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

• Published in: Angewandte Chemie International Edition Vol. 40; no. 1; pp. 92 - 138
• Main Authors: Seebach, Dieter, Beck, Albert K., Heckel, Alexander
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 05.01.2001; WILEY‐VCH Verlag GmbH
• Subjects: asymmetric catalysis; asymmetric synthesis; enantiomer separation; TADDOLs
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/1521-3773(20010105)40:1<92::AID-ANIE92>3.0.CO;2-K

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. Since their discovery nearly 20 years ago TADDOLs and their derivatives have revealed themselves to be true chiral auxiliary systems. Compounds of this type are accessible from tartaric acid with an almost unlimited degree of structural variety. They serve not only as homogeneous and solid phase bound chiral reagents and ligands for stoichiometric and catalytic applications, but also assist in creating cholesteric phases and host lattices capable of distinguishing between enantiomeric inclusions or facilitating enantioselective solid‐phase reactions. The availability of over 120 crystal structures (see the overlays in the picture) makes it possible to discuss mechanistic models for courses of the various reactions.