A Nonempirical Approach for Direct Determination of the Absolute Configuration of 1,2-Diols and Amino Alcohols Using Mg(II)bisporphyrin

Abstract

We report here a simple, facile, and direct nonempirical protocol for determining the absolute stereochemistry of a variety of chiral 1,2-diols and amino alcohols at room temperature with no chemical derivatization using Mg(II)bisporphyrin as a host. Addition of excess substrates resulted in the formation of a 1:2 host-guest complex in which two substrates bind in an unusual endo-endo fashion because of interligand H-bonding within the bisporphyrin cavity leading to the formation of a unidirectional screw in the bisporphyrin moiety that allowed us an accurate absolute stereochemical determination of the chiral substrate via exciton-coupled circular dichroism (ECCD). The sign of the CD couplet has also been found to be inverted when the stereogenic center is moved by one C atom simply from the bound to an unbound functionality and thus able to discriminate between them successfully. Strong complexation of the alcoholic oxygen with Mg(II)bisporphyrin rigidifies the host-guest complex, which eventually enhances its ability to stereochemically differentiate the asymmetric center. The ECCD sign of a large number of substrates has followed consistent and predictable trends; thus, the system is widely applicable. Moreover, computational calculations clearly support the experimental observations along with the absolute stereochemistry of the chiral substrate.

Exciton‐Coupled Circular Dichroism Characterization of Monotopically Binding Guests in Host−Guest Complexes with a Bis(zinc porphyrin) Tweezer

“…[8,13] Unlike phenylalanine methyl ester G 8 the corresponding amino alcohol G 19 gives a CD signal, however the observed positive Cotton effect for the S-enantiomer is the inverse of the expected one, whereas a negative 1st Cotton effect has been reported for complexes of the S-enantiomer with other bisporphyrin tweezers. [10] That this should be the case in the present study is unlikely as alcohols bind much weaker to zinc as compared to amines. This unexpected result might be caused by the guest binding in a way differing from the literature systems, inducing the opposite helicity of the tweezer.…”

“…For 1 : 1 binding stoichiometry, this leaves only one CD-active option, i. e. the guest placed inside of the bisporphyrin cleft. [10,26] To elucidate the host/guest ratio in the complexes formed with our tweezer we used the "method of continuous variation" (Job plot) for tweezer 1 with D-tyrosine methyl ester D-G 9 (expected to bind 1 : 2 monotopically), and (2S,3R,4R,5R)-1,6diamino-1,6-dideoxy-2,3,4,5-tetra-O-methyl sorbitol [27] (expected to bind 1 : 1 ditopically), Figure 6 and Figure S123 in the Supporting Information. Of their three possible binding motifs ( Figure 5), endo-endo and endoexo might be CD-active.…”

“…This compares favourably with typical ECCD studies, where far higher excess (over 1000-fold) is not unusual. [10,29] The R-enantiomer gives the opposite, a negative Cotton effect. [10,29] The R-enantiomer gives the opposite, a negative Cotton effect.…”

“…The by far most commonly used metalloporphyrin is zinc tetraphenylporphyrin (ZnTPP). [10,11] However, these systems rarely work for molecules with only one available binding site, i. e. ditopic binding of the guest is essential. [9] Although hydroxy and carboxyl groups show considerably weaker binding, guests with these functional groups can be added in huge excess.…”

Chirality sensing of bioactive compounds with amino alcohol unit via circular dichroism

“…3 The chiral amino alcohols are also widely used in peptoid synthesis, 4 and click chemistry to obtain functionalized triazoles. 35,36 The second possibility is the so-called in situ methodology, which uses adequate transition metal complexes as auxiliary chromophores. [6][7][8] This is closely linked to substantially different pharmacological effects, potency at the same receptors, as well as pathways of its metabolic disposition demonstrated by enantiomers.…”