E- or Z-Selective synthesis of 4-fluorovinyl-1,2,3-triazoles with fluorinated second-generation Julia-Kocienski reagents.

A highly modular approach to N-substituted 4-(1-fluorovinyl)triazoles is described. In situ desilylation and Cu-catalyzed ligation reaction of TMS-protected α-fluoropropargyl benzothiazole sulfone with aryl, alkyl, and metallocenyl azides furnished second-generation Julia-Kocienski reagents in good to excellent yields. Condensation reactions of these reagents with aldehydes can be tuned to yield E or Z-alkenes selectively. Under mild conditions with DBU as the base, reactions of aldehydes furnished E-alkenes as the major isomer. On the other hand, in condensation reactions with LHMDS as the base and in appropriate solvents, both aldehydes and ketones reacted to yield fluoroalkenes with Z-selectivity. Stereochemical assignment of E/Z olefins obtained in the reaction of a ketone with two Julia reagents was performed via X-ray crystallographic analysis and comparisons of NMR data. The method allows efficient and ready diversification of the N1-substituent and substituents at the double bond.

High-yielding aqueous 18F-labeling of peptides via Al18F chelation.

The coordination chemistry of a new pentadentate bifunctional chelator (BFC), NODA-MPAA 1, containing the 1,4,7-triazacyclononane-1,4-diacetate (NODA) motif with a methylphenylacetic acid (MPAA) backbone, and its ability to form stable Al(18)F chelates were investigated. The organofluoroaluminates were easily accessible from the reaction of 1 and AlF(3). X-ray diffraction studies revealed aluminum at the center of a slightly distorted octahedron, with fluorine occupying one of the axial positions. The tert-butyl protected prochelator 7, which can be synthesized in one step, is useful for coupling to biomolecules on solid phase or in solution. High yield (55-89%) aqueous (18)F-labeling was achieved in 10-15 min with a tumor-targeting peptide 4 covalently linked to 1. Defluorination was not observed for at least 4 h in human serum at 37 °C. These results demonstrate the facile application of Al(18)F chelation using BFC 1 as a versatile labeling method for radiofluorinating other heat-stable peptides for positron emission imaging.

On the two-component microwave-mediated reaction of isonitriles with carboxylic acids: regarding alleged formimidate carboxylate mixed anhydrides.

Microwave induced two-component coupling (2CC) reaction of carboxylic acids with isonitriles gives rise to various N-formylamides. The formimidate carboxylate mixed anhydride (FCMA) is proposed as the reactive intermediate, which undergoes 1,3-O-->N acyl transfer to give the observed product. The formation and survival of the labile FCMA system has been evaluated.

Synthesis of the AB subunit of angelmicin B through a tandem alkoxy radical fragmentation-etherification sequence.

The synthesis of the tricyclic enone 2, corresponding to the AB subunit of the novel tyrosine kinase inhibitor angelmicin B, is described. The strategy centers on an intramolecular Diels-Alder (IMDA) reaction on triene 4 to provide the complex decalin 3, which is elaborated to 2. Other key steps are the formation of the THF ring in 2 through a tandem alkoxy radical fragmentation-etherification on the lactol derived from 3, and the synthesis of 4 via a ring-closing ene-yne metathesis (RCEYM).

Cyclic peptoids.

Foldamers are an intriguing family of biomimetic oligomers that exhibit a propensity to adopt stable secondary structures. N-Substituted glycine oligomers, or "peptoids", are a prototypical example of these foldamer systems and are known to form a helix resembling that of polyproline type I. Ongoing studies seek to improve the stability of peptoid folding and to discover new secondary structure motifs. Here, we report that peptoids undergo highly efficient head-to-tail macrocyclization reactions. A diverse array of peptoid sequences from pentamers to 20mers were converted to macrocyclic products within 5 min at room temperature. The introduction of the covalent constraint enhances conformational ordering, allowing for the crystallization of a cyclic peptoid hexamer and octamer. We present the first X-ray crystallographic structures of peptoid hetero-oligomers, revealing that peptoid macrocycles can form a reverse-turn conformation.

Efficient microwave-assisted synthesis of amine-substituted tetrakis(pentafluorophenyl)porphyrin.

We report an efficient and rapid means for the synthesis of tetrakis(pentafluorophenyl)porphyrin (TPPF(20)) derivatives by microwave irradiation in an environmentally acceptable solvent. The selective displacement of the para-fluorine groups in TPPF(20) by primary amines occurs in yields between 70 and 95%. This method demonstrates that TPPF(20) is an ideal platform for the rapid formation of porphyrin conjugates for therapeutic, catalytic, and other applications. [reaction: see text]

Influence of steric and electronic properties of the defect site, lanthanide ionic radii, and solution conditions on the composition of lanthanide(III) alpha1-P2W17O6110- polyoxometalates.

This study identifies the principles that govern the formation and stability of Ln complexes of the (alpha(1)-P(2)W(17)O(61))(10-) isomer. The conditional stability constants for the stepwise formation equilibria, K(1cond) and K(2cond), determined by (31)P NMR spectroscopy, show that the high log K(1cond)/log K(2cond) ratio predicts the stabilization of the 1:1 Ln/ (alpha(1)-P(2)W(17)O(61))(10-) species. The value of log K(1cond) increases as the Ln series is traversed, consistent with the high charge/size requirement of the basic alpha(1) defect site. The conditional stability constants, K(2), are very low and are highly dependent on the countercations in the buffer. The source of the instability is understood from the crystal structures of the early-mid lanthanide analogues, where the close contact of the (alpha(1)-P(2)W(17)O(61))(10-) units result in severe steric encumbrance. The electronic properties of the alpha(1) defect along with the lanthanide ionic radii and countercation composition are important parameters that need to be considered for a rational synthesis of lanthanide polyoxometalates.

Stereoselective synthesis of P-chiral phosphorus compounds from N-tert-butoxycarbonyl amino acids.

Reaction of the N-t-Boc amino acids alanine and valine with PhPCl(2) gives the P-chiral trans-1,3,2-oxazaphospholidinones exclusively. Variable-temperature NMR and examination of the glycine derivative shows that the isomers observed are due to t-Boc rotation.

Why are silyl ethers conformationally different from alkyl ethers? Chair-chair conformational equilibria in silyloxycyclohexanes and their dependence on the substituents on silicon. The wider roles of eclipsing, of 1,3-repulsive steric interactions, and of attractive steric interactions.

An NMR study of the diaxial/diequatorial chair equilibrium in a range of silylated derivatives of trans-1,4- and trans-1,2-dihydroxycyclohexane is reported and discussed with a view to explaining unusually large populations of chair conformations with axial substituents, noted previously for some monosilyloxycyclohexanes and in some silylated sugars. X-ray diffraction studies of three bis-triphenylsilyloxycyclohexanes are reported and show both axial and equatorial silyloxy groups with the exocyclic bonds eclipsed. Eclipsing is also suggested by molecular mechanics (MM3) calculations on such derivatives. Both axial and equatorial tertiary silyl groups have 1,3-repulsive interactions with whatever substituents or hydrogen atoms are at the two adjacent equatorial positions, and these are relieved by rotation toward the eclipsed conformation of the exocyclic C-O bond. The three substituents on silicon interact attractively with the nine atoms at the 3, 4, and 5-positions of the cyclohexane ring and calculations suggest that these stabilizing interactions are significantly greater in the axial than in the equatorial conformation. An equatorial C-OSiR(3) bond with one or two equatorial neighbors has a restricted potential energy well that becomes much broader when the bond is axial without any equatorial neighbors in the alternative chair. Adjacent silyl groups in the 1,2-disubstituted series interact in a stabilizing way overall in all conformations, this being particularly marked in the diaxial conformation of the more complex ethers. These factors lead to unusually large axial populations.