Catalysis of the beta-elimination of HF from isomeric 2-fluoroethylpyridines and 1-methyl-2-fluoroethylpyridinium salts. Proton-activating factors and methyl-activating factors as a mechanistic test to distinguish between concerted E2 and E1cb irreversible mechanisms

Second-order rate constants, k(OH)(N), M(-)(1) s(-)(1), for the beta-elimination reactions of HF with 2-(2-fluoroethyl)pyridine (2), 3-(2-fluoroethyl)pyridine (3), and 4-(2-fluoroethyl)pyridine (4) in OH(-)/H(2)O, at 50 degrees C and mu = 1 M KCl, are = 0.646 x 10(-)(4) M(-)(1) s(-)(1), = 2.97 x 10(-)(6) M(-)(1) s(-)(1), and = 5.28 x 10(-)(4) M(-)(1) s(-)(1), respectively. When compared with the second-order rate constants for the same processes with the nitrogen-methylated substrates 1-methyl-2-(2-fluoroethyl)pyridinium iodide (5), 1-methyl-3-(2-fluoroethyl)pyridinium iodide (6), and 1-methyl-4-(2-fluoroethyl)pyridinium iodide (7), the methyl-activating factor (MethylAF) can be calculated from the ratio k(OH)(NCH)3/, and a value of 8.7 x 10(5) is obtained with substrates 5/2, a value of 1.6 x 10(3) with 6/3, and a value of 2.1 x 10(4) with 7/4. The high values of MethylAF are in agreement with an irreversible E1cb mechanism (A(N)D(E) + D(N)) for substrates 5 and 7 and with the high stability of the intermediate carbanion related to its enamine-type structure. In acetohydroxamate/acetohydroxamic acid buffers (pH 8.45-9.42) and acetate/acetic acid buffers (pH 4.13-5.13), the beta-elimination reactions of HF, with substrates 2 and 4, occur at NH(+), the substrates protonated at the nitrogen atom of the pyridine ring, even when the [NH(+)] is much lower than the [N], the unprotonated substrate, due to the high proton-activating factor (PAF) value observed: 3.6 x 10(5) for 2 and 6.5 x 10(4) for 4 with acetohydroxamate base. These high PAF values are indicative of an irreversible E1cb mechanism rather than a concerted E2 (A(N)D(E)D(N)) mechanism. Finally, the rate constant for carbanion formation from NH(+) with 2 is k(B)(NH)+ = 0.35 M(-)(1) s(-)(1), which is lower than when chlorine is the leaving group ( = 1.05 M(-)(1) s(-)(1); Alunni, S.; Busti, A. J. Chem. Soc., Perkin Trans. 2 2001, 778). This is direct experimental evidence that some lengthening of the carbon-leaving group bond can occur in the intermediate carbanion. This is a point of interest for interpreting a heavy-atom isotope effect.     

Multireference perturbation CI I. Extrapolation procedures with CAS or selected zero-order spaces

We discuss the “three class” approximation to full multireference perturbation CI, which greatly reduces the computational effort by restricting the summation of diagrams to determinants belonging to a subspace of the zero-order space. In the framework of the CIPSI algorithm, we propose a new extrapolation procedure allowing recovery of the full “two class” results. The new procedure is applied to complete active spaces (CAS) and to individually selected zero-order spaces. Comparison with a full two class calculation on a CAS shows a reduction of computer time of one or two orders of magnitude in the tests presented here, with an accuracy in the order of 0.1 kcal/mol. Our procedure can thus compete with the CASPT2 algorithm, specifically conceived to deal with CAS. In the case of selected zero-order spaces, the speed-up is less dramatic but the method still retains its advantages. Received: 12 June 1997 / Accepted: 31 July 1997     

Experiences in the measurement of RBC-bound IgG as markers of cell age

An immunologically mediated pathway has been largely accepted to be one of the mechanisms involved in the clearance of senescent or prematurely damaged RBC. According to this pathway, RBC removal is mediated by binding of naturally occurring IgG to clustered integral membrane proteins, followed by complement deposition. The validation of an immunoenzymatic method for the detection of RBC-bound autologous IgG is presented. The use of RBC-bound IgG as an index related to red cell age was evaluated by measuring IgG binding in RBC treated with the clustering agent ZnCl2, in density fractionated RBC and in a selected group of patients expected to have an altered RBC life span. The immunoenzymatic method for IgG detection resulted to be reproducible (CV = 3.4%). IgG binding to in vitro clustered RBC was found to be enhanced to a very great extent, about 20 times higher with respect to untreated RBC. A slight but significant increase (about 1.8-fold) in membrane-bound IgG was observed in the highest density fraction of normal RBC, which constituted 1% of the total cells. A significantly greater number of RBC-bound IgG was measured in splenectomized beta-thalassemia intermedia patients and in subjects with secondary decreases in the C3 complement fraction concentration.     

On the direct calculation of the time evolution of excited molecular states in the presence of nonadiabatic interactions

The possibility is explored of calculating the time evolution of a given initial molecular state, in the presence of sufficiently strong nonadiabatic interactions, with a fully quantum-mechanical approach. Two methods are presented. The first one is based on the determination of the molecular eigenstates, with expansion of the nuclear wavefunctions on a Hermite basis. The second method is based on the Padé 1,1 approximation of the time evolution operator and on a finite difference representation of the time-dependent nuclear wavefunctions. Both methods are applied to simple models of a diatomic molecule.     

Dienic sex pheromones : Stereoselective syntheses of (7E,9Z)-7,9-dodecadien-1-yl acetate, (E)-9,11-dodecadien-1-yl acetate,and of (9Z), 11E)-9,11- tetradecadien-1-yl acetate by palladium-catalyzed reactions

Pure (7E,9Z-7, 9-dodecadien-1-yl acetate (1), the sex pheromone of Lobesiabotrana, has been prepared in 21.6% overall yield by a reaction scheme involving; (i) the cross-coupling of (E) - 8 - (2 - tetrahydropyranyloxy) -1 - octenyldisiamylborane with 1 - bromo - 1 - butyne, in the presence of a Pd (O) catalyst and base; (ii) the acetylation of the crude product of this reaction; (iii) the (Z)-stereoselective reduction of the obtained conjugated (E)-enyn-1-yl acetate. (E)-9,11-Dodecadien-1-yl acetate (2), a sex pheromone component of Diparopsiscastanea, has been analogously obtained (in 54.3% overall yield) by cross-coupling of (E) - 10 - (2 - tetrahydropyranyloxy) - 1 - decenyl borane with vinyl bromide, in the presence of a Pd (O) catalyst and base, followed by acetylation of the crude product. Compound 2, which was 87.7% chemically pure, was purified by column chromatography over SiO₂-AgNO₃. Chemically pure (9Z, 11E) - 9,11 - tetradecadien - 1 - yl acetate (3), a sex pheromone component of Spodopteralittoralis, has been prepared (in 30.2% overall yield) by reaction of 10 - (2 - tetrahydropyranyloxy) - 1 - decynylamagnesium bromide with (E)-1-iodo-1-butene, in the presence of a Pd (O) catalyst, followed by acetylation of the crude product and by (Z)-stereoselective reduction of the obtained (E)-enyn-1-yl acetate.The stereoisomeric purity of 1, 2 and 3 has been evaluated by glc analysis on glass capillary columns or by reverse phase hplc analysis.     

Synthesis of [Ir3Rh(CO)12] and Fluxional Behaviour of Some of Its Substituted Derivatives

The redox condensation of [Ir(CO)₄]^–, [Ir(cod)(THF)₂]⁺, and [Rh(cod)(THF)₂]⁺ (cod = cycloocta-1,5-diene) followed by saturation with CO (1 atm) in THF afforded the first synthetic route to pure [Ir₃Rh(CO)₁₂] ( 1 ). Substitution of CO by monodentate ligands gave [Ir₃Rh(CO)₈(μ₂-CO)₃L] (L = Br^–, 2 ; I^–, 3 ; bicyclo[2.2.1]hept-2-ene, 4 ; PPh₃, 5 ). Clusters 2 – 5 have C_s symmetry with the ligand L bound to the basal Rh-atom in axial position. They are fluxional in solution at the NMR time scale due to two CO scrambling processes: the merry-go-round of basal CO's and changes of basal face. An additional process takes place in 5 above room temperature: the intramolecular migration of PPh₃ from the Rh- to a basal Ir-atom. Substitution of CO by polydentate ligands gave [Ir₃Rh(CO)_7–x(μ₂-CO)₃(η⁴-L)x] (L = bicyclo[2.2.1]hepta-2,5-diene (= norbornadiene; nbd), x = 1, 6 ; L = nbd, x = 2, 13 ; L = cod, x = 1, 7 ; L = cod x = 2, 15 ), [Ir₃Rh(CO)₇(μ₂-CO)₃(η²-diars)] (diars = 1,2-phenylenebis-(dimethylarsine); 8 ), [Ir₃Rh(CO)₇(μ₂-CO)₃(η⁴-L)] (L = methylenebis(diphenylphosphine), bonded to 2 basal Ir-atom ( 9a ) or one Ir- and one Rh-atom ( 9b )), [Ir₃Rh(CO)₆(μ₂-CO)₃(η⁴-nbd)PPh₃] ( 12 ), and [Ir₃Rh(CO)₆(μ₂-CO)₃(μ₃-L)] (L = 1,3,5-trithiane, 10 ; L = CH(PPh₂)₃, 11 ). Complexes 6 – 8 , 9a , 10 , and 11 have C_s symmetry, the others C₁ symmetry. They are fluxional in solution due to CO scrambling processes involving 1, 3, or 4 metal centres as deduced from 2D-EXSY spectra. Comparison of the activation energies of these processes with those of the isostructural Ir₄ and Ir₂Rh₂ compounds showed that substitution of Ir by Rh in the basal face of an Ir₄ compound slows the processes involving 3 or 4 metal centres (merry-go-round and change of basal face), but increases the rate of carbonyl rotation about an Ir-atom.     

Asymmetric Synthesis of Highly Enantiomerically Enriched (S)(-)-β-Bisabolene

(S)-β-Bisabolene, (S)-1, was synthetized by a synthetic route in which (S)-4-methyl-3-cyclohexene carboxylic acid, (S)-10, which was the key intermediate, was prepared via a highly diastereoselective TiCl₄-catalyzed Diels-Alder reaction between isoprene and the acrylate of commercial (R)-pantolactone, followed by hydrolysis. Compound (S)-10 was then converted into ketone (S)-13 using two different procedures. The best one of these, as regards the degree of stereospecificity, involved the reaction of (S)-10 with 2 equiv of 4-methyl-3-penten-1-yllithium, 14, in the presence of CeCl₃, and gave (S)-13 having ca. 84% ee. The Zr-promoted methylenation of this ketone afforded highly enantiomerically enriched (S)-1.     

Synthesis and Transformations of NH-Sulfoximines

Recent years have seen a marked increase in the occurrence of sulfoximines in the chemical sciences, often presented as valuable motifs for medicinal chemistry. This has been prompted by both pioneering works taking sulfoximine containing compounds into clinical trials and the concurrent development of powerful synthetic methods. This review covers recent developments in the synthesis of sulfoximines concentrating on developments since 2015. This includes extensive developments in both S−N and S−C bond formations. Flow chemistry processes for sulfoximine synthesis are also covered. Finally, subsequent transformations of sulfoximines, particularly in N-functionalization are reviewed, including N−S, N−P, N−C bond forming processes and cyclization reactions.