Marko Hapke

The fascinating construction of pyridine ring systems by transition metal-catalysed [2 + 2 + 2] cycloaddition reactions.

Cycloaddition reactions compose one of the most important classes of reactions when it comes to the simultaneous formation of several bonds in one reaction step. The de novo construction of carbocyclic aromatic systems from acetylenes was also found as an excellent possibility for the assembly of heteroaromatic systems. The transition metal-catalysed [2 + 2 + 2] cycloaddition reaction constitutes a fascinating tool for the synthesis of pyridines from nitriles and the most recent developments demonstrate the ability to control the substitution pattern as well as the possibility of introducing chirality by the use of achiral substrates and a chiral catalyst under mild conditions. In this tutorial review we are focusing on the de novo construction of pyridine ring systems by the transition metal-catalysed [2 + 2 + 2] cycloaddition reaction. After surveying the mechanistic features and intermediates of the reaction depending on the different metal complexes used, we depict the preparation of achiral pyridine derivatives. The last section describes the advances in the synthesis of chiral pyridines and biaryls using the cyclotrimerization method. The various possibilities of introducing chirality by catalytic means are presented and illustrated by instructive examples. This review will be of interest for people active in: Organic Chemistry, Organometallic Chemistry, Transition Metal Chemistry, Stereoselective Synthesis, Heterocyclic Chemistry.

Metal-free cyclotrimerization for the de novo synthesis of pyridines.

The de novo synthesis of pyridines from smaller molecules has attracted a lot of interest since pyridine is one of the most important heterocyclic structural motifs in numerous areas of organic chemistry. Many developed syntheses, such as the Kr hnke or the Hantzsch reaction, rely on condensation reactions of smaller molecules, but a number of synthetic approaches including cycloaddition reactions have also been documented. Over the last few decades the use of transitionmetal-catalyzed transformations of rather simple alkynes and nitriles to generate pyridines has led to the establishment of the [2+2+2] cycloaddition as an efficient tool to even access complex organic frameworks containing pyridine rings. The cross-cyclotrimerization reaction, which leads to pyridines, can be catalyzed by a large range of early to late transition metals; sometimes, however, two metals are needed to complete the cyclization. The formal mechanism of the reaction comprises two consecutive steps for the intraas well as the intermolecular case. In the first step two alkynes or a diyne are oxidatively cyclized to give a metallacyclopentadiene. The second step can be imagined as either an insertion or a [4+2] cycloaddition reaction with a nitrile, after which the formation of the pyridine is complete. While the exclusively intramolecular construction of arenes from tethered triynes or cyanodiynes by transitionmetal catalysis is well known, the uncatalyzed reactions, especially of the latter, have not so far been investigated. The thermal reaction of different triynes at rather high temperatures (up to 200 8C) in a microwave indeed yields the expected tricyclic arenes in up to 87% yield. However, Sakai and Danheiser have now described an interesting version of the uncatalyzed formal [2+2+2] cycloaddition of cyanodiynes that yields functionalized pyridines. The transformation is based on pericyclic cascade reactions and requires thermal energy to proceed successfully, with reaction temperatures higher than 115 8C needed. In a preceding publication, Danheiser and co-workers investigated the formal metal-free, bimolecular [2+2+2] cycloaddition reaction of diynes with electron-deficient alkenes and alkynes (Scheme 1). These investigations led to the proposal that a

Fine‐Tuning the Reactivity and Stability by Systematic Ligand Variations in CpCoI Complexes as Catalysts for [2+2+2] Cycloaddition Reactions

CpCo(I)-olefin-phosphite and CpCo(I)-bisphosphite complexes were systematically prepared and their reactivity in [2+2+2] cycloaddition reactions compared with highly active [CpCo(H(2)C=CHSiMe(3))(2)] (1). Whereas 1 is an excellent precursor for the synthesis of [CpCo(olefin)(phosphite)] complexes (2 a-f), [CpCo(phosphite)(2)] complexes (3 a-e) were prepared photochemically from [CpCo(cod)]. The complexes were evaluated in the cyclotrimerization reaction of diynes with nitriles yielding pyridines. For [CpCo(olefin)(phosphite)], as well as some of the [CpCo(phosphite)(2)] complexes, reaction temperatures as low as 50 °C were sufficient to perform the cycloaddition reaction. A direct comparison showed that the order of reactivity for the complex ligands was olefin(2)>olefin/phosphite>phosphites(2). The complexes with mixed ligands favorably combine reactivity and stability. Calculations on the ligand dissociation from [CpCo(olefin)(phosphite)] proved that the phosphite is dissociating before the olefin. [CpCo(H(2)C=CHSiMe(3)){P(OPh)(3)}] (2 a) was investigated for the co-cyclization of diynes and nitriles and found to be an efficient catalyst at rather mild temperatures.

Synthesis of 5-Substituted 2,2′-Bipyridines from Substituted 2-Chloropyridines by a Modified Negishi Cross-Coupling Reaction

A new and practical approach to a number of differently 5-substituted 2,2′-bipyridines starting from substituted 2-chloropyridines has been found through the application of modified Negishi cross-coupling conditions. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Synthesis of Air‐Stable and Recyclable CpCoI‐Complexes

The advances in transition metal-catalysed [2+2+2] cycloaddition reactions of alkynes and heterocumulenes have demonstrated that a vast number of transition metals are able to catalyse this atom-economic cyclotrimerisation reaction. Nevertheless, group 9 transition metals, and especially cobalt, are of particular importance and interest owing to their long-standing history and versatility in this area. The most commonly used cobalt-based complexes such as [CpCo(CO)2] (1) or [CpCo(cod)] (cod = 1,5-cyclooctadiene) require high temperatures, irradiation with light, or both to be activated. Only a few examples such as the Jonas reagent, [CpCo(H2C= CH2)2] or our recently developed catalyst [CpCo(H2C=CHSiMe3)2] [2] are already active at or below room temperature and have found application. However, one disadvantage of all these CpCo systems is their sensitivity towards air, requiring inert handling and reaction conditions. Up to now, only Gandon et al. reported on the preparation and application of air-stable complexes of the type [CpCo(CO)(dialkyl fumarate)] . We recently developed CpCo systems with two different ligands, namely an olefin and a phosphite ligand, representing a novel class of catalysts that are both reactive and stable complexes. These systematic studies corroborated the advantages heteroleptic ligand combinations can provide for the properties of transition metal precatalysts. The phosphite– olefin combination proved especially advantageous because it principally allowed the variation of the electronic s donor/p acceptor abilities and steric demands of each type of ligand. To further expand the library of these [CpCo(olefin)(phosphite)] compounds and to unearth novel interesting properties, we set out to synthesise complexes with different olefin–phosphite combinations. Especially electron-poor olefins, displaying improved p acceptor abilities, should provide a higher stability for the precatalyst owing to tighter bonding to the metal centre. Initial experiments starting from [CpCo(H2C= CHSiMe3)2] and replacement of the first trimethylvinylsilane ligand for a phosphite P(OR)3 followed by the substitution of the second one for dimethyl fumarate as an electron-deficient olefin at elevated temperatures proceeded only in the case of triphenylphosphite and dimethyl fumarate in excellent yield (98 %). As we intend to establish convenient and efficient synthetic routes for the new complexes, we set forth to pursue a different approach and developed a synthetic strategy starting from the commercially available [CpCo(CO)2] (1) and two successive ligand replacements (Scheme 1). The first CO ligand is easily exchanged for a phosphite ligand by simply stirring

Computational Studies and Experimental Results—An Example of Excellent Teamwork in Studying Carbocyclization

In silico veritas? Maybe not the whole truth, but very helpful suggestions and guidelines for the experimental work can be deduced from computational studies on Rh-catalyzed [3+2+1] cycloaddition reactions for the construction of cis-fused bicyclohexenones from alkylidenecyclopropanes and carbon monoxide.

The broad diversity of CpCo(I) complexes

Abstract The presented review will focus on the systematic overview of the available synthetic approaches and the reactivity and the structural characteristics of selected mononuclear CpCo(I) complexes with (non)chelating neutral donor ligands. The complexes containing symmetrical or unsymmetrical neutral ligand combinations aside from the anionic cyclopentadienyl (Cp) ligand will be discussed and the differences to complexes with substituted Cp ligands will be considered in selected cases.

trans-Di-μ-acetato-[μ-N,N-bis­(diphenyl­phosphino)aniline]bis­[chlorido­molybdenum(II)](Mo—Mo)–dichloro­methane–tetra­hydro­furan (1/0.3/1.7)

The molecular structure of the title compound, [Mo2(CH3COO)2Cl2(C30H25NP2)]·0.3CH2Cl2·1.7C4H8O, features an Mo—Mo dumbbell bridged by two acetate groups which are trans to each other. Perpendicular to the plane spanned by the acetate groups, the Ph2PN(Ph)PPh2 ligand bridges both Mo atoms, having a P—N—P angle of 114.09 (19)°. In a trans position to the PNP ligand are two Cl atoms, one on each molybdenum centre. The Mo—Mo bond distance is 2.1161 (9) Å, within the range known for Mo—Mo quadruple bonds. The Mo complex is located on a crystallographic twofold rotation axis which runs through the N—C bond of the ligand. The site occupation factors of the disordered solvent molecules were fixed to 0.15 for dichloromethane and 0.85 for tetrahydrofuran.

Bis(dimethyl sulfoxide)­hydridobis(triphenyl­phosphane)cobalt(I)

The title compound, [CoH(C18H15P)2(C2H6OS)2], was synthesized by the reaction of chloridotris(triphenylphosphane)cobalt(I), [ClCo(PPh3)3], in the presence of one equivalent potassium hydridotris(pyrazolyl)borate in dimethyl sulfoxide. The structure displays a distorted trigonal-pyramidally coordinated cobalt(I) atom, with two phosphane ligands and one DMSO ligand in the equatorial plane. The coordination is completed by one further DMSO ligand and the anionic hydride in the axial positions.

[N,N-Bis(diphenyl­phosphino)isopropyl­amine]dibromidonickel(II)

The title compound, [NiBr2(C27H27NP2)], was synthesized by the reaction of NiBr2(dme) (dme is 1,2-dimethoxyethane) with N,N-bis(diphenylphosphino)isopropylamine in methanol/tetrahydrofuran. The nickel(II) center is coordinated by two P atoms of the chelating PNP ligand, Ph2PN(iPr)PPh2, and two bromide ions in a distorted square-planar geometry.