Measurement of Nanometer Distances in Solution via 13 C NMR Spectroscopy-Shrinking of Macrocycles with Increasing Temperature.

For a molecular system, size and shape are of elementary importance for its function and properties. Therefore, the determination of distances within a molecule is essential. However, the commonly used methods are only suitable for distances smaller than 4 Šor larger than 15 Å. Here, we show that by incorporating a molecular spring, we can measure distances in macrocycles in the range of 10 Šusing 13 C NMR spectroscopy. The accuracy of the method also allows to determine the temperature dependence of the distances. In one case, we find a contraction of the length by almost 10 % upon heating. This shrinking due to heating can be considered as inverse thermoelasticity at the molecular level and is a previously completely overlooked phenomenon that can be used in the future as a tool to change the length and, thus, the function of a system.

Metal-Catalyzed Haloalkynylation Reactions.

Metal catalysis has revolutionized synthetic chemistry, leading to entirely new, very efficient transformations, which enable access to complex functionalized molecules. One such new transformation method is the haloalkynylation reaction, in which both a halogen atom and an alkynyl unit are transferred to an unsaturated carbon-carbon bond. This minireview summarizes the development of metal-catalyzed haloalkynylation reactions since their beginning about a decade ago. So far, arynes, alkenes and alkynes have been used as unsaturated systems and the reactivities of these systems are summarized in individual chapters of the minireview. Especially, the last few years have witnessed a rapid development due to gold-catalyzed reactions. Here, we discuss how the choice of the catalytic system influences the regio- and stereoselectivity of the addition.

Cyclopropenylmethyl Cation: A Concealed Intermediate in Gold(I)-Catalyzed Reactions.

The last years have witnessed many gold-catalyzed reactions of alkynes. One of the most prominent species in the reaction of two alkyne units is the vinyl-substituted gold vinylidene intermediate. Here, we were able to show that the reaction of a haloacetylene and an alkyne proceeds via a hitherto overlooked intermediate, namely the cyclopropenylmethyl cation. The existence and relative stability of this concealed intermediate is verified by quantum chemical calculations and 13 C-labeling experiments. A comparison between the cyclopropenylmethyl cation and the well-known vinylidene intermediate reveals that the latter is more stable only for smaller cycles. However, this stability reverses in larger cycles. In the case of the smallest representative of both species, the vinylidene cation is the transition state en route to the cyclopropenylmethyl cation. The discovery of this intermediate should help to get a deeper understanding for gold-catalyzed carbon-carbon bond-forming reactions of alkynes. Furthermore, since enynes can be formed from the cyclopropenylmethyl cation, the inclusion of this intermediate should enable the development of new synthetic methods for the construction of larger cyclic halogenated and non-halogenated conjugated enyne systems.

Gold(I)-Catalyzed Haloalkynylation of Aryl Alkynes: Two Pathways, One Goal.

Haloalkynylation reactions provide an efficient method for the simultaneous introduction of a halogen atom and an acetylenic unit. For the first time, we report a gold(I)-catalyzed haloalkynylation of aryl alkynes that delivers exclusively the cis addition product. This method enables the simple synthesis of conjugated and halogenated enynes in yields of up to 90 %. Notably, quantum chemical calculations reveal an exceptional interplay between the place of the attack at the chloroacetylene: No matter which C-C bond is formed, the same enyne product is always formed. This is only possible through rearrangement of the corresponding skeleton. Hereby, one reaction pathway proceeds via a chloronium ion with a subsequent aryl shift; in the second case the corresponding vinyl cation is stabilized by a 1,3-chlorine shift. 13 C-labeling experiments confirmed that the reaction proceeds through both reaction pathways.

1,3-Chlorine Shift to a Vinyl Cation: A Combined Experimental and Theoretical Investigation of the E-Selective Gold(I)-Catalyzed Dimerization of Chloroacetylenes.

Metal-catalyzed dimerization reactions of terminal acetylenes are well known in the literature. However, only a few examples of the dimerization of halogen-substituted acetylenes are described. The products of the latter metal-catalyzed dimerization are the branched head-to-tail enynes. The formation of the corresponding linear head-to-head enynes has not been reported yet. Herein, we demonstrate by means of quantum chemical methods and experiments that the head-to-head dimerization of chloroarylacetylenes can be achieved via mono gold catalysis. Under the optimized conditions, a clean and complete conversion of the starting materials is observed and the dimeric products are obtained up to 75% NMR yield. A mechanistic investigation of the dimerization reaction reveals that the branched head-to-tail vinyl cation is energetically more stable than the corresponding linear head-to-head cation. However, the latter can rearrange by an unusual 1,3-chlorine shift, resulting in the highly stereoselective formation of the trans product, which corresponds to the gold complex of the head-to-head E-enyne. The activation barrier for this rearrangement is extremely low (ca. 2 kcal/mol). As the mono gold-catalyzed dimerization can be conducted in a preparative scale, this simple synthesis of trans-1,2-dichloroenynes makes the gold(I)-catalyzed head-to-head dimerization of chloroarylacetylenes an attractive method en route to more complex conjugated enyne systems and their congeners.

Linear Relationship between 13 C†NMR Chemical Shifts and the Bending of sp-Carbon Chains.

Polyynes show a strictly linear relationship between the energy impact and the bending of the polyyne chain. The energy, which is necessary to bend the acetylenic chain, decreases with the increasing number of acetylene units. A deviation from linearity in polyynes can be realized in solution by violation of the mutual-exclusion principle between IR and Raman spectra. However, there is still no possibility to measure the extent of the nonlinearity in solution. Herein, we show that the 13 C NMR spectroscopy represents an appropriate tool for this as we found an almost perfect linear relationship between the bending of the alkyne chain and the change of the chemical shift of the outer acetylenic carbon atoms. By using molecular bows in which the alkyne chain can be bent by switching the azobenzene unit, this correlation can be proved experimentally. In the future, this correlation should enable the determination of the extent of the bending and the strain energy in polyynes. Consequently, polyynes could be employed as probes for measuring further molecular forces.

Gold(I)-Catalyzed Chloroalkynylation of 1,1-Disubstituted Alkenes via 1,3-Chlorine Shift: A Combined Experimental and Theoretical Study.

The haloalkynylation reaction is of great interest for the synthesis of complex molecules as it represents a carbon-carbon bond-forming reaction where the reactive halide reappears in the product. The latter enables further chemical transformations. However, only a few examples of haloalkynylations have been described so far. By using alkenes as reactant, this reaction is strictly limited to norbornene systems proceeding via a nonclassical carbocation. Herein, we show by means of quantum chemical calculations and experiments that the chloroalkynylation of 1,1-disubstituted alkenes can be successfully achieved via gold(I) catalysis. The key step in the reaction mechanism is a 1,3-chlorine shift to a cationic center, leading selectively to the corresponding homopropargyl chlorides. As this gold(I)-catalyzed addition can be conducted on a preparative scale and tolerates a broad substrate scope of both alkyne and alkene reactants, the presented chloroalkynylation reaction is an attractive method en route to complex alkynes and their congeners.

Dimerization of Substituted Arylacetylenes-Quantum Chemical Calculations and Kinetic Studies.

The dimerization of substituted arylacetylenes is a very interesting tool to generate 1,3-butadiene 1,4-diradicals. Recently, it was shown that electron-withdrawing groups attached to the triple bond reduce the activation barrier and increase the stability of the diradical intermediates. Here, we investigate the influence of the π donor character of substituents, which are bound to the aryl system, on the dimerization reaction of arylacetylenes. Both quantum chemical calculations and kinetic studies reveal that the higher the π donor character of substituents, the lower the activation barrier. The highest observed difference between the model systems amounts to 4.0 kcal/mol, which represents an acceleration by a factor of 700. However, according to the calculations the π donor character of the substituents increases the diradical character of the intermediates.

Au(I)-Catalyzed Dimerization of Two Alkyne Units-Interplay between Butadienyl and Cyclopropenylmethyl Cation: Model Studies and Trapping Experiments.

In recent years, Au(I)-catalyzed reactions proved to be a valuable tool for the synthesis of substituted cycles by cycloaromatization and cycloisomerization starting from alkynes. Despite the myriad of Au(I)-catalyzed reactions of alkynes, the mono Au(I)-catalyzed pendant to the radical dimerization of nonconjugated alkyne units has not been investigated by quantum chemical calculations. Herein, by means of quantum chemical calculations, we describe the mono Au(I)-catalyzed dimerization of two alkyne units as well as the transannular ring closure reaction of a nonconjugated diyne. We found that depending on the system and the method used either the corresponding cyclopropenylmethyl cation or the butadienyl cation represents the stable intermediate. This circumstance could be explained by different stabilizing effects. Moreover, the calculation reveals a dramatic (>1012-fold) acceleration of the Au(I)-catalyzed reaction compared to that of the noncatalyzed radical variant. Trapping experiments with a substituted 1,6-cyclodecadiyne using benzene as a solvent at room temperature as well as studies with deuterated solvents confirm the calculations. In this context, we also demonstrate that trapping of the cationic intermediate with benzene does not proceed via a Friedel-Crafts-type reaction.