Donald J. Cram

Cavitands: Organic Hosts with Enforced Cavities

Organic hosts are now being designed and synthesized which contain enforced cavities large enough to complex and even surround simple inorganic or organic guest compounds.

Host-guest complexation : 43. Synthesis and binding properties of a macrocycle composed of two phenanthrolines and two sulfonamide units

Abstract Treatment of 2,9-bis(chloromethyl)-1,10-phenanthroline with toluenesulfonamide and K 2 CO 3 in HCON(CH 3 ) 2 gave macro-cycle 1 (21%) composed of two phenantroline units bonded to each other through two CH 2 N(Ts)CH 2 bridges. The 18-membered inner ring system contains six nitrogens, each of which is separated by two carbons. A crystal structure of 1.2H 2 O indicated the two faces of the phenanthrolines approach each other to place their four nitrogens nearly in a plane bridged by a water dimer held in position by bifurcated hydrogen bonds. The two ArSO 2 N groups are turned outward, and the hydrogens of their attached CH 2 groups are oriented inward toward the water dimer, which serves as a guest. Complexation was indicated by addition of a variety of salts to a solution of 1 in (CD 3 ) 2 SO, which casued changes in the 1 H NMR by as much as 1.5 ppm. Complexing ions include Li + . Na + , K + , Rb + , Cs + , NH 4 + , Ag + , Cu + , Tl + , Zn 2+ , Cd 2+ , Hg 2+ and Pb 2+ noncomplexing ions are Mg 2+ , Ca 2+ , Sr 2+ , Ba 2+ , UO 2 2+ , and Ce 3+ . A correlation between the chemical shifts of the CH 3 and tolyl aryl protons of the host and the ionic radii of the guests is interpreted in terms of three different host conformations in the various complexes. Equilibrations of the guest cations between 1 and cryptaplexes of Na + , K + , Rb + , Cs + , and NH 4 + picrates in (CD 3 ) 2 SO provided the following estimates of the -ΔG° values of binding of these salts by 1: 8.4, 8.5, 6.8, -1 , respectively.

Chiral recognition in complexation of guests by designed host molecules

ABSTRACT Host molecules have been designed and synthesized to selectively complex and lipophilize guest molecules. Examples of the use of the following binding interactions are given: hydrogen bonding, ion pairing, cation to n-electrons, carbonyl to n-electrons and pi-pi bonding. Multiheteromacrocycles have been prepared whose association constants with tert -butylammonium salts in chloroform range from 6 M -1 . Host molecules with built-in counterions have been prepared that selectively complex and lipophilize metal and alkylammonium cations. Locations of complementary binding sites and non-complementary steric barriers provide for selective binding by host molecules of candidate guest molecules. Locations of appropriate chiral barriers and multiple complexing sites in guest compounds have led to the complete optical resolution of host compounds by optically active amino acids, and of amino acid esters by optically active host compounds. Ratios of association constants for diastereomeric complexes in excess of ten have been obtained. A molecular basis for designing an amino acid resolving machine has been developed.

Rigid cyclophanes that illustrate stereochemical principles

Abstract All of the point groups common to organic chemistry except two are illustrated by known compounds that are rigid [2.2]paracyclophane derivatives. Examples are given of transannular directing effects by acetyl, nitro, and acetoxyl substituents attached to [2.2]paracyclophane. In bromination or chloromethylation, proton loss of a sigma complex is rate-determining, and the oxygens already in the molecule remove the proton being substituted. The synthesis of [2.2.2](1,2,4)cyclophane and [3.2.2](1,2,5)cyclophane, and their unusual chemical properties are described. Transannular hydride shifts out of methyl groups due to proximity effects are reported. Torsional racemizations and epimerizations of [2.2]paracyclophane derivatives are reviewed. The diradical intermediates formed have been intercepted by either H· donors, or by addition to substituted olefins. To account for the stereochemical course of addition and substitution reactions in the side-chains of [2.2]- and [4,2]paracyclophanes, new types of bridged carbonium ions are suggested. Conformational equilibria in the four-carbon side-chain of [4.2]paracyclophane derivatives are discussed.

Concept, structure, and binding in complexation

Structural molecular complexation is central to biological phenomena. Enzymic catalysis and inhibition, immunological response, storage and retrieval of genetic information, replication, biological regulatory function, drug action, and ion transfer all involve structural recognition in complexation. At least one of the partners in most of the complexes of evolutionary chemistry is large and complicated enough to inhibit studies of its detailed structure and an analysis of the forces that control its shape.

Rate-equilibrium correlation for dissociation of a carbon acid

Abstract The rate of racemization of (+)-2-methyl-3-phenylpropionitrile in dimethylsulfoxide-methanol containing sodium methoxide has been correlated with the equilibrium basicity of the medium as measured by the H_function. A log k vs H_plot is linear with a near unit slope over a range of rates which vary by a factor of greater than 106. This strongly supports the previous suggestion by Cram et al.13,14 that the mechanism involves a pre-equilibrium ionization of the carbon acid followed by a rate determining racemization step.

Hemicarcerands with interiors potentially capable of binding large guests

The synthesis and characterization of four new hemicarcerands (1–4) are reported, whose interiors in principle are large enough to embrace such guests as tetraphenylporphyrin or [60]fullerene.

Chiral crown complexes catalyse Michael addition reactions to give adducts in high optical yields

Chiral crowns complexed to potassium bases catalyse with high turnover numbers the Michael additions of a β-ketoester to methyl vinyl ketone, and of two phenylacetic esters to methyl acrylate, to give products of 99–60% optical purity with a configurational bias rationalizable on the basis of steric effects.

Syntheses and binding characteristics of macrocyclic systems containing one to three β-diketone units

One, two, and three β-diketone units have been incorporated into multiheteromacrocycles whose formation constants with metal ions exceed those of an open-chain model by about 1.8 to 6.3 powers of ten.

High chiral recognition in α-amino-acid and -ester complexation

Chiral cyclic polyether hosts containing one 2,2′-substituted-1,1′-binaphthyl and one 2,2′-substituted-3,3′-dimethyl-1,1′-binaphthyl units in CDCl3–CD3CN or CDCl3 have been used to extract from water differentially by factors of up to 52 the enantiomers of eight amino-acids and five amino-ester salts.