enantiomers to be synthesized in enantiomerically and diastereomerically pure form. The routes are based on a set of closely related lactones containing an electrophilic allylic moiety, which are accessible via asymmetric Pd-catalyzed allylic alkylation. Regio- and diastereoselective S N 2'- anti -reactions of the electrophilic lactones with organocopper compounds furnished 2,3- cis -disubstituted cyclopentenones, which were further transformed into the target compounds, i.e., 12-oxophytodienoic acid (12-OPDA) in excellent overall yields. The methodology also allowed iridoids and isoprostanes to be prepared. The configuration of an Archaea membrane lipid constituent containing cyclopentane rings was determined by total synthesis of a diol that was also obtained by degradation of the natural product.

Studies on the development of palladium, nickel, and rhodium catalysts for the hydroamination of dienes and vinylarenes are described. Enantioselective catalysts based on palladium have been developed for the addition of arylamines to dienes and for Markovnikov addition of arylamines to vinylarenes. In addition, nickel catalysts for the addition of aliphatic amines to dienes have been developed, and rhodium catalysts for the first transition metal-catalyzed aminations of vinylarenes that generate terminal amines as the major product are described. Mechanistic data on the hydroamination of vinylarenes with palladium and rhodium is also provided.

In the first part of the lecture, we will discuss the one-pot preparation of chiral homoallylic alcohol and amine derivatives by a copper-catalyzed four-component reaction. In this process, three new carbon-carbon bonds as well as a quaternary and a tertiary chiral center are created with excellent regio- and diastereoselectivities. When the reaction was performed without adding external electrophiles, a β-elimination reaction took place to give polysubstituted allenes in good overall yields. This strategy of zinc-homologation followed by a β-elimination reaction was also synthetically used for the transformation of sp 3 sulfoxides into olefins with potential application in asymmetric synthesis. Finally, in the second part of this lecture, the stereoselective preparation of metallated dienes in only two chemical steps from commercially available products will be described. This new strategy is based on a tandem allylic C-H bond activation of a remote ω-double bond followed by an elimination reaction.

Asymmetric activation of aquo Pd catalysts with tropos biphenylphosphine (BIPHEP) ligands by a chiral diaminobinaphtyl (DABN) activator exhibits a remarkable negative nonlinear effect, (–)-NLE, with higher catalytic efficiency than that achieved by enantiopure atropos BINAP- or tropos BIPHEP-Pd catalysts without DABN activator.

Two examples are presented for the synthesis of optically active polymers with main-chain chirality from achiral monomers using chiral metal-complexes as catalysts. Asymmetric alternating copolymerization of α-olefins with carbon monoxide provided optically active polyketones when catalyzed by an ( R,S )-BINAPHOS-Pd complex. From propene and CO, highly isotactic polyketone with high enantioselectivity (>97 % like diad and >95 % ee). Spectroscopic and theoretical studies revealed that the olefin insertion is the key step for the enantiofacial selection and that this step takes place at cis to the phosphine part of ( R,S )-BINAPHOS. The catalyst is applicable not only to propene/CO but also to styrene/CO, which enabled the first asymmetric terpolymerization of propene/styrene/CO. The catalyst tolerates funational groups such as fluorocarbons and a nitrile group so that they can be incorporated in the side chain. Optically active polycarbonate was also synthesized by the alternating copolymerization of cyclohexene oxide with carbon dioxide via the desymmetrization of the meso -epoxide. Dinuclei zinc species prepared from diethylzinc, ethanol, and α,α'-diphenylprolinol, was revealed to be the real active species.

This article summarizes our recent achievements in the asymmetric catalytic formation of chiral alcohols using 3-substituted, 2-azanorbornyl-based ligands. The use of this structural unit in ligand synthesis offers several advantages over the analogous proline chemistry, such as equal availability of both enantiomers and increased rigidity of the catalysts. This ligand has been found to be very useful for the two reactions described in this paper: the ruthenium-catalyzed transfer hydrogenation of ketones, and the base-mediated rearrangement of epoxides.

The stereochemistry of epoxide carbonylation using bimetallic [Lewis acid] + [Co(CO) 4 ] - complexes is reported. The achiral complex [(salph)Al(THF) 2 ][Co(CO) 4 ] stereospecifically carbonylates cis - and trans -2-butene oxide to the trans - and cis -β-lactones, respectively. Preliminary experiments regarding the carbonylative kinetic resolution of racemic trans -2-butene oxide using the enantiomerically pure complex [( R,R -salcy)Al(THF) 2 ][Co(CO) 4 ] are also reported.

In palladium-catalyzed Heck, Stille, or Sonogashira reactions, the nucleophiles-respectively, alkenes, vinylstannanes, or alkynes-are involved in carbopalladation or transmetallation steps that follow the oxidative addition of an aryl halide or triflate to a Pd 0 complex. As soon as the nucleophiles possess a C=C or a C 'triple-bond' C bond capable of coordinating the Pd 0 complex active in the oxidative addition, they play a dual role since they interfere in the oxidative addition by a decelerating effect due to a partial coordination of the active Pd 0 complex. Indeed, its concentration decreases due to the formation of either unreactive complexes (η 2 -RCH=CH 2 )Pd 0 L 2 (R = Ph, CO 2 Et, L = PPh 3 ; R = Bu 3 Sn, L = AsPh 3 ), (η 2 -RCH=CH 2 )Pd 0 L 2 (OAc) - (R = Ph, L = PPh 3 ), (η 2 -R-C 'triple-bond' CH)Pd 0 L 2 (R = Ph, L = PPh 3 ) or more slowly reactive complexes (η 2 -R-C 'triple-bond' CH)Pd 0 L 2 (R = CO 2 Et, L = PPh 3 ), (η 2 -RCH=CH 2 )Pd 0 L 2 (R= CO 2 Me, L 2 = dppf). Whenever the oxidative addition is faster than the ensuing carbopalladation or transmetallation, the decelerating effect of the nucleophiles in the oxidative addition is in favor of a better efficiency for the catalytic cycle by bringing the rate of the fast oxidative addition closer to that of the slow carbopalladation or transmetallation steps.

Herein we describe the chelation-assisted C-H and C-C bond activation by Rh(I) catalysts and its application directed toward the formation of C-C bonds in organic synthesis.

Reaction of the C 2 -symmetric "Trost modular ligand" with cationic Pd(II) allyl fragments allows isolation of air- and bench-stable pro-catalysts for the asymmetric allylic alkylation of racemic cycloalkenyl esters. In solution, three distinct complexation modes are observed. When mixed in a ligand/Pd ratio of 1/2, a binuclear bis- P,O -chelate complex is generated. This species does not induce enantioselectivity in the reaction. In contrast, with a ligand/Pd ratio of 1/1, a highly enantioselective, P,P -coordinated pro-catalyst system is generated in which there are two basic coordination modes: monomeric and oligomeric. The monomeric form is mononuclear and exists as two 13-membered chelates, isomeric through loss of C 2 -symmetry in the ligand. The oligomeric form is polynuclear and forms chains and rings of alternating ligand and cationic Pd(allyl) units, one of which was identified by single-crystal X-ray diffraction. In solution, the monomeric and oligomeric species are in dynamic equilibrium with populations and interconversion rates controlled by concentration, temperature, and counterion. Isotopic desymmetrization analysis suggests that the monomer-oligomer equilibrium plays a crucial role in both the selectivity and efficiency of the asymmetric allylic alkylation reaction.

Due to frequent occurrence of nitrogen-containing groups among the biologically active compounds, chemoselective functionalization of organic molecules with nitrogen-containing functional groups is an important area of organic synthesis. We have proposed and implemented a new strategy toward design of nitrogen-transfer reactions on inert electrode surfaces with a particular focus on the generation and trapping of highly reactive nitrogen-transfer agents. A wide range of structurally dissimilar olefins can be readily transformed into the corresponding aziridines. The resulting aziridines are precursors to a range of catalysts via nucleophilic ring-opening with diaryl- and dialkyl phosphines. Another strategy explored in the context of oxidative nitrogen transfer is cycloamination of olefins using NH aziridines.

The perfluoroaryl borane B(C 6 F 5 ) 3 is an effective catalyst for a variety of organic transformations. In the hydrosilation of carbonyl functions, it activates the silane rather than the carbonyl substrate. In allylstannation reactions, two competing reaction pathways are observed, one involving tin cation catalysis, the other "true" borane catalysis. For B(C 6 F 5 ) 3 , the former mechanism dominates, while for the weaker Lewis acid PhB(C 6 F 5 ) 2 , the latter pathway is more prominent. Thus, chiral boranes of similar Lewis acid strength to PhB(C 6 F 5 ) 2 have the potential to mediate asymmetric allylstannation of aldehyde substrates.

The major features of the catalytic cycle, including structures of key intermediates, have been determined for the molybdenum-catalyzed asymmetric alkylation. The crystal structure of the π-allyl intermediate exhibits 3-point binding of an anionic ligand. Based on NMR analysis, this species adopts in solution a structure consistent with that observed in the solid state. For the allylic alkylation, the crystal structure predicts the opposite stereochemistry vs. that observed experimentally, which suggests that either the reaction proceeds via a minor isomer (Curtin-Hammett conditions) or with retention of configuration. In addition, CO transfer, promoted by Mo(CO) 6 , has been found to play a key role in catalyst turnover.

Homogeneous organometallic catalysts have a great potential for the development of sustainable synthetic processes. There is, however, an urgent need for the development of new techniques to separate products and catalysts efficiently, allowing for recycling and reuse of the precious catalyst. The unique solvent properties of supercritical carbon dioxide offer new approaches for the immobilization of organometallic catalysts, many of which are suitable for efficient continuous-flow operation. Recent research in this field tries to combine the molecular nature of organometallic catalysts with the reaction-engineering aspect of multiphase catalysis.

The cyclopropanation of various alkenes with different diazoester compounds was investigated using two different μ-oxo-bis[(salen)iron(III)] complexes, [Fe(3,3',5,5'- t Bu 4 salen)] 2 O and [Fe(salen)] 2 O. Ethyl diazoacetate (EDA), tert -butyl diazoacetate ( t BDA), and ethyl diazoacetoacetate (EDAA) were used with mono- and disubstituted terminal olefins (styrene and 1,1-diphenyl ethylene, respectively), internal olefin ( trans -β-methyl styrene), and an electron-rich alkene ( n -butyl vinyl ether). Moderate-to-good cyclopropanation yields were obtained for most substrates.

The cyclization reactions of 2,3-allenoic acids or their salts with optically active bases affording butenolides are discussed. Two reaction pathways were observed: (1) intermolecular carbometallation-intramolecular allylation; (2) cyclic oxymetallation-reductive elimination. High efficiency of chirality transfer was realized with the latter case.

3-halopropenyl esters, readily prepared by the addition of acyl halides to acrolein, react with zinc, indium, and chromium(II), thus opening a route to a new class of oxygen-substituted allylic organometallic compounds. Indium and zinc reagents smoothly add to carbonyl compounds, affording alk-1-en-3,4-diol derivatives in a variety of synthetic procedures which include typical Grignard stepwise conditions as well as Barbier one-pot protocols. Using zinc and indium in water or aprotic solvents, simple diastereoselectivity was found to depend on the nature of the carbonyl compound; conjugated aldehydes favor formation of syn-adducts while unconjugated aldehydes favor anti -adducts. Moving to chromium, a reversal of regioselectivity was observed in favor of (Z)-4-hydroxy-enolacetates, flexible protected forms of homoaldols. Chromium complexes are generated in a catalytic cycle based on the combined use of the redox Mn(0)/Cr(III) couple and of TMSCl. When the Cr-catalyzed reaction is carried out in the presence of Jacobsen's Salen ligand, the regiochemical outcome of the reaction is again reversed, and syn -alk-1-en-3,4-diols are formed in high ee's.

The reaction of a 3-butenyl β-diketone with a catalytic amount of PdCl 2 (CH 3 CN) 2 in dioxane at room temperature led to olefin hydroalkylation and formation of the corresponding 2-acylcyclohexanone in good yield as a single regioisomer. Deuterium-labeling experiments for the hydroalkylation of 7-octene-2,4-dione were in accord with a mechanism involving outer-sphere attack of the pendant enol on a palladium-complexed olefin to form a palladium cyclohexyl species, followed by palladium migration via iterative β-hydride elimination/addition and protonolysis from a palladium enolate complex. In comparison to a 3-butenyl β-diketone, reaction of a 4-pentenyl β-diketone with a catalytic amount of PdCl 2 (CH 3 CN) 2 in the presence of CuCl 2 led to oxidative alkylation and formation of the corresponding 2-acyl-3-methyl-2-cyclohexenone in good yield as a single isomer. Unactivated olefins tethered to less reactive carbon nucleophiles such as β-keto esters, α-aryl ketones, and even dialkyl ketones underwent palladium-catalyzed hydroalkylation in the presence of Me 3 SiCl or HCl to form the corresponding cyclohexanones in moderate-to-good yield with high regioselectivity.

Examples of enantioselective catalysts, including homogeneous supported catalysts and biphasic liquid/liquid, are described and compared. In the case of asymmetric hydride transfer, polythiourea was proven to be more efficient for ruthenium-catalyzed reduction of arylketones, although the iridium complexes gave rise to higher ee when using amino sulfonamide bound to a polystyrene matrix. In the case of asymmetric reduction, the modification of the binap allows the formation of a polymer that could be used as a catalyst precursor and exhibits enantioselectivities as high as observed in solution, but easier to separate and recycle. Bisoxazoline bound to silica particules could also be used in copper-catalyzed asymmetric Diels-Alder reaction and cyclopropanation with selectivities similar to that obtained in solution.

Tricarbonylchromium-mediated dearomatization provides a rapid access to substituted cyclohexadienes. Efficient asymmetric routes to planar chiral arene complexes and to substituted cyclohexadienes have been developed. The article sums up the main features of this chemistry. Highly enantiomerically enriched ortho -substituted benzaldehyde complexes are accessible via asymmetric lithiation followed by trapping with electrophiles. In different solvents, the trimethylsilyl complex exhibits [alpha] values ranging from −174 to +108 for the same enantiomer. Details of two asymmetric syntheses of natural products are given: the alkaloid lasubine I starting from a highly enantiomerically enriched planar chiral arene complex and the marine furanosesquiterpene acetoxytubipofuran. The latter is assembled via asymmetric dearomatization of a benzaldehyde imine complex. Other key steps include an Eschenmoser–Claisen rearrangement and a regio- and diastereoselective Pd-catalyzed allylic substitution. The final section deals with labile arene metal complexes. For the first time, dearomatization reactions mediated by the Mo(CO) 3 group have been realized. The reactions show strong analogies to the Cr(CO) 3 -mediated reactions, but exhibit also marked differences: the arene–Mo bond is stronger, but more labile, and the sequential double additions show different selectivities compared to the chromium analogs.