3R scheme

Of the diverse supramolecule architectures considered for chemosensor design, we emphasize one—a miniature bucket. Supramolecular buckets maintain a cylindrical cavity with structurally and chemically well-defined upper and lower rims. By virtue of its molecular shape, the bucket is an intrinsic receptor site. A supramolecular bucket alone, however, is an inadequate chemosensor because a signal cannot be produced. In the simplest chemosensing constructs, the analyte generates a signal upon association with the bucket whereas in more elaborate designs, functionality at the rim of the bucket offers sites to attach a discrete reporter site. The thematic focus of this chapter is bucket chemosensors that operate by the 3R scheme shown in Fig. 2, namely, a measurable change in a... 

Figure 2 The 3R scheme that is the focus of this chapter. The supramolecule is a bucket receptor site, which can be filled with analyte A. Recognition of analyte produces...

Many of the optodes referred to here employ sensors operating on the basis of the 3R scheme (see Section 13.1), the relay mechanism being photoinduced electron transfer, PET. Due to their applicability in various chemical and biological processes, they have received much attention in recent years [1, 7, 8, 10]. Of note in this context are sensors that become fluorescent upon complexation of an analyte because the binding of the analyte within the sensor prevents the PET that suppresses fluoresence in the absence of the analyte [38]. Anthryl aza-crown-ca-lix[4]arene, a iC-selective sensor (see Chart 13.4), exhibits such behavior. It selectively binds potassium ions, and this triggers a substantial increase in anthryl fluorescence through disruption of the PET quenching process [9, 39]. 

S,3R)-Aziridine-2-carboxylic amide 258 (Scheme 3.95) has been used in the synthesis of the cyclic guanidino amino acid, L-epicapreomycidine (260) [145]. Treatment of 258 with saturated ammonia in methanol at 30 °C for 4 days in a pressure bottle resulted in the aziridine ring-opening product, which afforded 259 in 52 % yield after removal of the Cbz protecting group. 

An interesting example of regioselective CM with ethylene as a tool in natural product degradation was recently disclosed by Hawaiian authors [149]. Thus, CM using catalyst C and ethylene gas was used to degrade the plant polyacetylene oxylipin (+)-falcarindiol (342) with uncertain stereochemistry at C3. As the reaction provided a meso product (343) in 81% yield by regioselective attack at the aliphatic side chain, the natural compound 342, isolated from a Hawaiian endemic plant, had the 3R,8S configuration shown in Scheme 66. 

A microwave-assisted variant of the Rosenmund von Braun reaction has also been developed (Scheme 73) [83]. DMF at 200 °C proved not very useful for the cyanodehalogenation of methyl (3R)-6-bromo-5-oxo-2,3-dihydro-5ff-[l,3]thiazolo[3,2-a]pyridine-3-carboxylates since only low yields of the corresponding nitrile were obtained, and there were substantial amoimts of unconverted starting material. Extending the reaction time from 10 to 20 min gave more desired reaction product but also significant amoimts of... 

However, upon dissolution, an epimerization of the anions can occur in the presence of acidic counter-ions. This is particularly true for 16a-16d [39]. The nature of the solvent (MeOH, CHCI3) plays a crucial role on the kinetics of epimerization and the position of the resulting equilibrium. For anions made with a 2R, 3R) tartaric backbone, a A configuration is always preferred in MeOH the selectivity, obtained after a slow equilibration, being independent of the nature of the ester alkyl chain (diastereomeric ratio (d.r.) 3 1). However, in chloroform, the A diastereomer is rapidly obtained and the selectivity is best if the ester side chain is sterically demanding (d.r. 2 1 to 9 1 from 16a to 16d) (Scheme 16). 

In addition to the enzymatic hydrolysis of esters, there also ample examples where an epoxide has been cleaved using a biocatalyst. As described by the Faber group [19], reaction of the ( )-2,3-disubstituted ds-chloroalkyl epoxide roc-8-40 with a bacterial epoxide hydrolase (BEH), led to the formation of vie-diol (2 ,3S)-8-41 (Scheme 8.11). The latter underwent a spontaneous cydization to give the desired product (2i ,3i )-8-42 in 92 % ee and 76 % yield. The same strategy was used with the homologous molecule rac-8-43, which afforded the THF derivative (2R,3R)-S-4S in 86% ee and 79% yield. 

Scheme 10.13).110 New alkaloids from ants, (3R, 5.S, 9fl)-3-butyl-5-(l-oxopropyl)indolizidine and (3R, 5R, 9/ )-3-butyl-5-(l-oxopropyl)indolizidine, are identified and synthesized as outlined in Scheme 10.14.111... 

Hemiacetal 25 [(3 ,4S,l E)-3,4-bis(r-butenyl)tetrahydro-2-furanol] is the male pheromone of the spined citrus bug (Biprorulus bibax). Scheme 38 summarizes Mori s synthesis of 25 [61]. Claisen rearrangement (A B) and lipase-catalyzed asymmetric acetylation [meso-C >(5S,6R)-D] were the two key steps of the synthesis. Further purification of D was executed at the stage of its crystalline derivative E. In this particular case, the unnatural (3S,4R,l E)-25 was as active as the natural (3R,4S,VE)-25. Accordingly, a more efficient synthesis of ( )-25 was achieved by the rearrangement of F, avoiding the use of toxic HMPA [62]. 

Scheme 60 shows Oppolzer s synthesis of (2S,3R,rS,2 S)-serricorole (42), the female-produced sex pheromone components of the cigarette beetle (Lasio-... 

The field response of the European pine sawfly, Neodiprion sertifer, to the acetate of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol 1 and the effect of the (2S,3R,7R)-iso-mer was studied from Japan in the east to Canada in the west. The addition of the (2S,3R,7R)-isomer was benign in Japan, inhibitory in Europe with the inclusion of as little as 1%, and its presence essential in Siberia. These findings will allow for the development of a more efficient N. sertifer monitoring scheme without having to determine the stereochemistry produced in each population [27]. 

Combinatorial solution-phase cycloadditions of (1Z,4R, 5R )-4-benzoylamino-5-phenylpyrazolidin-3-on-l-azomethine imines 320 to 3-keto esters afforded a library of 26 highly pure bicyclic pyrazolidinones 713 in 6-89% yields and in 14-100% de. Most of the products were isolated as mixtures of the major (13, 23, 3/ , 5/ , 6/ )-epimers 713 and the minor (1R, 2A, 3R, 5R, 6R )-epimers 714 (Scheme 113). Epimerization of these cycloadducts at the anomeric position in solution was confirmed by H NMR spectroscopy <2007MI717>. 

Addition of A-mesityl benzimidazolyl carbene 720 to an a,/3-unsaturated aldehyde generates a homoenolate intermediate that undergoes an addition/acylation sequence with azomethine imine 719 to afford (3R, 5S, 6S )-177-pyrazolo[l,2- ]pyridazine-l,8(5//)-diones 721 with excellent diastereoselectivity. Compound 721 (Ar = R = Ph) treated with sodium hydoxide in methanol or benzylamine provided nearly quantitatively, ring-opened products 722a and 722b, respectively (Scheme 116) <2007JA5334>. 

Scheme 26 Synthesis of (3R,5 )-2,6-dimethyl-2,3-epoxy-octa-5,7-diene, isolated from male Amblypelta nitida [121]...

The chiral A/ -propionyl-2-oxazolidones (32 and 38) are also useful chiral auxiliaries in the enantioselective a-alkylation of carbonyl compounds, and it is interesting to observe that the sense of chirality transfer in the lithium enolate alkylation is opposite to that observed in the aldol condensation with boron enolates. Thus, whereas the lithium enolate of 37 (see Scheme 9.13) reacts with benzyl bromide to give predominantly the (2/ )-isomer 43a (ratio 43a 43b = 99.2 0.8), the dibutylboron enolate reacts with benzaldehyde to give the (3R, 25) aldol 44a (ratio 44a 44b = 99.7 0.3). The resultant (2R) and (25)-3-phenylpropionic acid derivatives obtained from the hydrolysis of the corresponding oxazolidinones indicated the compounds to be optically pure substances. 

The same soluble MPEG-resin was used for the immobihzation of (3R,4R)-3,4-bis(diphenylphosphino)-pyrrolidine ligand (56) (Scheme 4.34). The rhodium(I) catalyst was generated in situ from ligand (56) and [Rh(COD)2] BF4 and was found to be active in the asymmetric hydrogenation of prochiral enamides [126]. 

Moreover, phosphoric acid (5)-3r (5 mol%, R = SiPhj) bearing a bulky triphe-nylsilyl group turned out to be a suitable catalyst for the asymmetric Friedel-Crafts alkylation of iV-alkyl pyrroles 31 with M-benzoyl-protected aldimines 32 (Scheme 12) [23]. 2-Pyrrolyl amines 33 were obtained in high yields (66-97%) and moderate to high enantioselectivities (42 to >99% ee). 

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