Recent progress in the field of asymmetric organocatalytic 1,4-conjugate addition reactions, regarded as belonging among the more synthetically important carbon-carbon bond-forming reactions, is described. The focus is on some recent advances in the following selected reactions: additions of various nucleophiles to α,β-unsaturated cyclic and acyclic

Spontaneous symmetry breaking in reactive systems, known as a rare physical phenomenon and for the Soai autocatalytic irreversible reaction, might in principle also occur in other, more common asymmetric reactions when the chiral product is capable to promote its formation and an element of "nonlinearity" is involved in the reaction scheme. Such phenomena are long sought after in chemistry as a possible explanation for the biological homochirality of biomolecules. We have investigated homogeneous organic stereoselective Mannich and Aldol reactions, in which the product is capable to form H-bridged complexes with the prochiral educt, and found by applying NMR spectroscopy, HPLC analysis, and optical rotation measurements 0.3-50.8% of random product enantiomeric excess under essentially achiral reaction conditions. These findings imply a hitherto overlooked mechanism for spontaneous symmetry breaking and, hence, a novel approach to the problem of absolute asymmetric synthesis and could have also potential significance for the conundrum of homochirality.

Möbius aromaticity, predicted by Edgar Heilbronner in 1964, is a stabilizing effect exhibited by 4n electron fully conjugated cyclic molecules (or transition states) with an odd number of orbital phase inversions. Although it has previously been suggested that this effect might also apply to planar metallacycles in which a transition metal employs a d orbital in delta-type binding mode, only very few examples of stable twisted molecules composed of main group elements are known. We report herein, the first computationally confirmed 4npi aromatic planar metallacyclic examples and their building principles. Aromatic stabilization energy (ASE) of a 8pi metalla-cycloheptatriene [Fe(CH)(6)H(2)], with four doubly occupied pi orbitals and a HOMA value of +0.80 (cf. benzene=+1.0), an NICS(0) value of -8.5 (benzene=-9.8, NICS=nucleus independent chemical shift), and with one phase inversion, is +27.5 kcal mol(-1) (about two-thirds of the value for benzene). In contrast, an unknown non-Möbius 1,4-dimetallabenzene [Fe(2)(CH)(4)H(4)], also with 8pi electrons, and without phase inversions, has an ASE of -4.1 kcal mol(-1) and a NICS(0)=+15.6, indicative of antiaromaticity. Aromaticity of the proposed Möbius aromatic metallacycles is confirmed by using magnetic (NICS(0), NICS(1)(zz), delta(1)H) and geometric (HOMA) aromaticity criteria, planarity, and near equalized C-C bond lengths, bonding analysis (Wiberg bond indices, NBO, and NLMO analysis). The role of wave function boundary conditions (periodic vs. antiperiodic) in chemistry is further stressed, being equivalent to Zimmerman's concept of nodal parity for Möbius/Hückel systems.

The development of new efficient therapeutics for the treatment of malaria and cancer is an important endeavor. Over the past 15 years, much attention has been paid to the synthesis of dimeric structures, which combine two units of artemisinin, as lead compounds of interest. A wide variety of atemisinin-derived dimers containing different linkers demonstrate improved properties compared to their parent compounds (e.g., circumventing multidrug resistance), making the dimerization concept highly compelling for development of efficient antimalarial and anticancer drugs. The present Perspective highlights recent developments on different types of artemisinin-derived dimers and their structural and functional features. Particular emphasis is put on the respective in vitro and in vivo studies, exploring the role of the length and nature of linkers on the activities of the dimers, and considering the future prospects of the dimerization concept for drug discovery.

Research disclosed since the demonstration of the first examples of primary amine-thiourea organocatalysis in 2006 has shown that primary amine-based thioureas can successfully catalyze a diverse variety of highly enantioselective transformations providing a wide range of versatile organic compounds. Recent remarkable progress with these chiral catalysts is summarized in this review.

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In this review, the recent developments in the field of enantioselective cycloaddition reactions using powerful bifunctional amine-thiourea and amine-squaramide organocatalysts have been described.

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