Mannich and O‐Alkylation Reactions of Tetraalkoxyresorcin[4]arenes – The Use of Some Products in Ligand‐Assisted Reactions

Abstract

The measurement of the pKa of racemic tetramethoxyresorcin[4]arenes explains the failure to obtain good yields in attempted Mannich reactions of these substrates under classical reaction conditions. The failure is related to the lack of adequate concentrations of the iminium ions that results from the reduced acid strength of tetraalkoxyresorcin[4]arenes compared with that of the parent octahydroxyresorcin[4]arenes. However, the preparation of a series of Mannich bases derived from racemic tetraalkoxyresorcin[4]arenes was accomplished under microwave‐assisted aprotic reaction conditions and the use of preformed iminium ion intermediates. When the reactions were carried out with the use of chiral bis(aminol) ethers, mixtures of diastereomers were obtained that could be separated by flash chromatography. The absolute configurations of the enantiomerically pure tetrabenzoxazine derivatives were established in some cases by X‐ray crystallographic analysis and by a comparison of the nuclear magnetic resonance spectroscopic data. The alkylation of racemic tetramethoxyresorcin[4]arenes was achieved with the use of an excess of 2‐bromo‐N‐[(R)‐(+)‐(α‐methylbenzyl)]acetamide in acetonitrile containing potassium carbonate. Enantioselective ligand‐assisted reactions of aromatic aldehydes are also reported with the use of dialkylzinc reagents both in the absence and in the presence of terminal alkynes.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

The Diastereoselective Formation of Tetraalkoxy[4]resorcinarenes Derived from (–)‐(2R)‐2‐Methoxy‐2‐phenylethanol and Proof of Absolute Configurations

“…We have noted previously that diastereoisomeric tetraalkoxyresorcin[4]arenes frequently show different reactivities, especially when sterically demanding alkoxy groups are present. [16,21] To establish the absolute configurations of the diastereoisomers 6a and 6b it was necessary to prepare compounds 11 and 12, with known absolute configurations, by alkylating the enantiomerically pure tetramethoxyresorcin[4]arenes (-)-(M,R)-8 and (+)-(P,S)-8, derived from 3-methoxyphenol and hexanal, which we had prepared and fully characterized previously, and to compare these compounds with those prepared by the methylation of 6a and 6b. [22] We chose to optimize the alkylation of the racemic tetramethoxyresorcin[4]-arene (Ϯ)-8 using the mesylate 9 and tosylate 10 (the enantiomer of which has been reported previously) [23] prepared in 87 and 75 % yields, respectively, from (-)-(2R)-2-methoxy-2-phenylethanol (2), as shown in Scheme 3.…”

“…We also pre-fer to use the term "axial chirality" rather than "cyclochirality" and the configurational symbols (M) and (P) for axially chiral C 4 -symmetric resorcinarenes, [16] as recommended by the Cahn-Ingold-Prelog system. [19] The configurational symbol (M) refers to an anticlockwise sequence of groups around the chiral axis as defined by the Cahn-Ingold-Prelog system and the configurational symbol (P) to a clockwise sequence; in each case, the sequence is determined either by viewing the groups from inside the cavity of the resorcin[4]arene or from above the upper polar rim; both operations give the same configurational symbol.…”

“…HRMS: Calcd. for C 16 First Method: Tetramethoxyresorcinarene (-)-8 (100 mg, 0.1 mmol, 1 equiv. ), (2R)-2-methoxy-2-phenylethyl toluenesulfonate (10; 310 mg, 1.0 mmol, 10 equiv.)…”

“…[15] We also recently reported the conversion of a number of racemic tetraalkoxyresorcinarenes into diastereoisomeric mixtures of tetrakis(1,3-benzoxazine) derivatives, together with the separation of the diastereoisomers and proof of their absolute configurations. [16] …”

C 4 Dissymmetric resorcinarene derivatives: synthesis, crystal structure and micelle formation

“…The tetraethyl ester (2) was prepared according to the previously published method [19], by the reaction of 1 [20] (Scheme 1) with ethyl bromoacetate and anhydrous potassium carbonate. All spectroscopic data matched the published values [19].…”