Synthesis of Phototrappable Shape-Shifting Molecules for Adaptive Guest Binding

Abstract

We have designed and synthesized oligosubstituted bullvalenes 1 and 2 as adaptive molecules that can change their shapes in order to bind tightly to a suitable guest. By incorporation of a photolabile o-nitroveratryloxycarbonate (NVOC) group into bullvalenes 1 and 2, tightly binding species can be selectively isolated from a population of hundreds of interconverting structural isomers. Spontaneous strain-assisted Cope rearrangements allow these shape-shifting molecules to exist in a dynamic equilibrium of configurationally distinct valence isomers, as revealed by dynamic NMR and HPLC studies. When NVOC bullvalenes 1 and 2 were exposed to UV light, the cleavage of the NVOC group resulted in a mixture of static isomers of the corresponding bullvalone. Binding studies of NVOC bisporphyrin bullvalene 1 demonstrated that the dynamic isomeric equilibrium shifted in the presence of C(60), favoring configurations with more favorable binding affinities. Irradiation of a mixture of 1 and C(60) with UV light and isolation of the major static isomer yielded an isomer of bisporphyrin bullvalone with a binding affinity for C(60) that was ∼2 times larger than that of the nonadapted isomer bisporphyrin bullvalone 41.

Racemization as a stereochemical measure of dynamics and robustness in shape-shifting organic molecules

“…4C). The remainder of the HPLC trace was characterized by a complex set of peaks of similar profile to a prior study from our group on the chromatographic analysis of oligosubstituted bullvalenes (25). Four dynamic bullvalene fractions (b-e) were collected from the HPLC separation and individually analyzed by CD spectroscopy and analytical HPLC (Fig.…”

“…1). We have recently developed a rational synthesis of oligosubstituted bullvalenes that allows for the incorporation of diverse pendant groups (23)(24)(25). NMR and HPLC investigations supported our assertion that these molecules are dynamic but did not ascertain if the structures are true shapeshifting molecules that freely rearrange their pendant groups or merely oscillate between a few discrete states without accessing the many other theoretically possible structural isomers.…”

Synthesis of Barbaralones and Bullvalenes Made Easy by Gold Catalysis

“…[1,2] These molecules undergo low energy [3.3]-sigmatropic rearrangements,w hich in the case of bullvalene lead to 1209 600 degenerate tautomers, [3][4][5] whereas al ower number of constitutional isomers are possible for substituted bullvalenes [6][7][8] and only two exist for barbaralone (1a).[9]Syntheses of these fluxional molecules requires multistep procedures that proceed with low overall yield, often using explosive and toxic diazomethane.T hus,t he optimized synthesis of barbaralone (1a), en route to bullvalene (3a), [10] starts with the Büchner reaction of ethyl diazoacetate with benzene to form 4, [11,12] which is converted into 1a in four steps via diazomethyl ketone 5 (Scheme 1).[10] Bullvalene (3a)can be prepared from 1a in four additional steps by two different procedures by homologation of 1a to bullvalone (2a)w ith diazomethane. [2,10] Barbaralone (1a)h as also been prepared from (cyclooctatetraene)tricarbonyliron in two steps in approximately 36 %yield.…”

“…[2,10] Barbaralone (1a)h as also been prepared from (cyclooctatetraene)tricarbonyliron in two steps in approximately 36 %yield. [13] 1-Methylbarbaralone (1w)w as prepared by ap rocedure similar to that shown in Scheme 1using ethyldiazomethane in the reaction with cycloheptatriene carbamoyl chloride to form the homologue of 5.[9b] Although some ingenious syntheses of highly substituted bullvalenes have been designed, [8] most bullvalenes have been prepared from parent 3a.T hus,f or example,p henylbullvalene (3b)w as obtained in three steps (26 %y ield) from 3a by dibromination, dehydrobromination with KOtBu, and reaction of the resulting bromobullvalene with Ph 2 CuLi.[7d]Current synthetic art does not allow preparation of substituted barbaralones in ag eneral way, [14] which limits the access to fluxional homologues and other theoretically interesting molecules. [12,15] We have recently found that 7-aryl-1,3,5-cycloheptatrienes undergo ag old(I)-catalyzed retro-Büchner reaction to form highly reactive aryl gold(I) carbenes (a decarbenation reaction).…”

“…[1,2] These molecules undergo low energy [3.3]-sigmatropic rearrangements,w hich in the case of bullvalene lead to 1209 600 degenerate tautomers, [3][4][5] whereas al ower number of constitutional isomers are possible for substituted bullvalenes [6][7][8] and only two exist for barbaralone (1a).…”