Molecular design strategies that profit from the intrinsic stereoelectronic and electrostatic effects of fluorinated organic molecules have mainly been restricted to bio-organic chemistry. Indeed, many fluorine conformational effects remain academic curiosities with no immediate application. However, the renaissance of organocatalysis offers the possibility to exploit many of these well-described phenomena for molecular preorganization. In this minireview, we highlight examples of catalyst refinement by introduction of an aliphatic C-F bond which functions as a chemically inert steering group for conformational control.

Axially chiral compounds are of significant importance in modern synthetic chemistry and particularly valuable in drug discovery and development. Nonetheless, current approaches for the preparation of pure atropisomers often prove tedious. We demonstrate here a synthetic method that efficiently transfers the stereochemical information of a secondary amine organocatalyst into the axial chirality of tri-ortho-substituted biaryls. An aromatic ring is formed during the dehydration step of the described aldol condensation cascade, leading to highly enantioenriched binaphthyl derivatives. The fundamental course of the reaction is related to the biosynthesis of aromatic polyketides.

Control over redox states and spin multiplicity of photocatalysts throughout a catalytic cycle is crucial for selective and efficient photocatalytic processes. However, the rational design of photocatalysts is often hampered by the mechanistic complexity and low modularity of the catalyst structure. Herein, we demonstrate a photophysical study of diverging photocatalytic pathways that guides the design of organic acridinium catalysts to complement polypyridyl transition metal systems. A combined halogen–metal exchange/directed ortho-metalation provides reagents for a broad range of modular acridinium catalysts with fine-tuned photophysical and photochemical properties such as excited-state lifetimes, redox potentials, and photostabilities poised to refine organocatalytic photoredox methodology.

Structurally well-defined oligomers are fundamental for the functionality of natural molecular systems and key for the design of synthetic counterparts. Herein, we describe a strategy for the efficient synthesis of individual stereoisomers of 1,2-naphthylene oligomers by iterative building block additions and consecutive stereoselective arene-forming aldol condensation reactions. The catalyst-controlled atropoenantioselective and the substrate-controlled atropodiastereoselective aldol condensation reaction provide structurally distinct ter- and quaternaphthalene stereoisomers, which represent configurationally stable analogues of otherwise stereodynamic, helically shaped ortho-phenylenes.

Dedicated to Professor Henri Kagan on the occasion of his 80th birthdayThe structures of iminium salts formed from diarylprolinol or imidazolidinone derivatives and a,bunsaturated aldehydes have been studied by X-ray powder diffraction ( Fig. 1), single-crystal X-ray analyses (Table 1), NMR spectroscopy (Tables 2 and 3, Figs. 2 -7), and DFT calculations (Helv. Chim. Acta 2009Acta , 92, 1, 1225Acta , 2010 Angew. Chem., Int. Ed. 2009, 48, 3065). Almost all iminium salts of this type exist in solution as diastereoisomeric mixtures with (E)-and (Z)-configured þ N¼C bond geometries. In this study, (E)/(Z) ratios ranging from 88 : 12 up to 98 : 2 (Tables 2 and 3) and (E)/(Z) interconversions (Figs. 2 -7) were observed. Furthermore, the relative rates, at which the (E)-and (Z)-isomers are formed from ammonium salts and a,b-unsaturated aldehydes, were found to differ from the (E)/(Z) equilibrium ratio in at least two cases (Figs. 4 and 5, a, and Fig. 6, a); more (Z)-isomer is formed kinetically than corresponding to its equilibrium fraction. Given that the enantiomeric product ratios observed in reactions mediated by organocatalysts of this type are often ! 99 : 1, the (E)-iminium-ion Helvetica Chimica Acta -Vol. 93 (2010) intermediates are proposed to react with nucleophiles faster than the (Z)-isomers (Scheme 5 and Fig. 8).Possible reasons for the higher reactivity of (E)-iminium ions (Figs. 8 and 9) and for the kinetic preference of (Z)-iminium-ion formation are discussed (Scheme 4). The results of related density functional theory (DFT) calculations are also reported (Figs. 10 -13 and Table 4).1. Introduction. -Since the renaissance of organocatalysis 6 ) in 2000 [3], this field has undergone an explosive development 7 ). Of the various types of organocatalysts, compounds with a sec-amino group (proline and its derivatives, including diarylprolinol ethers [5], and amino acid (mostly phenylalanine)-derived imidazolidinones [3b]) have experienced the widest use. They activate a-carbonyl positions for electrophilic attack 8 ) through enamines and b-carbonyl positions for nucleophilic attack through iminium ions, thus opening the door to enantioselectively catalyzed versions of the most important classical synthetic organic reactions 9 ). Entire sequences of such reactions can be performed with one organocatalyst, or with two different species, culminating in the formation of four and more stereogenic centers via so-called domino or cascade reactions [8]. However, much of the mechanistic intricacies of organocatalytic transformations remain unexplored; a casualty of the excitement that the synthetic competence of this class of small molecules has generated. Often reasonable mechanistic models are proposed that are based solely on the stereochemical outcome of the transformation in question.On closer inspection, aspects of many commonly accepted mechanistic models were identified that led to the proposal of possible alternatives. Thus, in proline catalysis, the role of oxazolidinones may not just be part of a parasiti...