Asymmetric synthesis of benzylic and heterobenzylic amines

C2-Symmetrical, enantiopure 2,6-di[1-(1-aziridinyl)alkyl]pyridines (DIAZAPs) were prepared by a high-yielding, three-step sequence starting from 2,6-pyridinedicarbaldehyde and (S)-valinol or (S)-phenylglycinol. The new compounds were tested as ligands in palladium-catalyzed allylation of carbanions in different solvents. Almost quantitative yield and up to 99% enantiomeric excess were obtained in the reactions of the enolates derived from malonate, phenyl- and benzylmalonate dimethyl esters with 1,3-diphenyl-2-propenyl ethyl carbonate. Asymmetric synthesis of 2-(2-pyridyl)aziridines from chiral 2-pyridineimines bearing a stereogenic center at the nitrogen atom was development. The envisioned route involves the addition of chloromethyllithium to the imine derived from 2-pyridinealdehyde and (S)-valinol, protected as O-trimethylsilyl ether. The analogous reaction performed on the imine derived from (S)-valine methyl ester gave the product containing the aziridine ring as well as the α-chloro ketone group coming from the attack of chloromethyllithium to the ester function. Other stereogenic alkyl substituents at nitrogen gave less satisfactory results. Moreover, the aziridination protocol did not work on other aromatic imines, e.g. 3-pyridineimine and benzaldimine, which are not capable of bidentate chelation. The N-substituent could not be removed, but aziridine underwent ring-opening by attack of nitrogen, sulfur, and oxygen nucleophiles. Complete or prevalent regioselectivity was obtained using cerium trichloride heptahydrate as a catalyst. In some cases, the N-substituent could be removed by an oxidative protocol. The addition of organometallic (lithium, magnesium, zinc) reagents to 2-pyrroleimines derived from (S)-valinol and (S)-phenylglycinol gave the N-substituted-1-(2-pyrrolyl)alkylamines with high yields and diastereoselectivities. The (S,S)-diastereomers were useful intermediates for the preparation of enantiopure 1-[1-(2-pyrrolyl)alkyl]aziridines by routine cyclization of the β-aminoalcohol moiety and of (S)-N-benzoyl 1-[1-(2-pyrrolyl)alkyl]amines and their N-substituted derivatives by oxidative cleavage of the chiral auxiliary. 1-Allyl-2-pyrroleimines obtained from (S)-phenylglycinol and (S)-valinol underwent highly diastereoselective addition of allylmetal reagents, used in excess amounts, to give the corresponding secondary amines with concomitant allyl to 1-propenyl isomerisation of the 1-pyrrole substituent. Protection of the 2-aminoalcohol moiety as oxazolidinone, amide or Boc derivate followed by ring closing metathesis of the alkene groups gave the unsaturated bicyclic compound, whose hydrogenation afforded the indolizidine derivative as a mixture of separable diastereomers. The absolute configuration of the main diastereomer was assessed by X-ray crystallographic analysis.

Materiali Politiofenici Otticamente Attivi

Much effort has been devoted in the recent years to the investigation of optically active polythiophenes characterized by the presence of a chiral moiety linked to the 3-position of the aromatic ring. In addition to their potential technological applications as materials for enantioselective electrodes and membranes, chiral poly(thiophene)s offer the possibility of studying the structural changes accompanying the transition from the disordered state by following the variation of their chiroptical properties by circular dichroism (CD). In solution of a good solvent, that kind of polythiophenes doesn’t display any optical activity arising from the presence of dissymmetric conformation of the backbone, as shown by circular dichroism (CD) spectra. When the macromolecules begin to aggregate, as it occurs e.g. by addition of a poor solvent, or lowering the solution temperature, or when the macromolecules are assembled in the solid state as thin films obtained by solution casting or spin coating, significant CD bands are observed in the spectral region related to the electronic absorptions of the aromatic polythiophene chromophore. These CD bands are indicative of a chiral macromolecule arrangement of one prevailing chirality. The synthesis of -substituted polythiophenes can be carried out starting from the corresponding -substituted mono- or oligomeric thiophenic monomers under regioselective or regiospecific conditions in order to minimize or avoid the formation of head-to-head dyads unfavourably affecting the presence of coplanar conformations of thiophene rings as a consequence of steric interactions between the side-chain substituents, both in solution and in the solid state. To this regard, non-symmetrically substituted monomers require therefore to perform the polymerization in the presence of highly demanding catalysts and reaction condition, whereas with symmetrically substituted oligothiophenic monomers containing the -substituents located far apart from the reacting sites, it is instead possible to obtain regioregular macromolecules by adopting more simple and economic polymerization methods, such as, e. g., the chemical oxidative polymerization with iron (III) trichloride. In order to verify how the polymer structure affects its optical activity, further poly-3-alkylthiophenes, substituted by an enantiomerically pure chiral alkyl group, namely poli[3,3”-di[2((S)-(+)-2-methylbutoxy)ethyl]-2,2’:5’,2”-terthiophene] (PDMBOETT), poli[3,3’di[2((S)-(+)-2-methylbutoxy)ethyl]-2,2’-bitiofene] (PDMBOEBT), poli[3,3””-didodecyl-4’,3”’-di(S)-(+)-2-methylbutyl-2,2’:5’,2”:5”,2”’:5”’,2””-quinquethiophene (PDDDMBQT) have been synthesized and characterized by instrumental techniques. The spectroscopic behaviour of thin films of poly(DDDMBQT) has been investigated in the solid state under different sample preparation procedures. It was also compared with the behaviour of polymers previously made. The experimental results are interpreted in terms of influence of the side-chain substituents on the extent of planarity of the polymeric chains and the formation of optically active chiral aggregates. In recent years conjugated block copolymers have received considerable attention. It is well known that conjugated block copolymers composed of two electronically different blocks can have morphologic and optical properties, that differ from those of their homopolymers. A recent study has also shown that the electronic properties and the supramolecular organization of one conjugated block can also be influenced by the other block. In order to study better this behavior, a new conjugated block copolymers, composed of a regioregular hydrophylic block and a regioregular hydrophobic block namely poli[3[2-(2-metossietossi)etossi]metiltiofene]-co- poli[3(1-octilossi)tiofene], has been synthesized and characterized.

N-Heterocyclic carbene complexes of rhodium: structures, dynamics and catalysis

A series of imidazolium salts of the type [BocNHCH2CH2ImR]X (Boc = t-Bu carbamates; Im = imidazole) (R = Me, X = I, 1a; R = Bn, X = Br, 1b; R = Trityl, X = Cl, 1c) and [BnImR’]X (R’ = Me, X = Br, 1d; R’ = Bn, X = Br, 1e; R’ = Trityl, X = Cl, 1g; R’ = tBu, X = Br, 1h) bearing increasingly bulky substituents were synthetized and characterized. Subsequently, these precursors were employed in the synthesis of silver(I)-N-heterocyclic (NHC) complexes as transmetallating reagents for the preparation of rhodium(I) complexes [RhX(NBD)(NHC)] (NHC = 1-(2-NHBoc-ethyl)-3-R-imidazolin-2-ylidene; X = Cl; R = Me, 4a; R = Bn, 4b; R = Trityl, 4c; X = I, R = Me, 5a; NHC = 1-Bn-3-R’-imidazolin-2-ylidene; X = Cl; R’ = Me, 4d, R’ = Bn, 4e, R’ = Trityl, 4g; R’ = tBu, 4h). VT NMR studies of these complexes revealed a restricted rotation barriers about the metal-carbene bond. While the rotation barriers calculated for the complexes in which R = Me, Bn (4a,b,d,e and 5a) matched the experimental values, this was not true for the complexes 4c,g, bearing a trityl group for which the values are much smaller than the calculated ones. Energy barriers for 4c,g, derived from a line shape simulation, showed a strong dependence on the temperature while for 4h the rotational energy barrier is stopped at room temperature. The catalytic activity of the new rhodium compounds was investigated in the hydrosilylation of terminal alkynes and in the addition of phenylboronic acid to benzaldehyde. The imidazolium salts 1d,e were also employed in the synthesis of new iron(II)-NHC complexes. Finally, during a six-months stay at the University of York a new ligand derived from Norharman was prepared and employed in palladium-mediated cross-coupling.

New and More Sustainable Processes for the Synthesis of Phenolics: 2-phenoxyethanol and hydroxytyrosol

The research work has dealt with the study of new catalytic processes for the synthesis of fine chemicals belonging to the class of phenolics, namely 2-phenoxyethanol and hydroxytyrosol. The two synthetic procedures investigated have the advantages of being much closer to the Green Chemistry principles than those currently used industrially. In both cases, the challenge was that of finding catalysts and methods which led to the production of less waste, and used less hazardous chemicals, safer solvents, and reusable heterogeneous catalysts. In the case of 2-phenoxyethanol, the process investigated involves the use of ethylene carbonate (EC) as the reactant for phenol O-hydroxyethylation, in place of ethylene oxide. Besides being a safer reactant, the major advantage of using EC in the new synthesis is the better selectivity to the desired product achieved. Moreover, the solid catalyst based on Na-mordenite was fully recyclable. The reaction mechanism and the effect of the Si/Al ratio in the mordenite were investigated. In the case of hydroxytyrosol, which is one of the most powerful natural antioxidants, a new synthetic procedure was investigated; in fact, the method currently employed, the hydrolysis of oleuropein, an ester extracted from the waste water processing of the olive, makes use of large amounts of organic solvents (hexane, ethyl acetate), and involves several expensive steps of purification. The synthesis procedure set up involves first the reaction between catechol and 2,2-dimethoxyacetaldehyde, followed by the one-pot reduction of the intermediate to give the desired product. Both steps were optimized, in terms of catalyst used, and of reaction conditions, that allowed to reach ca 70% yield in each step. The reaction mechanism was investigated and elucidated. During a 3-month period spent at the University of Valencia (with Prof. A. Corma’s group), a process for the production of diesel additives (2,5-bis(propoxymethyl)furan) from fructose has been investigated.