Computational and DNMR Analysis of the Conformational Isomers and Stereodynamics of Secondary 2,2'-Bisanilides.

The conformational preference of 2,2'-bisanilides was investigated by variable-temperature NMR spectroscopy, NMR titration and diffusion experiments, IR spectroscopy, computational analysis, and X-ray crystallography. The formation of a conformation having the two amide moieties linked by an intramolecular hydrogen bond was detected at low temperatures. The interconversion kinetics of the two conformational species of bisanilide 2 were determined by NMR line shape analysis. The formation of a supramolecule linked by intermolecular hydrogen bonds was ruled out by means of DMSO titration, DOSY experiments, and steric considerations.

Computational and DNMR investigation of the isomerism and stereodynamics of the 2,2'-binaphthalene-1,1'-diol scaffold.

The relative stabilities of three conformational isomers of 2,2'-binaphthalene-1,1'-diol diisobutyrate and the energy barriers to rotation about the pivotal aryl-aryl bond and the two aryl-oxygen bonds were investigated by variable-temperature NMR spectroscopy in conjunction with DFT computations. The experimental and calculated data were found to be in very good agreement and provide new insights into the dynamic stereochemistry of BINOL-derived tropos ligands.

The experimental observation of the intramolecular NO2/CO interaction in solution.

The weak electrostatic interaction between nitro and carbonyl moieties has been observed by means of variable-temperature NMR spectroscopy. Its energetic contribution was evaluated to be about 3 kcal mol(-1) by DFT calculations, and confirmed by the measurement of internal energy barriers to the rotation of suitable nitroaryl rings.

New developments in gold-catalyzed manipulation of inactivated alkenes.

Over the recent years, the nucleophilic manipulation of inactivated carbon-carbon double bonds has gained remarkable credit in the chemical community. As a matter of fact, despite lower reactivity with respect to alkynyl and allenyl counterparts, chemical functionalization of isolated alkenes, via carbon- as well as hetero atom-based nucleophiles, would provide direct access to theoretically unlimited added value of molecular motifs. In this context, homogenous [Au(I)] and [Au(III)] catalysis continues to inspire developments within organic synthesis, providing reliable responses to this interrogative, by combining crucial aspects such as chemical selectivity/efficiency with mild reaction parameters. This review intends to summarize the recent progresses in the field, with particular emphasis on mechanistic details.

Mechanistic insights into enantioselective gold-catalyzed allylation of indoles with alcohols: the counterion effect.

Enantioselective gold-catalysis is emerging as a powerful tool in organic synthesis for the stereoselective manipulation of unfunctionalized unsaturated hydrocarbons. Despite the exponential growth, the molecular complexity of common chiral gold complexes generally prevents a complete description of the mechanism steps and activation modes being documented. In this study, we present the results of a combined experimental-computational (DFT) investigation of the mechanism of the enantioselective gold-catalyzed allylic alkylation of indoles with alcohols. A stepwise S(N)2'-process (i.e. anti-auroindolination of the olefin, proton-transfer, and subsequent anti-elimination [Au]-OH) is disclosed, leading to a library of tricyclic-fused indole derivatives. The pivotal role played by the gold counterion, in terms of molecular arrangement (i.e. "folding effect") and proton-shuttling in restoring the catalytic species, is finally documented.

One-pot gold-catalyzed synthesis of azepino[1,2-a]indoles.

Indoles from scratch: A gold(I)/N-heterocyclic carbene complex (IPr=1,3-di(isopropylphenyl)imidazol-2-ylidene) was found to be particularly effective as a catalyst, enabling the one-pot synthesis of tricyclic azepinoindoles by an unprecedented cascade reaction. Readily available substrates, high chemoselectivity, good yields, and water as the only stoichiometric by-product are some of the main advantages of this method.

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols.

Gold(I)-N-heterocyclic carbene (NHC) complexes proved to be a reliable catalytic system for the direct synthesis of functionalized γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with primary alcohols. Good isolated chemical yields were obtained for a range of malonyl and acetate derivatives. The good performance in reagent-grade solvents and the functional group/moisture tolerance make this catalytic process a promising route for the synthesis of architecturally complex polycyclic structures.

Enantioselective gold-catalyzed synthesis of polycyclic indolines.

The synthesis of architecturally complex polycyclic fused indolines is achieved in a chemo-, regio-, and stereodefined manner, via an enantioselective gold-catalyzed cascade hydroindolination/iminium trapping synthetic sequence. Highly functionalized tetracyclic fused furoindolines (2) and dihydropyranylindolines (4) are synthesized in moderate to good yields and enantiomeric excesses of up to 87%.