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Four new diphosphane ligands, (R)-4, (R)-5, (S)-6, and (R)-7 (Schemes 3, 4, 6, and 7), featuring metalcoordination sites located in the major groove of chiral 1,1'-binaphthalene clefts, were prepared in enantiomerically pure form. The performance of this new class of ligands was tested in enantioselective, Pd-catalyzed allylic alkylation reactions with acyclic and cyclic methyl carbonates 28 – 30 as substrates under various reaction conditions (Schemes 8 and 9). Using sodium phenyl sulfinate as a nucleophile, the reactivity of the catalysts formed with the new ligands and suitable palladium precursors was found satisfactory (>90%); however, the ee values were in all cases poor (<4%). Slightly better results were obtained using anions of dimethyl malonate as nucleophiles, but, also in these cases, the ee values never exceeded 17% (Table). ³¹P-NMR-Spectroscopic investigations revealed the formation of multiple-catalyst species in solution (Fig. 2), and molecular modeling suggested a lack of embedding of the coordinated substrate in a `chiral pocket' (Fig. 3), which probably accounts for the observed low level of enantioselectvity.

The optically active allosteric receptors (−)-(R,R)-3 and (+)-(R,R)-4 were synthesized for the molecular recognition of the N-(benzyloxy)carbonyl (N-Cbz)-protected excitatory amino acids aspartic acid (Asp, 1) and glutamic acid (Glu, 2). These macrocyclic structures consist of two 1,1'-binaphthalene moieties connected by two but-2-yne-1,4-diyl (for (−)-(R,R)-3) or p-xylylene (for (+)-(R,R)-4) bridges between the O-atoms in the minor grooves. Each 1,1'-binaphthalene moiety contains two 2-acetamidopyridin-6-yl (CONH(py)) H-bonding sites in the major groove to bind excitatory amino-acid derivatives via two COOH█bk█···█ek█CONH(py) H-bonding arrays and additional secondary electrostatic interactions. The formation of stable complexes with 1 : 2 host-guest stoichiometry was proven by the evaluation of fluorescence binding titrations using a multiple-wavelength nonlinear least-squares curve-fitting procedure, Job plot analysis, and solubilization experiments. Complexation of the first excitatory amino-acid guest at binding site 1 reduces the affinity for the second guest at binding site 2. As measures for the negative cooperativity between the two sites, the ratios of the association constants for the first and second binding events, {Ka(1 : 1)/Ka(1 : 2)}corr. (corrected for the statistical preference of the 1 : 1 complex formation), were found to adopt values between 1.4 and 2.4, and the Hill coefficients nH varied between 0.49 and 0.59.

A series of optically active 1,1′-binaphthalene-derived receptors with N-(pyridine-2,6-diyl)acetamide [CONH(py)] H-bonding sites in the 6,6′-positions has been prepared for the enantioselective complexation of the N-carbobenzyloxy (Cbz)-protected excitatory amino acids aspartic (Asp) and glutamic (Glu) acid via two COOH  · 4;· 4;·  CONH(py) H-bonding arrays and additional secondary bonding interactions. The conformational homogeneity of the receptors is enhanced by locking the dihedral angle θ about the chirality axis through the C(1)–C(1′) bond of the 1,1′-binaphthalene moiety either by bridging the 2,2′-positions or by attaching bulky substituents to these centres. Computer modelling has shown that bridging is more efficient in locking this dihedral angle than the introduction of bulky substituents, and these predictions have been confirmed by 1H NMR binding studies in CDCl3 and in CDCl3–CD3OD 99.8∶0.2. Plots of the enantioselectivity Δ(ΔG °) (difference in stability between diastereoisomeric complexes) in the recognition by the bridged receptors as a function of the enforced dihedral angle θ are peak-shaped, and the highest values have been measured in CDCl3 (300 K) for the complexation of the enantiomers of N-Cbz-Asp [Δ(ΔG °) 4;= 4;6.9 kJ mol–1] and N-Cbz-Glu [Δ(ΔG °) 4;= 4;5.2 kJ mol–1] by (R)-21 (θ 4;= 4;86 4;± 4;4°). The more stable diastereoisomeric complexes are highly structured, and tight host–guest bonding has been confirmed by the observation of up to five intermolecular NOEs. Enforcing the conformational homogeneity by bridging represents a new general principle for improving the chiral recognition potential of 1,1′-binaphthalene receptors.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.