Enantioselective Synthesis: Steric and electronic effects of the substrates upon stereoselectivity in the gold(I)-catalyzed aldol reaction with chiral ferrocenylamine ligands,preliminary communication

Enantioselectivity in the gold(I)-catalyzed aldol reaction with chiral ferrocenylamine ligands is strongly dependent upon both the steric and electronic effects of the substrates. In the reaction of pyridine-2-, 3-, and 4-carbaldehydes with ethyl 2-isocyanoacetate, surprisingly and significantly different enantioselectivities were observed in the formation of the cis- and trans-dihydro-oxazoles that must be due to electronic rather than steric effects. The first example of double stereodifferentiation in the gold(l)-catalyzed aldol reaction is reported.     

The crystal structure of tetraethylammonium aquatetracyanooxorhenate(V)

Summary The crystal structure of the tetraethylammonium salt of [ReO(H₂O)(CN)₄]^– has been determined from threedimensional x-ray diffraction data. The light blue crystals are monoclinic, space group P2₁/m witha=8.760(1),b=9.518(5),c=11.718(1) Å, =102.63(1)^o with two molecules per unit cell. The final R value using 2009 observed reflections and anisotropic thermal parameters for all the non-hydrogen atoms was 0.038. The [ReO(H₂O)(CN)₄]^– ion has a distorted octahedral geometry with the rhenium atom displaced by 0.30 Å out of the plane formed by the four carbon atoms of the cyano ligands towards the oxo ligand. Bond distances: Re=O=1.667(8), Re–OH₂=2.142(7) and Re–C (average)=2.11(1) Å.     

Synthesis of pyrimido[4,5-e][1,4]oxazepin-5-ones

Eighteen novel pyrimido[4,5-e][1,4]oxazepin-5-ones were prepared directly via the reaction of either ethyl 4-chloro-2-phenyl-5-pyrimidinecarboxylate (Ia) or ethyl 4-chloro-2-m-chlorophenyl-5-pyrimidinecarboxylate (Ib) with a variety of substituted 2-(alkylamino)ethanols. A typical example was the preparation of 8,9-dihydro-9-methyl-2-phenylpyrimido[4,5-e][1,4]-oxazepin-5(7H)-one (IIa) from the reaction of Ia with 2-(methylamino)ethanol. Hydrolytic cleavage of the lactone ring in IIa with sodium hydroxide solution, followed by acidification with hydrochloric acid afforded 4-[(2-hydroxyethyl)methylamino]-2-phenyl-5-pyrimidinecarboxylic acid (IV). Reactions of IIa with concentrated ammonium hydroxide or hydrazine also caused cleavage of the lactone ring, giving the corresponding amide (V) or hydrazide (VI), respectively. Structural assignments were supported by infrared and nuclear magnetic resonance spectra.     

A simple relationship between the hammett acidity function,Ho, and the thermodynamic pKa values of unsubstituted aromatic carboxamides

The well-known failure of the Hammett H_o function to describe the prototropic reaction isotherms of aromatic carboxamides can be corrected by taking account of the hydration requirements of the prototropic reactions of the carboxamides relative to the hydration requirements of the dissociations of the primary amines used as indicators to establish the H_o scale. This approach has been successfully applied to benzamide and the naphthamides. For up to a 4:1 molar ratio of water to sulfuric acid, the amide acidity scale, H_A and the H_o scale are simply related by H_A = H_o — 2 log a_w , where a_w is the activity of water.     

Gibberellin metabolites from ent-kaura-2,16-dien-19-ol and its succinate in Gibberella fujikuroi

Exposure of ent-kaura-2,16-dien-19-ol (1) or its succinate (2) to resuspended mycelia of G. fujikuroi has produced a complex mixture of acids which after methylation gave the esters of two C₁₉ (24) and (30) and five C₂₀ gibberellins (4, 11, 20, 32 and 33). The triester (32) and the lactone ester (24) have been prepared before from the esters of gibberellin A₁₃ (8) and gibberellin A₄ (26) respectively. The structures of the other metabolites were assigned on spectroscopic data and by chemical transformations. Thus the lactone diester (4) has been converted to the known keto triester (6). The epoxide (11) has been related to gibberellin A₁₄ (14) and the aldehyde (33) has been related to gibberellin A₁₃ trimethyl ester (8) by way of the triol (34). Selective de-epoxidation of the 16,17-epoxy function in diepoxides has provided a route from the dienes (20 and 24) to the epoxides (11 and 30) respectively, but not from the ester of gibberellin A₅ (23) to that of gibberellin A₆ (29). On the other hand the latter can be obtained by epoxidation of gibberellin A₅ methyl ester trifluoroacetate. Backfeeding experiments carried out with the epoxy diacid (12), the diene diacid (21) and the derived diol (39) indicate pathways connecting the various metabolites. The natural gibberellins A₅ and A₆ were shown to be formed in some of the backfeeding experiments.     

Thieno[2,3-d]pyrimidines. I. A new method for the preparation of esters and amides of thieno[2,3-d] pyrimidine-6-carboxylic acids

A novel method for the preparation of esters and amides of thieno[2,3-d]pyrimidine-6-carb-oxylic acids was described. A typical example was the direct formation of ethyl 5-amino-2-methylthiothieno[2,3-d]pyrimidine-6-earboxylate(IIIa) from 4-chloro-2-methylthio-5-pyrimidine-carbonitrile (Ia) and ethyl mercaptoacetate in refluxing ethanol containing sodium carbonate. Displacement of the methylthio group in IIIa by various amines gave the corresponding amino derivatives. The reactions of IIIa and related compounds with acetylating agents such as acetic anhydride or chloroacetyl chloride gave various products. Treatment of 5-carbethoxy-4-chloro-2-phenylpyrimidine(IV) with methyl mercaptoacetate afforded the dechloro intermediate diester Va, which cyclized on reaction with sodium ethoxide to form methyl 5-hydroxy-2-phenylthieno-[2,3-d]pyrimidine-6-carboxylate (Vla). The synthesis was expanded to include the preparation of various new 2,4,5-trisubstituted thieno[2,3-d]pyrimidine-6-carboxylic acid esters and amides (Charts I-V).     

Derivatisation for liquid chromatography/electrospray mass spectrometry: synthesis of pyridinium compounds and their amine and carboxylic acid derivatives

A simple method has been developed for the pre-column derivatisation of low molecular weight primary and secondary amines and carboxylic acids using quaternary nitrogen compounds to enhance their detection by liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS). The synthesis of seven novel quaternary nitrogen reagents is described. The derivatives are designed to be relatively small molecules to avoid some of the steric hindrance problems that may be associated with larger derivatisation reagents. The compounds have amine and carboxylic acid functional groups with which to derivatise carboxylic acids and amines, respectively. Two of the compounds contain a bromine atom in order to assess the advantages of a bromine isotope pattern in the mass spectra. This acts as a simple marker for derivatisation and enables data processing by cluster analysis.Activation of the carboxylic acid group was achieved by the use of either 1-chloro-4-methylpyridinium iodide (CMPI) or the more reactive 1-fluoro-4-methylpyridinium p-toluenesulphonate (FMP).1 Using both of these active reagents, the degree of nucleophilic substitution was investigated for the derivatisation of a variety of small molecules. Whilst giving some increase in the ESI-MS response for the derivatised compounds, the FMP itself acted as a derivatising reagent in a competing reaction. In the light of this finding, FMP was reacted with the test compounds separately and gave positive results as a derivatising reagent. Detection of the 'pre-charged' derivatives of amines and carboxylic acids by LC/ESI-MS was investigated with respect to their ESI response and chromatography.     

Effect of varying counterions on the sensitivity of electrohydrodynamic and fast atom bombardment mass spectrometry

The abundance of ion pairs (CA⁺) relative to that of doubly charged ions (C²⁺) in electrohydrodynamic (EH) mass spectra of a series of anions with a common dication in glycerol was found to increase in the order acetate < nitrite < chloride < bromide ≈ nitrate < iodide < perchlorate. Correlation with enthalpies of hydration for the anions suggests that this trend reflects the solution chemistry of ion association. These spectra also reveal that solvation rather than interactions with the extracting field is more important in determining the overall EH mass spectrometric sensitivity to doubly charged ions. Therefore, the use of anions that promote more extensive ion pairing enhances the overall sensitivity to multiply charged ions that otherwise interact strongly with the solvent, but reduces sensitivity to singly charged ions. These observations hold in fast atom bombardment mass spectrometry, surviving the invasive effects of the primary beam.     

S)-(+)-2-(p-tolylsulfinyl)-2-buten-4-olide: an enantiomerically pure Michael acceptor for asymmetric synthesis of 3-substituted 4-butanolides. (—)-podorhizon.

A short, reliable, and practical synthesis of ($\text{S}$)-(+)-2-($\text{p}$-tolylsulfinyl)-2-buten-4-olide has been developed, and the utility of this Michael acceptor for highly enantiocontrolled synthesis of 3-substituted 4-butanolides has been demonstrated.     

Core model calculation of the electric field gradient: Projection operator formalism with application to NH3

A core model approach to the calculation of deuteron quadrupole coupling constants is investigated using NH₃ as an example. First the deuteron quadrupole coupling constant is calculated from a CNDO wave function. This result is subsequently improved by recomputing the N—D bond orbital by means of a variational calculation using the CNDO function to construct a core potential for the bond Hamiltonian. In order to simplify integrations a single-center basis is chosen to represent the variational wave function. A projection operator formalism is used as a computational scheme to maintain orthogonality of the bond orbital to core orbitals. Excellent agreement with experiment is obtained. The procedure is applicable to more complicated molecules.