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The synthesis and characterization of copper(I) complexes of the novel pyridine-containing macrocyclic ligand (PC-L) and their use as catalysts in the Henry reaction are reported. The pyridine-based 12-membered tetraaza macrocyclic (PC-L) ligand 1 can be obtained in good overall yield (85%) from commercially available starting materials. The Cu(I) complexes showed good catalytic activities in the Henry reaction of different aldehydes and nitroalkanes. Remarkable diastereoselectivity was observed when isatine was reacted with nitroethane under catalytic conditions. Copyright © 2011 John Wiley & Sons, Ltd.

We have developed a three-component, one-pot domino reaction that combines the allylindation of 1H-indole-3-carbaldehyde with the dehydrative alkylation of stabilized Cnucleophiles (e.g., electron-rich heteroarenes, electron-rich aromatics, and stabilized enols) or N nucleophiles (e.g., azoles). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Four new ligands for lanthanide ions based on the H3do3a (=1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid) structure and bearing one N-sulfonylacetamide arm were synthesized, i.e., H4dota-NHSO2R=10-{2-[(R)sulfonylamino]-2-oxoethyl}-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acids 1a–e. A 15N-NMR study of the 15N-labelled Eu3+ complex of one such ligands, 1d, showed that the coordination of the N-sulfonylacetamide arm involves the carbonyl O-atom rather than the N-atom. The relaxometric properties of the corresponding Gd3+ complexes were investigated as a function of pH and temperature. These complexes have relaxivities in the range 4.5–5.3 mM−1 s−1, at 20 MHz and 25°, and are characterized by a single H2O molecule in their inner coordination sphere. The mean residence lifetime of this molecule is relatively long (500–700 ns) compared to other anionic complexes. The slow rate of H2O exchange can be justified by the extensive delocalization of the negative charge on the N-sulfonylacetamide arm. The long residence time of the coordinated H2O allowed the observation of the effect of the prototropic exchange on the relaxivity. The study of the interaction between the complex [Gd(1e)]- and HSA revealed a weak affinity constant highlighting the importance of a localized negative charge on the complex to promote a strong interaction with the protein.

The three novel pyridine-containing 12-membered macrocyclic ligands 1–3 were synthesized. The coordinating arms are represented by three acetate moieties in 1 and 3 and by one acetate and two phosphonate moieties in 2. In all three ligands, the acetate arm in the distal position is substituted, with a benzyl group in 1 and 2 and with an arylmethyl moiety in 3. The relaxivities r1p (20 MHz, 25°) of GdIII complexes are: GD⋅1, r1p=8.3 mM−1 s−1; GD⋅2, r1p8.1 mM−1 s−1; Gd⋅3, r1p10.5 mM−1 s−1. 1H-NMRD and 17O-NMR T2 data show that Gd⋅1 and Gd⋅3 contain two H2O molecules in the inner sphere, whereas the presence of two phosphonate arms allows the coordination of only one H2O molecule in Gd⋅2. Interestingly, the exchange lifetime of coordinated H2O in the three complexes is similar in spite of the difference in the coordination number of the GdIII ion (i.e., 9 in Gd⋅1 and Gd⋅3, and 8 in Gd⋅2). 1H-Relaxometric measurements at different pH and in the presence of lactate and oxalate were carried out to get some insight into the formation of ternary complexes from Gd⋅1 and Gd⋅3. Finally, it was found that binding to human-serum albumin (HSA) of Gd⋅1 and Gd⋅2, though weak, yields limited relaxivity enhancements, likely as a consequence of effects on the hydration sphere caused by donor atoms on the surface of the protein.

The formation of a macromolecular adduct between a suitably functionalized GdIII complex and an exogeneous substance such as a poly-β-cyclodextrin (see picture) forms the basis of the novel route to contrast agents for magnetic resonance imaging endowed with high relaxivity discussed herein.

The present review is devoted to illustrate the state of the art of the syntheses of indoles, focusing particularly on the most recent developments of new synthetic approaches. Emphasis is given to the preparation of natural products or bioactive compounds containing the indole unit. We present a historical perspective of indole synthesis showing the strategies by choosing the nitrogen precursors. The review is organized sharing the indole synthetic approaches by using different nitrogen-containing functional groups in aromatic substrates used as source of the nitrogen of the indole moiety. Some functional groups and some typical reactions are particularly stressed and highlighted because of the limited coverage given in previous reviews published on this topic. Other synthetic approaches more used and discussed in recent, complete and excellent reviews on the topic are summarized but the most recent published results are highlighted. Our interest is particularly focused on the indolization procedures and on the different methods used for the ring closure and no attention is given to modification of indole structures starting from molecules with a preformed indole unit. Intriguing indole syntheses are continually discovered and the importance that the scientific community gives to these new developments is connected with the strategic role of molecules containing the indole unit. Indoles are the class of heterocycles with more applications and extensive interest due to their biological and pharmacological activity.

The dicyclopenta[a,d]cyclooctane skeleton is obtained by a very mild Cope arrangement of the highly functionalized divinylcyclobutane derivative 10 .

Diethyl α-amino-α-alkyl-phosphonates are obtained in good to high enantiomeric excesses by alkylation of chiral phosphonoglycine equivalents embodying the camphor skeleton. The chelating effects in the alkylation step play an important role in enhancing the diastereoselectivity of the reaction as substantiated by semiempirical calculations (AM1).

Lipase-catalyzed transesterification of 2-bromo-2-cyclopenten-1-ol has been utilized in the asymmetric synthesis and consequent configurational assignment of the title compound.

A model was developed to rationalize the experimental results of the alkylation of chiral phosphonoglycine equivalents yielding α-amino-α-alkyl-phosphonates. The model studies, carried out using semiempirical calculations, have emphasized the role of the chelating effects in influencing the diastereoselectivity of the alkylation step. Chelation can be optimized by tuning the functionality of the substituent at carbon C-1 of the camphor skeleton. By employing 2d , as suggested by the modelling, a major improvement in the enantiomeric excesses of compounds 5 (R=CH 3 , C 2 H 5 ) was obtained.

A novel non-biomimetic synthesis of horsfiline has been developed. The key pyrrolidine forming reaction is the 1,3-dipolar cycloaddition of the thermally generated N -methylazomethine ylide to a suitable 3-alkylidene-indolin-2(3 H )one. The same strategy was also applied to the synthesis of pure ( R )-(−)-enantiomer.

Triethyl methanetricarboxylate (TEMT) can be mildly alkylated by primary, benzylic and allylic alcohols under classical Mitsunobu conditions, in fair to good yields. The utility of TEMT in organic synthesis as a diethyl malonate surrogate is reported.

Theoretical studies to predict the diastereoselectivity of the electrophilic amination of chiral 1,3,2-oxazaphospholanes led to the design of (1R), (2S)-1,3-diphenyl-2- (N-isopropylamino)-1-propanol 7 as a powerful chiral auxiliary. The experimental results are in good agreement with the calculations. An efficient synthesis of enantiomerically pure 7 is also reported.

The asymmetric aminohydroxylation (AA) reaction of β-substituted vinylphosphonates under Sharpless protocol followed by hydrolysis afforded β-amino-α-hydroxyphosphonic acids in moderate to good ee.

Constrained camphor-derived oxazaphospholanes have provided an efficient entry for the preparation of enantiomerically enriched α-chlorophosphonic acids.

The reaction of cyclen 1 with chloral hydrate afforded exclusively 1,4,7-triformylcyclen 2 in high yield; the triprotected macrocycle was easily alkylated with various electrophiles in good to excellent yields. The alkaline removal of the formyl groups provided a selective entry into N-monosubstituted cyclen derivatives.

The intermolecular [3 + 2] annulation of azomethine ylides with 2(2-nitrophenyl)acrylate dienophiles followed by reductive heterocyclization affords the spiro(indole-pyrrolidine) ring system. Hence, this enable us to accomplish a concise and highly enantioselective synthesis of (-)-horsfiline 1, based on chiral auxiliary-directed pi-face discrimination in the 1,3-dipolar cycloaddition of (1S,2R)-2-phenyl-1-cyclohexyl ester 4f with N-methylazomethine ylide.

We have developed a three-component, one-pot domino reaction that combines the allylindation of 1H-indole-3-carbaldehyde with the dehydrative alkylation of stabilized Cnucleophiles (e.g., electron-rich heteroarenes, electron-rich aromatics, and stabilized enols) or N nucleophiles (e.g., azoles). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

PTC-alkylation of a chiral non-racemic cyanomethyl phosphonic acid equivalent embodying the camphor skeleton gave rise to a formal entry into enantiomerically enriched β-amino-α-substituted phosphonic acids.

Reactions of aliphatic branched aldehydes with proline in dimethyl sulfoxide or acetonitrile solution afford oxazolidin-5-ones with high diastereoselection. Linear aldehydes afford aldolic/crotonic condensation products; with short reaction times, the presence of Oxazolidinones can be detected in the pmr spectra. Acyclic aminoacids and branched aldehydes yield a reaction mixture the pmr and ir spectra of which give evidence for iminic-oxazolidinone equilibria. The structure of (2R,5S)-2-trichloromethyl-1-aza-3-oxabiciclo-[3.3.0]octan-4-one has been confirmed by X-ray diffraction analysis.

Synthese par action de chlorure d'halogeno-2 acyle et de lithio-2 dithianne-1,3 sur la cyclohexene-2one suivie de reduction par le bora-9bicyclo [3.3.1] nonane puis d'hydrolyse

Ozonolysis of the ethylene acetals of 2-substituted 2-cyclohexenones followed by cyclization of the intermediate 1,6-dicarbonyl compounds affords 6-substituted 7-formyl-1,4-dioxaspiro[4,4]non-6-enes in modest yields. The same procedure applied to protected 2-substituted 2-cyclohexenols gives 2-substituted 3-formyl-2-cyclopentenyl 2-methoxyethoxymethyl ethers in satisfactory yields