Asymmetric cobalt-catalyzed Diels-Alder reactions of a boron-functionalized 1,3-diene with alkynes and allylboration with aldehydes

[Structure: see text] A cobalt(I)-catalyzed Diels-Alder reaction of a 1-boron-functionalized 1,3-diene is the key step in a one-pot reaction interconnecting three simple starting materials to obtain a multifunctionalized product. This product incorporates a stereogenic quaternary center next to a stereogenic secondary alcohol functionality generated with a very high degree of regio- and diastereoselectivity and good enantioselectivity in the presence of a chiral ligand such as (S,S)-Norphos.     

Regioselective cobalt-catalyzed addition of sulfides to unactivated alkenes

A novel method to synthesize tertiary alkyl/aryl sulfides in a mild and regioselective manner from unactivated alkenes using cobalt catalysis is described. The methodology is compatible with sensitive functionalities and is successful with several different types of alkenes and sulfides.     

Regioselective cobalt-catalyzed formation of bicyclic 3- and 4-aminopyridines

Bimolecular cobalt-catalyzed [2 + 2 + 2] cycloadditions between yne-ynamides and nitriles afford bicyclic 3- or 4-aminopyridines in up to 100% yield. The high regioselectivity observed depends on the substitution pattern at the starting ynamide. Aminopyridines bearing TMS and Ts groups are efficiently deprotected in an orthogonal fashion.     

Regioselective entry to bromo-gamma-hydroxybutenolides: useful building blocks for assemblying natural product-like libraries

[reaction: see text] We report a regioselective entry to 3-bromo- and 4-bromo-5-hydroxy-5H-furan-2-ones by photooxidation of 3-bromofuran with a singlet oxygen in the presence of a suitable base. By this procedure, a variety of 3-substituted gamma-hydroxybutenolides have become for the first time easily accessible. Strategies employing these highly functionalized building blocks for the preparation of focused libraries of natural-like molecules are also discussed.     

Synthesis of tetrazolopiperazine building blocks by a novel multi-component reaction

A novel Ugi-five-centre-four-component reaction (U-5C-4CR) of aldehydes, primary amines, trimethylsilylazide and 2-isocyanoethyltosylate yielding tetrazolopiperazine building blocks is described.     

Macrocycles from simple building blocks by a multifold Heck-type coupling reaction

Diiodobenzenes and bisallylic alcohols—two equivalents of each—were coupled under palladium catalysis to give oxofunctionalized macrocycles as 2:2 products. The 1:1 products as medium sized rings were disfavoured and not observed.     

Organosilatrane building blocks

Phenylsilatrane analogues containing reactive amino, bromo, boronic ester, and alkynyl functional groups for coupling reactions have been prepared. Pinacol boronic ester and ethynyl analogues were synthesized from 4-bromophenylsilatrane by palladium catalyzed reactions. The silatrane functional group was shown to be stable during the palladium catalysis procedures and silica-gel purification, making the molecules amenable to further synthetic manipulation. The described phenylsilatranes are useful building blocks for forming more complex organosilatrane species.     

Multi-component regio- and diastereoselective cobalt-catalyzed hydrovinylation/allylboration reaction sequence

The combination of a regioselective cobalt-catalyzed 1,4-hydrovinylation and the diastereoselective allylboronation reaction leads to a wide scope of functionalized hydroxydienyl esters in a one-pot reaction in excellent yields. With catalytic amounts of base, these products are easily converted either into α,β,γ,δ-unsaturated hydroxyl esters or complex tetrasubstituted tetrahydropyrans in chemo- and diastereoselective fashions. In addition, a high-yielding four-component one-pot reaction involving an acrylate, two different and unsymmetrical 1,3-dienes, and an unsaturated aldehyde is presented.     

Encoded dendrimers with defined chiral composition via'click' reaction of enantiopure building blocks

Dendrimers with end-groups of defined chiral composition have been prepared from alkyne functional enantio-pure building blocks obtained by selective enzymatic (ADH) ketone reductions using click chemistry. Optical rotation and enantioselective enzymatic modification is in agreement with the chiral composition of the dendrimers and permits unique molecular-level encoding of stereoisomeric dendritic libraries.     

Biorenewable and mercaptoacetylating building blocks in the Biginelli reaction: synthesis of thiosugar-annulated dihydropyrimidines

A novel version of the Biginelli reaction using an unprotected aldose as a biorenewable aldehyde component and 2-methyl-2-phenyl-1,3-oxathiolan-5-one as a mercaptoacetylating active methylene building block with urea/thiourea is reported. The reaction is nanoclay-catalysed, expeditious and effected under solvent-free microwave irradiation conditions in a one-pot procedure to yield diastereoselectively, thiosugar-annulated multifunctionalized dihydropyrimidines via intramolecular domino cyclocondensation reactions of an isolable intermediate.     

Sequential Birch reaction and asymmetric Ir-catalyzed hydrogenation as a route to chiral building blocks

A range of 1,2,4-trisubstituted cyclohexadienes obtained from the Birch reaction were hydrogenated asymmetrically to produce synthetically valuable chiral compounds in high enantio- and diastereoselectivity.     

Convenient synthesis of alkylhydrazides by the cobalt-catalyzed hydrohydrazination reaction of olefins and azodicarboxylates

Treatment of olefins 2 with 1.5 equiv of di-tert-butyl azodicarboxylate (3), 1 equiv of PhSiH3, and 1.5-5 mol % of the simple Co(III) catalyst 1 in ethanol at 23 degrees C affords the Markovnikov hydrazide product for a broad range of olefins in 62-94% yield.     

Studies directed toward the development of amide-linked RNA mimics: synthesis of the monomeric building blocks

A general approach toward the synthesis of all four monomeric building blocks of the ribonucleoside amino acids 3'-amino-5'-carboxymethyl-3',5'-dideoxy nucleosides in their protected forms is described that will facilitate the development of amide-linked RNA mimics.     

Synthesis of lipophilic bisanthracene fluorophores: versatile building blocks toward the synthesis of new light-harvesting dendrimers

Lipophilic bisanthracene-based fluorophore and its derivatives were synthesized by the Suzuki-Miyaura cross-coupling reaction of 9-anthrylboronic acid with a substituted dibromobenzene. In addition to desirable fluorescent properties, these molecular systems were demonstrated to serve as versatile building blocks toward the synthesis of two types of new light-harvesting dendrimers due to their chemical stability.     

Ligand-tuned regioselectivity of a cobalt-catalyzed Diels-Alder reaction. A theoretical study

Quantum chemical calculations at the BP86/def2-SVP levels of theory have been carried out for the reaction pathways of the [Co(L)] (+)-catalyzed Diels-Alder reaction of isoprene with phenylacetylene, with L = dppe, iminA, iminB. The calculations suggest that the reactions take place in a stepwise fashion, starting with the formation of the complex [Co(L)(isoprene)(phenylacetylene)] (+) as precursor for the consecutive C-C bond formation. The actual Diels-Alder ring-closing reaction proceeds as an intramolecular addition of the ligands isoprene and phenylacetylene, yielding a metallacyclic intermediate after generation of the first carbon-carbon bond, which determines the regioselectivity of the reaction. There are four different conformations of the starting complexes [Co(L)(isoprene)(phenylacetylene)] (+) which initiate four different pathways yielding the 1,3-cyclohexadiene product. The energetically most stable conformations do not lead to the reaction pathways that have the lowest activation energies. All conformations and the associated pathways must be considered in order to obtain the kinetically most favorable reaction course. The calculated values for the regioselectivities of the [Co(L)] (+)-catalyzed Diels-Alder reaction agree exceptionally well with the experimental values. The calculations concur with the experimental finding that the para product is kinetically favored for L = dppe while the formation of the meta product is kinetically favored when L = iminA or iminB. The different regioselectivies for L = dppe and L = iminA or iminB come from (a) the steric interactions of the bidentate ligands with the isoprene and phenylacetylene moieties in [Co(L)(isoprene)(phenylacetylene)] (+), which determine the distance between the carbon atoms forming the C-C bond, and (b) the relative energies of the different starting complexes. The first C-C bond formed in the rate-determing step of the [Co(dppe)] (+)-catalyzed reaction yielding the para product is the C4-C1' bond, and for the meta product it is the C1-C1' bond. The opposite order is found for the [Co(iminA)] (+)- and [Co(iminB)] (+)-catalyzed reactions, where the C1-C2' bond formation is the initial step toward the para product, while the C4-C2' bond is first formed in the reaction yielding the meta product. The calculations suggest that a less polar solvent should reduce the preference for formation of the meta product in the [Co(iminA)] (+)- and [Co(iminB)] (+)-catalyzed reactions but would enhance the formation of the para product in the [Co(dppe)] (+)-catalyzed reaction. Experimental tests using toluene as solvent instead of dichloromethane confirm the theoretical predictions.     

Regioselective reaction of ortho-piperidinobenzaldehydes with pyrazolone

Cyclization of 2-(4-R-piperidino)benzaldehydes with 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one proceeding via tert-amino effect mechanism is stereoselective. Relative configuration of (3R*,4aS*,5R*)-2,3,4,4a,5,6-hexahydro-1H-benzo[c]quinolizine was established on the base of NMR spectroscopy data and X-ray analysis.     

Gaining absolute control of the regiochemistry in the cobalt-catalyzed 1,4-hydrovinylation reaction

The absolute control of the regiochemistry of a cobalt-catalyzed 1,4-hydrovinylation reaction is achieved by alternation of the ligands applied. While the dppe/dppp ligands led to the formation of the branched product, the herein described application of the SchmalzPhos ligand generates the corresponding linear product in both excellent yields and regioselectivities. The catalyst system exhibits a high tolerance toward functional groups, and the very mild reaction conditions allow the synthesis of 1,4-dienes without isomerization into conjugated systems.     

W6S8] octahedral tungsten clusters functionalized with thiophene derivatives: toward polymerizable building blocks

The functionalization of octahedral [W(6)S(8)] clusters with a family of phosphino-thiophene ligands has been investigated with the goal of synthesizing extended networks of [W(6)S(8)] units covalently linked to one another through thiophene-conjugated bridges. In addition to new phosphino-thiophene ligands, eight clusters were synthesized and characterized by (1)H and (31)P NMR spectroscopies, elemental analysis, and UV-vis absorption. These clusters are formulated [W(6)S(8)(T-PPh(2))6] (1a), [W(6)S(8)(T-PEt(2))(6)] (1b), [W(6)S(8)(2T-PPh(2))(6)] (2a), [W(6)S(8)(2T-PEt(2))(6)] (2b), [W(6)S(8)(3T-PPh(2))(6)] (3a), [W(6)S(8)(3T-PEt(2))(6)] (3b), [W(6)S(8)((2T)(3)P)(6)] (4), and [W(6)S(8)(2EDOT-PEt(2))(6)] (5) (T = thiophene and EDOT = 3,4-ethylenedioxythiophene). The molecular structure of six of them has been obtained by single-crystal X-ray diffraction analysis. All of them crystallize in the P1 triclinic space group except 3b, which has the P2(1)/c monoclinic symmetry. The redox behavior of both the ligands and the corresponding functionalized clusters has been investigated by cyclic voltammetry. An attempt to electropolymerize these species is also reported.     

Metal-substituted Ti8C12 metallocarbohedrynes: toward less reactive clusters as building blocks of cluster-assembled materials

To form cluster-assembled materials, the clusters should have low reactivity and be characterized by a closed-shell electronic configuration with a large gap between the highest occupied and the lowest unoccupied molecular orbitals (HOMO-LUMO). Using spin-polarized density functional theory calculations, we investigate the M-substituted Ti(8)C(12) metallocarbohedrynes to search for less reactive clusters as building blocks for cluster-assembled materials (M = Be, Mg, Ca, Sr, Ba and Sc, Y). The selected atoms in the correct stoichiometry would produce a metallocarbohedryne that is isoelectronic with the Ti(8)C(12)(2+), which has a closed-shell electronic configuration and an enhanced HOMO-LUMO gap of 1.735 eV. According to our results, the HOMO-LUMO gaps of the M-substituted Ti(8)C(12) metallocarbohedrynes are in the range of 0.715-0.979 eV for the case of Be, Mg, Ca, Sr and Ba and in the range of 0.865-1.294 eV for the case of Sc and Y. Among all the M-substituted metallocarbohedrynes we consider here, one of the isomers of Ti(6)Sc(2)C(12) is not only energetically more favorable but also exhibits a larger HOMO-LUMO gap of 1.294 eV. This result indicates that the Ti(6)Sc(2)C(12)(4) metallocarbohedryne should be less reactive than the Ti(8)C(12) metallocarbohedryne which has a narrow HOMO-LUMO gap of 0.146 eV. Moreover, we show that the intercluster interaction between two individual Ti(6)Sc(2)C(12)(4) metallocarbohedrynes is relatively weak compared to the Ti(8)C(12) dimer.     

Supramolecular architectures from phthalocyanine building blocks

Different procedures for preparing columnar stacks and layered structures from phthalocyanine molecules are presented and discussed, including organization of the molecules by one of the following means: (i) with the help of liquid crystallinity, (ii) by using crown ether rings attached to the phthalocyanine core, (iii) by polymerization, and (iv) by Langmuir-Blodgett film formation.