TADDOLs, which contain two adjacent diarylhydroxymethyl groups in a trans relationship on a 1,3-dioxolane ring, can be prepared from acetals or ketals of tartrate esters by reaction of the latter with aromatic Grignard reagents. They are extraordinarily versatile chiral auxiliaries. Here, a historical review of the subject is followed by discussion of the preparation of TADDOLs and analogous systems, including TADDOLs with N-, P-, O-, and S-heteroatom ligands appropriate for metals. Crystal structure analysis reveals that the heteroatoms on the diarylmethyl groups are almost always in close proximity to each other, joined together by H-bonds, and predisposed to form chelate complexes in which the metallic centers reside in propeller-like chiral environments. Applications of TADDOL derivatives in enantioselective synthesis extend from utilization as stoichiometric chiral reagents or in Lewis acid mediated reactions, to roles in catalytic hydrogenation and stereoregular metathesis polymerization. Derivatives and complexes based on the following metals have so far been investigated: Li, B, Mg, Al, Si, Cu, Zn, Ce, Ti, Zr, Mo, Rh, Ir, Pd, Pt. The number of stereoselective reactions already accomplished with TADDOLs is correspondingly large. It is also easy to prepare TADDOL derivatives that are readily polymerizable and graftable, and to transform them into immobilized solid-phase catalysts. The result is catalysts, simply or dendritically immobilized in polystyrene or on silica gel and characterized by unexpected stability even after multiple use in titanium TADDOLate mediated reactions. TADDOLs show further unusual characteristics that make them useful for applications in material science and supramolecular chemistry: they are the most effective doping agents known for phase transformations of achiral (nematic) into chiral (cholesteric) liquid crystals. The TADDOL OH group that is not involved in intramolecular H-bonding shows a strong tendency to associate intermolecularly with H-bond acceptors. In the process of crystallization this leads, enantioselectively, to the formation of inclusion compounds that lend themselves to the separation of racemic mixtures not otherwise suited to the classical method of crystallization through diastereomeric salts. The high melting points of TADDOLs even make possible the resolution of racemates by distillation! Host-guest compounds formed between TADDOLs and achiral partners can serve as platforms for enantioselective photoreactions. It seems safe to predict that many more applications will be discovered for the TADDOLs and their derivatives. Supporting information for this article is available on the WWW under http://www.angewandte.com or from the author.

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TADDOLs, Their Derivatives, and TADDOL Analogues: Versatile Chiral Auxiliaries

Enamines: recent advances in synthetic, spectroscopic, mechanistic, and stereochemical aspects—I

4.04 – Pyrazoles and their Benzo Derivatives

On the Interaction between Lithium Enolates and Secondary Amines in Solution and in the Crystal



When lithium derivatives generated by lithium diisopropylamide (LDA) are quenched with a D+ source (large excess of ROD), there is frequently only partial deuterium incorporation (non-stoichiometric effect, Scheme 1). Experiments with tert-butyl 2-methylpropionate (1) and its deuterated derivative (2-D)-1 and LDA indicate that the lack of deuteration is not caused by an isotope effect (Scheme 2). A H-bonded complex between the amine (R2NH) and the Li-derivative was envisioned as being responsible for the observed effects. Some crystalline Li-enolate solvates with secondary amines were isolated, and gave rise to only partially deuterated products upon quenching with AcOD/CD3OD (Table 1). Enolates containing the Li-chelating diamine N,N,N′-trimethylethylenediamine (TriMEDA) turned out to be especially suitable for the isolation of single crystals. Thus, two X-ray crystal-structure analyses were undertaken to obtain detailed information about the geometry and bonding in such complexes. The structures of the dimeric N,N-dimethyl-propionamide lithium (Z)-enolate ([2 (Z)-4·2 TriMEDA]; R value 0,049, see Eqn. 2, Figs. 2, 4 and (5) and of the dimeric pinacolone lithium enolate ([2 6·2 TriMEDA]; R value 0,082, see Eqn. 3 and Figs. 3, and 6) were determined. In both centrosymmetric dimeric structures there is a Li-O-Li-O four-membered ring and a H-bridge between TriMEDA and the enolate moiety. In the case of the amide enolate (Z)-4·TriMEDA the bridge points from the amine N-atom to the pyramidalized, enamine-type N-atom of the enolate (N … N distance 3.173(1) A, H … N distance 2.21 (A). In the complex 6·TriMEDA of the ketone enolate there is a H-bridge pointing from the amine N-atom to the enolate double bond (N … Cterminal distance 3.45(1) A, H … Cterminal distance 2.62 A; see Table 3). The geometries of the TriMEDA-Li fragments in the two structures are compared with those of standard TMEDA-Li moieties (Table 2). The two structures are discussed and interpreted using the structure correlation principle; the intermolecular interactions seen in these complexes are considered as points on the reaction coordinates of conversions between the species involved. Thus, they resemble the approach of a secondary amine in the protonation of an enamine N-atom and of an enolate C-atom. At the same time, they represent the final stages of deprotonation of an enammonium ion and of a ketone. The NH … N bridge in 4 is in agreement with experimental observations and with calculations by Muller, indicating that enamines are kinetically protonated on the N-atom. From the pinacolone enolate structures which are now known, (a) possible transition states of deprotonation of carbonyl compounds by Li-amide bases (Figs. 7 and 8), (b) the hypothetical structure of a (i-Pr)2NH/ethyl tert-butyl ketone (E)-enolate (Fig. 8b and Fig. in Footnote 18), c) the approach of the two trigonal centers in an aldol-addition reaction, and the d) trajectory of electrophile attack on a double bond (Fig. 9) are deduced using simple molecular modeling without energy minimization. A comparison with and a discussion of the experimental and theoretical investigations about these same processes by Ireland, Corey, Dauben, Williard, and Houk are given. Finally, we believe that the H-bonding discovered in the crystal structures (Z)-4·TriMEDA and 6·TriMEDA is relevant to what Cram once called the ‘conducted-tour’ mechanism of base-catalyzed racemizations.

Über die Wechselwirkung zwischen Lithium-enolaten und sekundären Aminen in Lösung und im Kristall

TADDOLe, ihre Derivate und Analoga – vielseitige chirale Hilfsstoffe

Plusieurs methodes empiriques sont decrites, permettant d’attribuer sans ambiguite les signaux des protons ou des methyles en 3 et en 5 dans les spectres RMN de pyrazoles N-substitues. Les effets de solvant ont ete particulierement etudies.

Recherches dans la série des azoles: VII — Attribution des signaux RMN de pyrazoles N-substitués

Recherches dans la serie des azoles.

Apres un bref apercu des publications traitant ce sujet, les constantes de couplage du type 3 JHH (Jcis et Jtrans ) presentes dans le cycle pyrazoline-2 sont examinees en relation avec l’atome d’azote sp3 . Pour la premiere fois, est mis en evidence l’effet du doublet p sur une constante de couplage 4 JHH alors qu’aucune des liaisons C — H impliquees n’est en α de l’azote considere.

Robert Jacquier

Papers

Recherches dans la série des azoles: VII — Attribution des signaux RMN de pyrazoles N-substitués

Recherches dans la serie des azoles.

Recherches dans la série des azoles - ΧΧII. Intervention des doublets p des azotes sur Ies constantes de couplage dans Ie cycle pyrazoIine-2

Recherches dans la serie des azoles. Protonation des pyrazolines-2.

Sites de protonation and basicite des enamines tertiaires