The synthesis of optically active calix[4]arenes with one or three substituents on the methylene bridges.

A facile synthesis of optically active mono and trisubstituted calix[4]arenes is described wherein the chirality at the methylene bridges arises from centers of chirality present in the diyne and the bis-carbene complex from which they are constructed.

Optically active calixarenes conduced by methylene substitution.

The first method for the synthesis of optically active calix[4]arenes that are chiral as a result of substitution on the methylene bridges is described. The key step in the synthesis involves the reaction of a biscarbene complex with a diyne, which generates two of the benzene rings and the macrocyclic ring of the calix in a single transformation. The utility of this triple annulation process is demonstrated in the synthesis of di- and tetramethoxycalix[4]arenes. The flexibility of this synthetic approach is demonstrated by the synthesis of two diastereomers of the tetramethoxycalix[4]arenes in which each is synthesized in a stereoselective fashion by proper control of the absolute configurations of the methoxy groups in the biscarbene complex and in the diyne.

A two-directional approach to a (-)-dictyostatin C11-C23 segment: development of a highly diastereoselective, kinetically-controlled Meerwein-Ponndorf-Verley reduction.

A three-step synthesis of a precursor to the C11-C23 segment of (-)-dictyostatin is described. The sequence features a sonication-assisted, enantioselective double hetero Diels-Alder (HDA) reaction catalyzed by Jacobsen's Cr(III) Schiff base catalyst, followed by a novel, highly diastereoselective Meerwein-Ponndorf-Verley (MPV) reduction of the hydropyranone subunits under kinetic control to yield the bis(axial alcohol) 4. Generalized studies of both the HDA and MPV methodologies are also described.

A new convergent strategy for the synthesis of calixarenes via a triple annulation of Fischer carbene complexes.

A new method for the synthesis of unsymmetrical calix[4]arenes is described which involves the reaction of a diyne with a bis-carbene complex of chromium. This synthesis of calixarenes is unique in that it involves the formation of two of the four benzene rings of the calixarene and the macrocyclic ring of the calixarene in the same step. Thus, two of the four benzene rings of the calixarene are identical, but the other two rings may each be different, giving a general method for the synthesis of calixarenes in which there are either two or three differently substituted benzene rings. This protocol gives access to a large family of unsymmetrical calixarenes by the proper choice of arene substitution in the starting diyne and the starting carbene complex. Nine examples are presented in which the yields in the key triple annulation step range from 22 to 41%. The overall yields of calixarenes from commercially available starting materials compare favorably with those from existing methods for the synthesis of unsymmetrical calix[4]arenes.