Pyrrole derivatives, asymmetric

Asymmetric synthesis of ft-amino acids with participation of oxazolidine, furan, and pyrrole derivatives 02MI53. 

For regioselective introduction of a chiral sidechain to C-2 of the indole nucleus the higher nucleophilicity of C-3 must be overcome. Employing the 4,7-dihydro derivatives the preferred reaction site is moved (to the active a-position of 4,5-disubstituted pyrroles), and asymmetric Michael reaction has been demonstrated with a chiral 3,3 -dibromo-BINOL as catalyst. ... 

All this information about the reactivity of pyrrole and its derivatives as dienes for Diels-Alder reactions was obtained from the values computed on two separated reactants. It is much more appropriate to compare changes of the FMO energies for reactants to reach transition state structures. Some representative transition state structures for acetylene addition to pyrrole derivatives are presented in Figure 3. The transition state structures are for synchronous formation of both CC bonds with slightly asymmetric transition state structures, although both diene and dienophiles have a plane of symmetry that coincides with a plane of symmetry for the transition state structure. All of these transition state structures have similar bond distances for CC bonds, which is true for almost all Diels-Alder reactions. The FMO orbital changes for transformation of reactants into transition state structures are presented in Table 16. 

Modification of the core motif allows for 2,5-diamido-pyrrole derivatives, 99, having a additional NH hydrogen-bond donor compared with isophthalamide receptors. A binding constant of 2500 M for benzoate in acetonitrile is observed with an asymmetric binding mode apparent in the molecular structure measured by X-ray crystallography. 

Other recent examples of inverse electron-demand Diels-Alder reactions in water are the cycloadditions of ( )-3-diazenylbut-2-enes 72 with a variety of vinyl ethers. The results of cycloaddition of 72 with ethyl vinyl ether (61) are reported in Table 5.5. The reactions were always faster in heterogeneous aqueous medium than in organic solvent and the endo adduct was the prevalent reaction product. Pyrrole derivatives such as ethyl-2-methyl-1-ureido-lH-pyrrole-3-carboxylates, derived from zwitterionic [3 + 2] cycloaddition reactions, were sometimes observed and a reaction mechanism of their formation has been proposed. In water, as well as in DCM, 72 (R = OEt, Ri = H) behaves like an electron-acceptor heterodiene even with a highly reactive diene such as cyclopentadiene, giving quickly, at 15°C, only the endo adduct. The cycloaddition of 72 (R = OEt, Ri = H) with the chiral vinyl ether (-F)-2-(ethenyloxy)-3,7,7-trimethylbicyclo[4.1.0]heptane (62x) was complete in water in 68 h at 15°C and gave a mixture of 83 17 endo/exo adducts with modest enantioselectivity. This is the first example of an asymmetric inverse electron-demand Diels-Alder reaction performed... 

The catalytic asymmetric 8 + 2-cycioaddition of azaheptafulvenes with alkyiidene malonates formed functionaiized cycioheptatriene-fused pyrrole derivatives with exceiient yieids (up to 99%) and diastereoseiectivities (>99 5 dr) and enantioseiectivities (91-97% ee) The SnC -catalysed 8 + 3-cycloaddition reaction of substituted tro-pones (150) with donor-acceptor aminocyciopropanes (151) lead to amino-substituted tetrahydrocyclohepta[fc]pyrans (152) with complete regio- and diastereo-selectivity (Scheme 45). 

Aromatic nucleophiles In the first reports on organocatalyzed asymmetric F-C reactions, indole and pyrrole derivatives were mainly used. Indeed, apart their aptitude in undergoing electrophilic substitutions, the indole derivatives... 

Carbery DR, Donohue TJ. Enantiopure oxazoUdinones as chiral acids in the asymmetric protonation of iV-Boc pyrrole derived enolates. Chem. Commun. 2004 722—723. 

Remote asymmetric induction using chiral sulfoxides, derivatives of furan, thiophene, and pyrrole 98YGK798. 

In order to prepare asymmetric meso-porphyrinylsugar derivatives (mono-, di- and tri-glycosylarylporphyrins), pyrrole was condensed with a mixture of glycosylated and nonglycosylated aldehydes.17,21,24,44 46 Several porphyrinylsugar derivatives were prepared by this synthetic methodology. The saccharide unit can be directly linked to the porphyrin macrocycle 35-50 or separated from the phenyl group by a spacer, such as in the case of derivative 51-53 shown below (Fig. 4). 

Arai and coworkers197 reported the utilization of a chiral pyrrole sulfoxide as a chiral auxiliary in the asymmetric Diels-Alder reactions of its /V-cinnamoyl and /V-crotonyl derivatives 313 with cyclopentadiene which gave 314-317 (equation 87). The results have been summarized in Table 18. The yield as well as the endo/exo selectivity and the de proved to depend on the type and amount of Lewis acid used. 

In particular the synthetic approach to dihydrofurans (first equation in Figure 4.23) represents a useful alternative to other syntheses of these valuable intermediates, and has been used for the preparation of substituted pyrroles [1417], aflatoxin derivatives [1418], and other natural products [1419]. The reaction of vinylcarbene complexes with dienes can lead to the formation of cycloheptadienes by a formal [3 + 4] cycloaddition [1367] (Entries 9-12, Table 4.25). High asymmetric induction (up to 98% ee [1420]) can be attained using enantiomerically pure rhodium(II) carboxylates as catalysts. This observation suggests the reaction to proceed via divinylcyclopropanes, which undergo (concerted) Cope rearrangement to yield cycloheptadienes. 

Figure 6.17 Pyrrole thiourea derivatives evaluated for catalytic activity and selectivity in the asymmetric acetyl-Pictet-Spengler reaction.

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