Synthesis, NMR and vibrational spectroscopic characterization, and computational study of the cis-IO2F3 2- anion

The N(CH3)4(+) salt of the cis-IO2F3(2-) anion was synthesized from [N(CH 3)4][IO2F2] and excess [N(CH3)4][F] in CH3CN solvent. The [N(CH3)4] 2[IO2F3] salt was characterized by Raman, infrared, and (19)F solid-state MAS NMR spectroscopy. Geometry optimization and calculation of the vibrational frequencies at the DFT level of theory corroborated the experimental finding that the IO2F3(2-) anion exists as a single isomer with a cis-dioxo and mer-trifluoro arrangement. The fluorine atom in IO2F3(2-) that is trans to one of the oxygen atoms is weakly bound with a calculated bond length of 228.1 pm. The IO2F3(2-) anion is only the second example of an AEO 2F 3 species after XeO2F3(-).     

Synthesis,characterization, and computational study of the trans-IO2F5(2-) anion

The combination of CH(3)CN solutions of [N(CH(3))(4)][F] and a mixture of cis- and trans-[N(CH(3))(4)][IO(2)F(4)] produces the novel trans-IO(2)F(5)(2)(-) anion. Under the given conditions, only the trans-IO(2)F(4)(-) anion acts as a fluoride ion acceptor, thus allowing the separation of isomerically pure, soluble cis-IO(2)F(4)(-) from insoluble trans-IO(2)F(5)(2)(-). The trans-IO(2)F(5)(2)(-) and cis-IO(2)F(4)(-) anions were characterized by infrared and Raman spectroscopy and theoretical calculations at the LDFT and HF levels of theory. The trans-IO(2)F(5)(2)(-) anion has a pentagonal-bipyramidal geometry with the two oxygen atoms occupying the axial positions. It represents the first example of a heptacoordinated main group AO(2)X(5) species and completes the series of pentagonal-bipyramidal iodine fluoride and oxide fluoride species. The geometries of the pentagonal-bipyramidal series IO(2)F(5)(2)(-), IOF(5)(2)(-), IF(5)(2)(-), IOF(6)(-), IF(6)(-), and IF(7) and the corresponding octahedral series IO(2)F(4)(-), IOF(4)(-), IF(4)(-), IOF(5), IF(5), and IF(6)(+) were calculated by identical methods. It is shown how the ionic charge, the oxidation state of the iodine atom, the coordination number, and the replacement of fluorine ligands by either an oxygen ligand or a free valence electron pair influence the stuctures and bonding of these species.     

Concise asymmetric synthesis of (5S, 6S)- aeginetolide and (5S)- dihydroactinidiolide

An asymmetric deprotonation reaction allows for short syntheses of the lactones (5S, 6S)- Aeginetolide (1) and (5S)-Dihydroactinidiolide (2).     

Diastereoselective synthesis of (2S,5S)- and (2S,5R)-N-benzyloxycarbonyl-5-hydroxypipecolic acids from trans-4-hydroxy-l-proline

An efficient diastereoselective synthesis of cis- and trans-5-hydroxy-(2S)-N-benzyloxycarbonyl pipecolic acids, starting from trans-4-hydroxy-l-proline is described. The key synthetic strategies involve the regioisomeric ring expansion of keto ester 8 and diastereoselective reduction of ketone 11 in high selectivity and yield.     

An asymmetric synthesis of (2S,5S)-5-substituted azepane-2-carboxylate derivatives

To facilitate a drug discovery project, we needed to develop a robust asymmetric synthesis of (2S,5S)-5-substituted-azepane-2-carboxylate derivatives. Two key requirements for the synthesis were flexibility for elaboration at C5 and suitability for large scale preparation. To this end we have successfully developed a scalable asymmetric synthesis of these derivatives that starts with known hydroxy-ketone 8. The key step features an oxidative cleavage of aza-bicyclo[3.2.2]nonene 14, which simultaneously generates the C2 and C5 substituents in a stereoselective manner.     

Oxygen-bridged borate anions from tris(pentafluorophenyl)borane: synthesis, NMR characterization, and reactivity

The previously known anion [(C6F5)3B(mu-OH)B(C6F5)3]- (2) has been prepared by a two-step procedure, involving deprotonation of (C6F5)3BOH2 to give [B(C6F5)3OH]- (1), followed by addition of B(C6F5)3. The solution structure and the dynamics of 2 have been investigated by 1H and 19F NMR spectroscopy. The reaction of [NHEt3]2 with NEt3 resulted in the formation of [NHEt3]+ [(C6F5)3BOH]-, [NHEt3]+ [(C6F5)3BH]-, and (C6F5)3B- (CH2CH=N+ Et2). This indicates that in the presence of a nucleophile anion 2 can dissociate to B(C6F5)3 and 1. The reaction of [HDMAN]2 with 1,8-bis(dimethylamino)naphthalene (DMAN) confirmed this trend. In the presence of water, 2 transformed into the adduct [(C6F5)3BO(H)H...O(H)B(C6F5)3]- (3), containing the borate 1 hydrogen-bonded to a water molecule coordinated to B(C6F5)3. The same compound is formed by treating (C6F5)3BOH2 with 0.5 equiv of a base. A competition study established that for 1 the Lewis acid-base interaction with B(C6F5)3 is about 5 times preferred over H-bonding to (C6F5)3BOH2. The X-ray single-crystal analysis of [2-methyl-3H-indolium]3 provided the first experimental observation of an asymmetric H-bond in the [H3O2]- moiety, the measured O-H and H...O bond distances being significantly different [1.14(2) vs 1.26(2) A]. The reaction of NEt3 with an equimolar mixture of B(C6F5)3 and bis(pentafluorophenyl)borinic acid, (C6F5)2BOH, afforded the novel borinatoborate salt [NHEt3]+ [(C6F5)3BOB(C6F5)2]- ([NHEt3]4). X-ray diffraction showed that the B-O bond distances are significantly shorter than in [(C6F5)3B(mu-OH)B(C6F5)3]-. Variable-temperature 19F NMR revealed high mobility of the five aryl rings, at variance with the more crowded anion 2. 2D NMR correlation experiments showed that in CD2Cl2 the two anions [(C6F5)3BOH]- and [(C6F5)3BH]- form tight ion pairs with [NHEt3]+, in which the NH proton establishes a conventional (BO...HN) or an unconventional (BH...HN), respectively, hydrogen bond with the anion. The diborate anions 2-4, on the contrary, gave loose ion pairs with the ammonium cation, due both to the delocalized anionic charge and to the more sterically encumbered position of the oxygen atoms that should act as H-bond acceptors.     

Synthesis and 1H, 19F NMR spectroscopic characterization of (pentafluorophenyl)3-n (pyrazol-1-yl-tetrafluorophenyl)n=1,2 porphyrins

Three new porphyrins bearing in the meso positions 4-(pyrazol-1-yl)-2,3,5,6-tetrafluorophenyl substituents have been prepared and characterized by nmr spectroscopy.     

Enantiospecific synthesis of the sugar amino acid (2S,5S)-5-(aminomethyl)-tetrahydrofuran-2-carboxylic acid

An enantiospecific synthesis of the tetrahydrofuran amino acid (2S,5S)-5-(aminomethyl)-tetrahydrofuran-2-carboxylic acid 1 is reported. The sugar enone 2-(S)-octyl 6-O-acetyl-3,4-dideoxy-α-d-glycero-hex-3-enopyranosid-2-ulose 2a, derived from galactose, was employed as a chiral precursor. The enone 2a was converted by chemical manipulation of the functional groups into the 6-azido-2-O-tosyl-3,4,6-trideoxy-d-erythro-hexono-1,5-lactone 9 as key intermediate. Methanolysis of 9 induced the opening of the lactone and the attack of the hydroxyl group at C-5 to C-2 with the displacement of the tosylate. This reaction led to the formation of the tetrahydrofuran ring of methyl (2S,5S)-5-(azidomethyl)-tetrahydrofuran-2-carboxylate 10, which was readily converted into 1. The overall yield of the sequence was 35%, and all the intermediates and the final product have been fully characterized. In addition, the preferential conformations in solution of lactone 9 and target molecule 1 have been established.     

Lewis-base properties of the HFe3(CO)9S− and Fe3(CO)9S2− cluster anions

Summary The HFe₃(CO)₉S^– and Fe₃(CO)₉S^2– anions [prepared from H₂Fe₃(CO)₉S by deprotonation] react with M(CO)₅(THF) (M=Cr or W) to form the anionic capped clusters, HFe₃(CO)₉SM(CO) ₅ ^– and Fe₃(CO)₉SM(CO) ₅ ^2– , which can be isolated as their Et₄N salts. The M-S bonds of these complexes are cleaved by ligands such as PPh₃ or MeCN. The dianionic clusters are more stable than their monoanionic analogues. Alkylation of Fe₃(CO)₉S^2– with alkyl halides followed by protonation yields HFe₃(CO)₉SR complexes, among them the first member of the series with R=Me.     

Total synthesis of (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A and (-)-(6S,7S,8S,9R,10S)- membrenone-B and structural assignment of membrenone-C

[reaction: see text] (-)-(6S,7S,8S,9R,10S,2'S)-Membrenone-A and (-)-(6S,7S,8S,9R,10S)-membrenone-B were prepared in 11 steps (3% and 2.4% overall yield, respectively). Key steps included a tin(II)-mediated aldol followed by a syn selective reduction, giving the C7-C9 stereocenters, a second chain extending aldol coupling, and a p-TsOH-promoted cyclization/dehydration giving the common gamma-dihydropyrone precursor. We have thus established that synthetic (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A, (-)-(6S,7S,8S,9R,10S)-membrenone-B, and (-)-(6S,7S,8S,9R,10S)-membrenone-C are the enantiomers of the natural products.     

Synthesis of (2S,4S)- and (2S,4R)-5-fluoroleucine and (2S,4S)-[5,5-2H2]-5-fluoroleucine

Syntheses of (2S,4S)- and (2S,4R)-5-fluoroleucine, and, and of (2S,4S)-[5,5-(2)H(2)]-5-fluoroleucine, have been completed. The methodology allows these compounds to be prepared in sufficient quantities for incorporation by solid-state protein synthesis into strategic sites in proteins for folding studies. X-ray structures of the epimers and have been obtained and show the presence of conformational isomerism. The torsion angles between the F-C bond and the main chain are compared with values found in a mutant of the protein ubiquitin in which (2S,4S)-5-fluoroleucine replaces leucine residues 50 and 67 in the native protein.     

Structural and NMR spectroscopic investigations of chair and twist conformers of the P2Se8(2-) anion

Four new salts of the P2Se8(2-) anion have been prepared, starting from easily available reagents using different reaction strategies including reaction of the elements, oxidation of P4Se3 with alkalimetal diselenides and elemental selenium, and the use of an ionic liquid as a reaction medium. Multinuclear NMR investigations show the presence of both chair-P2Se8(2-) and twist-P2Se8(2-) in solution, with twist-P2Se8(2-) being the predominant conformer. The interconversion between the two conformers is slow on the NMR time scale. Structural investigations of the new salts by single-crystal X-ray diffraction show that chair-P2Se8(2-) is the conformer mostly found in the solid state. A first structural characterization of twist-P2Se8(2-) is reported. The bonding situation in the P2Se8(2-) anion as well as the relative stability of the chair, twist, and boat conformers was elucidated by quantum chemical calculations.     

Asymmetric synthesis of (-)-nupharamine and (-)-(5S,8R,9S)-5-(3-furyl)-8-methyloctahydroindolizidine from beta-amino ketones and the intramolecular Mannich reaction

The asymmetric synthesis of the 2,3,6-trisubstituted piperidine core of the antitumor Nuphar alkaloids was readily achieved by using the intramolecular Mannich reaction and a sulfinimine-derived beta-amino ketone.     

On the structure of passifloricin A: asymmetric synthesis of the delta-lactones of (2Z,5S,7R,9S,11S)- and (2Z,5R,7R,9S,11S)tetrahydroxyhexacos-2-enoic acid

Stereoselective syntheses of the delta-lactone of (2Z,5S,7R,9S,11S)-tetrahydroxyhexacos-2-enoic acid, the structure reported for passifloricin A, and of its (5R)-epimer are described. The creation of all stereogenic centers relied upon Brown's asymmetric allylation methodology. The lactone ring was created via ring-closing metathesis. The NMR data of both synthetic products, however, were different from those of the natural product. The published structure of passifloricin A is thus erroneous and will require further synthetic work to be unambiguously assigned. [structure: see text]     

Synthesis and evaluation of 2-(2-fluoro-4-hydroxymethyl-5-methoxy-phenoxy)acetic acid as a linker in solid-phase synthesis monitored by gel-phase (19)F NMR spectroscopy

Gel-phase (19)F NMR spectroscopy is a useful monitoring technique for solid-phase organic chemistry due to the high information content it delivers and swift acquisition times, using standard NMR spectrometers. This paper describes the synthesis of the novel linker 2-(2-fluoro-4-hydroxymethyl-5-methoxy-phenoxy)acetic acid in 29% yield over seven steps, using nucleophilic aromatic substitutions on 2,4,5-trifluorobenzonitrile as key steps. Following standard solid-phase synthesis a peptide could be cleaved from the linker using 20% TFA in CH(2)Cl(2) in 30 minutes, in contrast to a previously described monoalkoxy linker that requires 90% TFA in water at elevated temperature. A resin-bound peptide could be successfully glycosylated using only two equivalents of a thioglycoside donor, activated with N-iodosuccinimide and trifluoromethanesulfonic acid, and subsequent cleavage and deprotection gave the target glycopeptide. Direct glycosylation of the linker itself followed by mild acidic cleavage gave a fully protected hemiacetal for further chemical manipulation.     

Synthesis and redox properties of triarylmethane dye cation salts of anions [M6O19]2- (M = Mo, W)

Four salts have been isolated combining the triarylmethane dye cations pararosaniline (PR(+)) and crystal violet (CV(+)) with the hexametalates [M(6)O(19)](2-) (M = Mo, W). A new hexatungstic acid H(2)[W(6)O(19)]·4dma (dma = dimethylacetamide) was isolated and is a useful synthon for hexatungstate salts. Single-crystal X-ray diffraction confirmed the presence of PR(+) and [Mo(6)O(19)](2-) ions in [PR](2)[Mo(6)O(19)]·6dmf (dmf = dimethylformamide). A number of charge-assisted hydrogen bonds N-H···O exist between the cation -NH(2) functions and the anion oxygen atoms. Comparative cyclic voltammetry of salts [A]Cl (A = PR, CV), [Bu(4)N](2)[M(6)O(19)](2-) and A(2)[M(6)O(19)] was established in MeCN and Me(2)SO solutions and of solids in contact with the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide [emim][tfsa]. In the molecular solvents, the reversible potential for the process [Mo(6)O(19)](2-/3-) is less negative than the first reduction processes of the dye cations. In contrast, that for [W(6)O(19)](2-/3-) is more negative. Spectro-electrochemistry and bulk electrolysis experiments reveal significantly different pathways in the two cases. In contrast, in the [emim][tfsa] medium, a positive shift in reduction potential of at least 400 mV is seen for the anion processes but relatively little change for the dye cation processes. This means that initial reduction of the anions always precedes that of the dyes, providing significant simplification of the complex voltammetric data. Chemically modified electrodes can be used in the ionic liquid because of slow dissolution kinetics. However, reduced anion salts dissolve rapidly, allowing dissolved phase electrochemistry to be examined. The electrochemistries of the oxidized salts A(2)[M(6)O(19)] are essentially those of the individual ions, although low level interaction of A(+) with reduced anions [M(6)O(19)](3-,4-) is evident. The work establishes protocols for synthesis and handling of intensely absorbing and relatively insoluble salts which can now be applied to systems containing more complex polyoxometalate anions.     

Polysulfide anions II: structure and vibrational spectra of the S4(2-) and S5(2-) anions. Influence of the cations on bond length, valence, and torsion angle

The influence of the cations on bond length, valence, and torsion angle of S4(2-) and S5(2-) anions was examined in a series of solid alkali tetra- and pentasulfides by relating their Raman spectra to their known X-ray structures through a force-field analysis. The IR and Raman spectra of BaS4.H2O and the Raman spectra of (NH4)2S4.nNH3, gamma-Na2S4, and delta-Na2S5 are presented. The similarity of spectra of gamma-Na2S4 with those of BaS4.H2O suggests similar structures of the S4(2-) anions in these two compounds with a torsion angle smaller than 90 degrees. The variations of SS bond length, SSS valence angle, and dihedral angle of Sn2- anions are related to the polarization of the lone pair and electronic charge of the anion by the electric field of the cations. A correlation between the torsion angle and the SSS valence angle is shown as that previously reported between the length of the bond around which the torsion takes place and the dihedral angle value. These geometry changes are explained by the hyperconjugation concept and the electron long-pair repulsion.