A facile enantioselective synthesis of chiral pyrazolidines via a [3+2] cycloaddition reaction, involving a BINOL-derived phosphoric acid and an in situ generated BINOL phosphate-derived silicon Lewis acid, which may act cooperatively, has been developed.

In recent years, binaphthyl compounds have found frequent applications in the design of various asymmetric organocatalysts, because binaphthyl structures are an attractive platform for organocatalyst development, particularly in light of their axial chirality characteristic. In this review, we discuss recent achievements in developing enantioselective transformations by using catalysts derived from axially chiral binaphthyls: Brønsted acids (different from BINOL-phosphates), Lewis acids, and hydrogen-bond donors. Results published after 2004 through 2010 are presented.

A first and fairly mild metal-free catalytic route was developed for the [3+2] cycloadditions of different N-acylhydrazones to cyclopentadiene, providing the synthetically andbiologically important five-membered cyclic compounds pyrazolidines. The reaction was successfully conducted in high yields (up to 99 %) with high diastereoselectivities (up to 98:2 dr) by using catalytic amounts of TMSOTf (trimethylsilyl triflate) as a readily available Lewis acidic catalyst. The experimental findings were supported by DFT calculations of the reaction mechanism. The theoretical and experimental diastereomeric excess values show good agreement, rendering the computations an efficient tool for predicting the selectivities in these and related reactions.

Versatile synthetic intermediates—α,β-epoxyketones and α,β-epoxyaldehydes—can be obtained through asymmetric organocatalytic epoxidation of α,β-unsaturated ketones and aldehydes. This Review focuses on some recent advances in these epoxidation reactions with respect to scope and limitations with polyamino acids, phase-transfer catalysts (PTCs), amines, and guanidines as chiral organocatalysts. Furthermore, recent results obtained with chiral peroxides are discussed. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.201000006

Möbius aromaticity, predicted by Edgar Heilbronner in 1964, is a stabilizing effect exhibited by 4 n 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 δ-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 4 n π aromatic planar metallacyclic examples and their building principles. Aromatic stabilization energy (ASE) of a 8 π metalla-cycloheptatriene [Fe(CH)₆H₂], with four doubly occupied π 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 [Fe₂(CH)₄H₄], also with 8 π 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, δ¹H) and geometric (HOMA) aromaticity criteria, planarity, and near equalized CC 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.

Deracemisation of racemic or scalemic conglomerates of intrinsically chiral compounds appears to be a promising method of chiral resolution. By combining the established methods of asymmetric synthesis and the physical process of crystal growth, we were able to achieve a complete deracemisation (with 100 % ee) of an asymmetric Mannich product conglomerate—vigorously stirred in its saturated solution—from a starting enantiomeric excess value of 15.8 % in the presence of pyrrolidine (8 mol %) as an achiral catalyst for the CC bond-forming reaction. Strong activation of this deracemisation process was observed on mild isothermal heating to only 40 °C, resulting in dramatic acceleration by a factor of about 20 with respect to the results obtained at room temperature. Despite the fact that the racemisation half-life time of the nearly enantiopure Mannich product (with 99 % ee) in the homogenous solution at the reaction temperature is eight days, the deracemisation process took only hours in a small-scale experiment. This apparent paradox is explained by a proposed rapid enantiomerisation at the crystal/solution interface, which was corroborated by a ¹³C labelling experiment that confirmed the involvement of rapid enantiomerisation. Frequent monitoring of the solution-phase ee of the slowly racemising compound further revealed that the minor enantiomer dominated in solution, supporting an explanation based on a kinetic model. A generalisation of the process of “aymmetric autocatalysis” (resulting in automultiplication of chiral products in homogenous media) to encompass heterogeneous systems is also suggested.

Amino- and methyl-disubstituted derivatives of an aromatic 12π electron pyrrole homologue Möbius 1H-aza[11]annulene are predicted computationally at the B3LYP/6-31G* level of theory to be distinctly aromatic and a neutral ground state on its potential surface. The parent annulene has a nonaromatic conformation, which is 6.0 kcal mol^–1 lower in energy at the CCSD(T)/D95*//B3LYP/6-31G* level of theory than a structurally very similar Möbius conformation. After derivatization, however, geometry optimizations of the two lowest-energy – Möbius and non-Möbius – heteroannulene conformations both converged two a single Möbius minimum, whereas two (Möbius and non-Möbius) distinct difluoro- substituted species could be located 1.8 kcal mol^–1 apart in energy at the B3LYP level. The Möbius minimum is 7.5 kcal mol^–1 lower in energy at the coupled cluster level than a “Hückel topology” form derived from a known bridged 1H-[4,9]methano[11]annulene. Several possible reactive modes are investigated in order to assess the relative stability of the Möbius parent annulene. In addition, we report formal novel examples for charged and neutral Möbius triplet aromatic annulenic and heteroannulenic systems, some of which also exhibit distinct aromatic properties. Further fundamental insights into the phenomenon of “Möbius aromaticity” are suggested. The aromaticity of Möbius annulenes is for the first time linked to wavefunction boundary conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Asymmetric synthesis aims at obtaining enantio-enriched products in stereoselective reactions under a chiral influence. We demonstrate both mathematically and numerically that, even under nominally achiral conditions, fully homochiral steady states can be obtained in open reactive systems by spontaneous mirror-symmetry breaking in the homogenous solution phase when the autocatalytic reaction network is closed in the form of coherently coupled antagonistic reversible reaction cycles which, paradoxically, allow for complete recycling of the reactant. We show that the fully reversible Frank mechanism for spontaneous mirror-symmetry breaking is closely related to the Lotka–Volterra system, which models predator–prey relations in ecosystems. Amplification of total enantiomeric excess and the principle of microscopic reversibility are not in conflict for all conceivable reactions. A viable and widely applicable reaction protocol is introduced and discussed, and it permits the theoretical implications to be applied to practical laboratory examples. Implications for the possible origin of biological homochirality on early earth are discussed.