Conversion Of 1a Research Articles

Preparation of optically active cyanohydrins from 2-substituted benzaldehydes using a hydroxynitrile lyase from Pouteria sapota seeds immobilized on celite

The HNL from the defatted meal of the seeds of Pouteria sapota (PsHNL) was extracted with water, and the aqueous extract was immobilized over celite or lyophilized and used as semi-purified PsHNL. The aqueous extract was mixed with celite, ratios 1:1, 1:2 and 1:4, and lyophilized. The immobilized PsHNLdir-celite catalysed the addition of HCN to 1b in buffer saturated-DIPE (microaqueous system) with high enantioselectivity in the first cycle but diminished in the next two cycles, best results were obtained with the ratio 1:4. The reaction with PsHNLdir-celite in biphasic medium (5% citrates buffer) improved the conversion compared with the microaqueous system, but it was still lower to that obtained with the PsHNL. Other way of immobilization studied was the precipitation of the enzyme with acetone and immobilization on celite, the PsHNLpp-celite catalysed the enantioselective addition of HCN to 2-fluoro (1a), 2-chloro (1b), 2-bromo (1c), 2-methyl (1d) and 2-nitro (1e) benzaldehydes, in the biphasic medium (1:4 ratio, 5% citrates buffer). The enantiomeric excess (ee) of (R)-2a, (R)-2b, (R)-2c and (R)-2d were >98% and remained during the three cycles. The ee of 2-nitromandelonitrile was 82% and was raised to 95% in the third cycle. Compared with the PsHNL, the conversion of 1a and 1b diminished 6% and 40%, respectively, after third cycle; for 2c, conversion was almost 10% higher in the first two cycles and diminished 19% in the third; for 2d and 2e the conversion was between 18–13% and 31–18% higher, respectively.

Derivatization and biological activity studies of 3-chloro-3-chlorosulfenyl spiro tetrahydropyran/tetrahydrothiopyran-4,2'-chroman-4'-one

The adducts 4a,b-7a , b have been obtained either by reducing α-chloro-β-oxosulfenyl chlorides 2a,b with iodide ion in the presence of dienes namely, 2-methyl-1,3-butadiene (isoperene), 2,3-dimethyl-1,3-butadiene, 1,2,3,4-tetrachlorocyclopentadiene, or 1,3-cyclohexadiene, respectively; or by thermolysis of oxadithiin derivatives 3a,b in the presence of the same aforementioned dienes presumably via the formation of the same intermediate A in both cases of compounds 2a,b and 3a,b . It is observed that α-chloro-β-oxosulfenyl chlorides 2a,b undergo straight forward substitution with potassium cyanide to give 8a,b . Direct oxidation of 2a,b with H 2 O 2 /AcOH affords 3,3-dichloropyran-4-ones 9a,b , while conversion of 2a,b to the sulfonamides 10a,b followed by oxidation provides 3-chloropyranones 11a,b . Antioxidant and antimicrobial evaluation of compounds 4a,b-6a,b shows moderate activiy. MIC of the derivative 6b reveals a remarkable inhibition of the pathogenic gram positive bacteria ( Staphylococcus aureus ) as well as gram negative E coli .

Versatile coordination and C-H activation of a multi-donor phosphinoferrocene carboxamide ligand in Pd(ii) complexes.

A multi-donor phosphinoferrocene carboxamide, FcCONHCH2CH2PPh2 (1, Fc = ferrocenyl), was prepared, converted into the corresponding phosphine oxide 1O and phosphine selenide 1Se and, mainly, studied as a ligand in Pd(ii) complexes. In its native form, amide 1 preferentially coordinated soft Pd(ii) as a simple phosphine, giving rise to mixtures of cis and trans-[PdX2(1-κP)2] (2; X = Cl (a), Br (b), and I (c)), wherein the isomer ratios depended on the auxiliary halide ligand or, alternatively, to the complex [(LNC)PdCl(1-κP)] (6, LNC = 2-[(dimethylamino)methyl-κN]phenyl-κC1). This coordination mode was nevertheless easily changed when creating a vacant coordination site at the palladium. Thus, treatment of 2a with NH4[PF6] in the presence of free 1 produced [PdCl(1-κP)3][PF6] (3), while complete halogen removal with a Ag(i) salt led to cationic complexes cis-[Pd(1-κ2O,P)2]X2 (4, X = CF3SO3 (a), ClO4 (b), BF4 (c)) or [(LNC)Pd(1-κ2O,P)]X (7a and 7b), containing seven-membered O,P-chelate rings. In contrast, amide nitrogen deprotonation with KOt-Bu followed by spontaneous intramolecular halogen substitution resulted in the transformation of 6 into the chelate complex [(LNC)Pd{(1- H)-κ2N,P}] (8) featuring a five-membered N,P-chelate ring, and in the conversion of 2a and 2b into the product of C-H bond activation [Pd{Fe(η5-C5H3CONCH2CH2PPh2-κ3C,N,P)(η5-C5H5)}(1-κP)] (5), with doubly chelating deprotonated 1. Importantly, complexes 2-4-5 and 6-7-8 were mutually interconverted in triads (by protonation/deprotonation and by halide addition/abstraction), which highlights the flexible coordination and chemical stability of ligand 1. The crystal structures of 1O·½H2O, trans-2a·MeCN, trans-2b·3C2H4Cl2, trans-2c·2.5C2H4Cl2, 4a·CH2Cl2, 5·3CHCl3·Et2O, and 8 were determined by single-crystal X-ray diffraction analysis, and the representative compounds were studied by cyclic voltammetry.

3-Phenylphosphaprolines – Synthesis, structure and properties of heterocyclic α-phosphanyl amino acids

“Phenylphosphaprolines”, containing trivalent phosphorus within the five-membered ring of proline, were synthesized by cyclocondensation of 2-phenylphosphanyl ethylamines 1a,b with equimolar amounts of glyoxylic acid hydrate (GAH) or pyruvic acid in diethyl ether or 1,4-dioxane. Reaction monitoring revealed primary formation of acyclic intermediates that then converted more (1a) or less (1b) rapidly to the phosphanyl amino acids cis/trans-2a,b or cis/trans-4a,b. Ammonium-ethylphosphonium-bis(glycolate) impurities, e.g. 3b, were formed when an excess of GAH was applied. The conversion of 1a with phenylformic acid via the acyclic precursors 5a and 6a to the heterocyclic product cis/trans-7a was very slow, whereas heating of the mixture in 1,4-dioxane proceeded with decarboxylation to cis/trans-8a. The structures and diastereoisomer ratios of all new compounds were determined by 1H, 31P and 13C solution NMR spectra. The cis/trans-ratio of 2a depends on the synthetic route, i.e. addition of the phosphanylethyl amine 1a to GAH (acidic medium) or of GAH to 1a (basic medium). Furthermore, this ratio changed slowly during storage of the solution of 2a in CD3OD or methanol, indicating ring-opening ring-closure reactions and lower kinetic stability than for proline. XRD analyses established the structures of trans-2a and likewise of trans-4a and trans-8a, which from concentrated solutions crystallized in pure form.

ChemInform Abstract: First Carbamoyloxa-Bridged Cyclophane: Synthesis and Crystal Structures of Two Isolable Conformers.

Conformational control of a cyclophane with intermolecular hydrogen bonding was accomplished through the first synthesis of a carbamoyloxa-bridged cyclophane 3, with the result that the crystal structures of two isolable conformers 3a and 3b were elucidated to be anti-(E,E) and anti-(Z,Z) by X-ray analysis. The convenient conversion of 3a to 3b was carried out with hydrogen bonding assisted by polar solvents

Ferracarborane Benzene Complexes [(η-9-L-7,8-C2B9H10)Fe(η-C6H6)]+ (L = SMe2, NMe3): Synthesis, Reactivity, Electrochemistry, Mössbauer Effect Studies, and Bonding

The benzene complexes [(η-9-L-7,8-C2B9R2H8)Fe(η-C6H6)]+ (3a: L = SMe2, R = H; 3b: L = SMe2, R = Me; 3c: L = NMe3, R = H) were prepared by photochemical reaction of [(η5-C6H7)Fe(η-C6H6)]+ with carborane anions [9-L-7,8-C2B9R2H8]− (1a−c) followed by treatment of the (η-9-L-7,8-C2B9R2H8)Fe(η5-C6H7) (2a−c) ferracarboranes formed with HCl. Visible light irradiation of 3a with tBuNC or P(OMe)3 in acetonitrile results in replacement of the benzene ligand, giving the tris(ligand) derivatives [(η-9-SMe2-7,8-C2B9H10)Fe(ligand)3]+ (4, 5). The unsymmetrical carborane complex (η-9-SMe2-7,8-C2B9H10)Fe(η-9-NMe3-7,8-C2B9H10) (6) was obtained by photochemical reaction of 3a with 1c. The structures of 2a, 3aBPh4, and 6 were determined by X-ray diffraction. Temperature-dependent Mössbauer spectroscopy has been used to elucidate the hyperfine parameters and metal atom vibrational amplitudes in a number of these complexes. The redox activity of the ferracarboranes 2a,c and 3a,c has been investigated by electrochemical techniques and compared with that of the related cyclopentadienyl complexes. Electrochemistry gives evidence that the conversion of 2a−c to 3a−c can also be triggered by a two-electron oxidation followed by deprotonation. DFT calculations of the redox potentials and the respective geometrical changes were performed. Data on electrostatic potentials at iron nuclei suggest that anions 1a,c are stronger donors than Cp− in cationic complexes, but weaker donors in the neutral derivatives.

Synthesis of 1‐Methyl‐6,10‐diphenylheptalene Derivatives

AbstractThe reduction of heptalene diester 1 with diisobutylaluminium hydride (DIBAH) in THF gave a mixture of heptalene‐1,2‐dimethanol 2a and its double‐bond‐shift (DBS) isomer 2b (Scheme 3). Both products can be isolated by column chromatography on silica gel. The subsequent chlorination of 2a or 2b with PCl5 in CH2Cl2 led to a mixture of 1,2‐bis(chloromethyl)heptalene 3a and its DBS isomer 3b. After a prolonged chromatographic separation, both products 3a and 3b were obtained in pure form. They crystallized smoothly from hexane/Et2O 7 : 1 at low temperature, and their structures were determined by X‐ray crystal‐structure analysis (Figs. 1 and 2). The nucleophilic exchange of the Cl substituents of 3a or 3b by diphenylphosphino groups was easily achieved with excess of (diphenylphospino)lithium (=lithium diphenylphosphanide) in THF at 0° (Scheme 4). However, the purification of 4a/4b was very difficult since these bis‐phosphines decomposed on column chromatography on silica gel and were converted mostly by oxidation by air to bis(phosphine oxides) 5a and 5b. Both 5a and 5b were also obtained in pure form by reaction of 3a or 3b with (diphenylphosphinyl)lithium (=lithium oxidodiphenylphospanide) in THF, followed by column chromatography on silica gel with Et2O. Carboxaldehydes 7a and 7b were synthesized by a disproportionation reaction of the dimethanol mixture 2a/2b with catalytic amounts of TsOH. The subsequent decarbonylation of both carboxaldehydes with tris(triphenylphosphine)rhodium(1+) chloride yielded heptalene 8 in a quantitative yield. The reaction of a thermal‐equilibrium mixture 3a/3b with the borane adduct of (diphenylphosphino)lithium in THF at 0° gave 6a and 6b in yields of 5 and 15%, respectively (Scheme 4). However, heating 6a or 6b in the presence of 1,4‐diazabicyclo[2.2.2]octane (DABCO) in toluene, generated both bis‐phosphine 4a and its DBS isomer 4b which could not be separated. The attempt at a conversion of 3a or 3b into bis‐phosphines 4a or 4b by treatment with t‐BuLi and Ph2PCl also failed completely. Thus, we returned to investigate the antipodes of the dimethanols 2a, 2b, and of 8 that can be separated on an HPLC Chiralcel‐OD column. The CD spectra of optically pure (M)‐ and (P)‐configurated heptalenes 2a, 2b, and 8 were measured (Figs. 4, 5, and 9).

Palladium(II)‐catalyzed catalytic aminocarbonylation and alkoxycarbonylation of terminal alkynes: regioselectivity controlled by the nucleophiles

AbstractThe aminocarbonylation and alkoxycarbonylation reactions of terminal alkynes took place smoothly and efficiently using a catalyst system Pd(OAc)2–dppb–p‐TsOHCH3CNCO under relatively mild experimental conditions. The catalytic system was tested and optimized using two different nucleophiles: alcohols and amines. Phenylacetylene (1a) was considered as an alkyne along with diisobutylamine (2b1) and methanol (2c1) as nucleophiles. The results showed significant differences in the conversion of 1a and in the selectivity towards the gem or trans unsaturated esters or amides with these nucleophiles. The effects of the type of palladium catalysts, the type of ligands, the amount of dppb and the solvents were carefully studied. With diisobutylamine (2b1), excellent regioselectivity towards the 2‐acrylamides (gem isomer, 3ab1) was almost always observed, while trans‐α,β‐unsaturated esters 4ac1 was the predominant product with methanol (2c1) as a nucleophile. This remarkable sensitivity in the selectivity of the reaction indicates two different possible mechanistic pathways for these carbonylation reactions. Copyright © 2009 John Wiley & Sons, Ltd.

Synthesis of 3-Benzyl- or 3-Benzoyl-7,8-dihydro-6H-chromene Derivatives Starting from Baylis-Hillman Adducts

acetate 1 and cyclohexane-1,3-dione (2a) in the presence of K2CO3 in DMF gave 3a in 68% yield. Conversion of 3a into the corresponding lactone derivative 4a was conducted by refluxing 3a in p-xylene to give 4a in 59% yield. The exodouble bond of 4a could be isomerized in its endo-position by treatment with DMAP (4,4-dimethylaminopyridine) in refluxing p-xylene to give 5a in 89% yield. As easily expected, the reaction of 3a in the presence of DMAP in refluxing p-xylene gave 5a in 75% yield directly. In addition, compound 5a was synthesized directly from the reaction of 1 and 2a in 78% yield without separation of the intermediate 3a as also shown in Scheme 1. As a next trial, we examined the allylic oxidation of 4a and 5a, and we found that the reaction of 4a and PCC (pyridinium chlorochlomate) produced the 3-benzoyl derivative 6a in 63% yield. 11 However, the oxidation of 5a with PCC showed no reaction. Like this we found efficient syn

Ruthenium‐Catalyzed Oxidation of Secondary Alcohols Assisted by a Simple Alkene.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of 3‐Benzyl‐2‐hydroxy‐7,8‐dihydro‐6H‐quinolin‐5‐ones from Baylis—Hillman Adducts.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Ruthenium-Catalyzed Oxidation of Secondary Alcohols Assisted by a Simple Alkene

The oxidation of alcohols to carbonyl compounds has been recognized as a fundamental organic transformation in synthetic organic chemistry. Besides conventional routes, many elegant transition metal-catalyzed methods assisted by co-oxidants are known and used for such transformations. As part of our ongoing studies on ruthenium catalysis, it has recently been found that carbonyl compounds are coupled with alcohols in several routes. The coupling of ketones 1 with primary alcohols 2 preferentially afforded coupled ketones 4 (Scheme 1, route a) or coupled secondary alcohols 5 (Scheme 1, route b) according to the molar ratio of 2 to 1. In addition, secondary alcohols 3 was also found to be coupled with 2 to give 5 (Scheme 1, route c). Among them, in connection with this report, the addition of sacrificial hydrogen acceptor (1-dodecene) in the case shown in route c of Scheme 1 was essential for the dramatic enhancement of reaction rate. This could be due to the acceleration of initial oxidations of both starting alcohols by transfer hydrogenation from alcohols to 1-dodecene. Under these circumstances, this report describes a rutheniumcatalyzed oxidation of secondary alcohols in the presence of 1-dodecene. The results of several attempted oxidations of 1-(2naphthyl)ethanol (3a) to 2'-acetonaphthone (4a) under several conditions are listed in Table 1. Treatment of 3a in the presence of a catalytic amount of RuCl2(PPh3)3 (2 mol%) along with KOH in dioxane at 100 C afforded 4a in 15% isolated yield with 35% conversion of 3a (run 1). However, when 1-dodecene was further added, the oxidation rate was remarkably enhanced and 4a was formed in 77% yield with 85% conversion of 3a (run 2). As has been noted in our recent report, the fate of 1-dodecene seems to be partially converted into dodecane by accepting hydrogen. It is known that the carbon-carbon double bond of α,βunsaturated carbonyl compound works as a hydrogen acceptor for the ruthenium-catalyzed oxidation of secondary alcohols to ketones. Lower reaction temperature (80 C) resulted in a slightly lower yield of 4a (run 3). Performing the reaction under K2CO3/toluene in place of KOH/dioxane produced 4a in only 41% yield with incomplete conversion (43%) (run 4). Similar treatment of 3a in the presence of RhCl(PPh3)3 under the employed conditions resulted in lower yield of 4a (60%) when compared to the use of RuCl2(PPh3)3 catalyst (run 5). Given the controlled reaction conditions, various secondary alcohols 3 were employed to investigate the reaction scope. The results are summarized in Table 2. Aryl(methyl) carbinols (3b-3e) were oxidized into the corresponding ketones (4b-4e) in the range of 21-79% yields. The ketone yield was considerably affected by the electronic nature of the substituent on the aromatic ring of aryl(methyl) cabinols. With 3c and 3d having electron-donating substituent on the Scheme 1 Table 1. Oxidation of 3a into 4a under several conditionsa

Synthesis of 3-Benzyl-2-hydroxy-7,8-dihydro-6H-quinolin-5-ones from Baylis-Hillman Adducts

2-Hydroxy-7,8-dihydro-6H-quinolin-5-one skeleton is a useful backbone for the synthesis of numerous biologically interesting compounds such as carbostyrils (2-hydroxyquinolines) or huperzine A analogues, which have shown biological activities including non-steroidal antiinflammatory activity, acetylcholinesterase (AChE) inhibitory activity and antimalarial activity. During the studies on the chemical transformation of the Baylis-Hillman adducts toward synthetically useful heterocyclic compounds we envisioned that we could synthesize 3-benzyl-5-methoxycarbostyril derivatives 5. Our synthetic rationale for 5a is depicted in Scheme 1. Reaction of the Baylis-Hillman acetate 1 and cyclic enaminone 2 would provide the tetrahydroquinoline-2,5-dione skeleton 3 via SN2' type reaction of cyclic enaminones to the BaylisHillman acetates followed by amide bond formation. We thought that the following iodine-assisted oxidative aromatization of cyclohexenone moiety and base-catalyzed isomerization of lactam moiety would afford the desired 3benzyl-5-methoxycarbostyril derivative 5. The reaction of Baylis-Hillman acetate 1a and 3-amino-2cyclohexenone (2a) in refluxing ethanol in the presence of catalytic amount of acetic acid gave 3-benzylidene-4,6,7,8tetrahydro-1H,3H-quinoline-2,5-dione (3a) as the major product (52%) together with small amounts of 4a (< 10%). The reaction could also be conducted in n-butanol without acetic acid catalyst in a similar pattern. But, when we used nbutanol as the solvent, 4a was observed as the major product on TLC presumably due to the effect of higher reaction temperature than in EtOH. But, 3a was not changed completely into 4a even after heating for a long time. Thus we examined the conditions for the effective transformation of 3a into 4a and we found a suitable condition fortunately. Conversion of 3a into 4a could be carried out easily with catalytic amounts of DBU in THF at room temperature (reflux for the conversion of 3g into 4g, entry 7 in Table 1). Thus, we prepared 4a-c according to the following procedures: reaction of 1a-c and 2a in refluxing n-BuOH, separation of 3 and 4 as a mixtures, and finally DBU treatment to form 4a-c as the final products (entries 1-3 in Table 1). It is interesting to note that the easiness for the conversion

Homochiral oxazolidin-2-ones and imidazolidin-2-ones by tandem nucleophilic addition–conjugate addition

Treatment of both primary alcohols 1a, b and secondary amines 1c, d, tethered to a Michael acceptor with ( R)-phenylethyl isocyanate in the presence of DBU gave in good yield and high stereoselection diastereomeric mixtures of oxazolidin-2-ones 2a, b and 3a, b and imidazolidin-2-ones 2c, d and 3c, d, respectively. The cyclisation reaction was studied computationally by ab initio quantum mechanical methods. The observed stereoselectivity was explained on the basis of the different stability of both anions and transition states leading to 2a and 3a, respectively. The usefulness of the method was proven by conversion of 2a into the enantiomerically pure bioactive amino acid 5.

Silylated amino-triazines: new ligands with potential multi-coordination modes

Melamine ( 1a), 2,4-diamino-6-phenyl-1,3,5-triazine ( 1b), and 2,4-diamino-6-methyl-triazine ( 1c) react with chlorotrimethylsilane and triethylamine in refluxing acetonitrile to give the corresponding monosilylated products 2a–c in good yields. Conversion of 2a–c to the lithium silylamides with n-BuLi occurs readily, as evidenced by a subsequent reaction with chlorodimethylsilane. The silylamides show promise as chelating ligands with the possibility of multi-coordination bonding modes.

The reaction of homophthalic acid and some aza analogues with vilsmeier reagent: a reinvestigation

AbstractHomophthalic acid and its pyrido and 8‐methylquinolino analogues with dimethylformamide/phosphoryl chloride at 0° give the appropriate 4‐(dimethylaminomethylene)isochroman‐1,3‐dione (2a, 2b, 2c, respectively). Under the literature conditions for conversion of 2a to 2‐methyl‐1‐oxo‐1,2‐dihydroisoquinoline‐4‐carboxylic acid (3a), the aza analogues give instead 7‐hydroxy‐5‐oxo‐5H‐pyrano[4,3‐b]pyridine‐8‐carbox‐aldehyde (5b) and 3‐hydroxy‐6‐methyl‐1‐oxo‐1H‐pyrano[4,3‐b]quinoline‐4‐carboxaldehyde (5c), respectively. Modified conditions were required to isolate analogues 3b and 3c. Further, while reaction of 2a with hydrogen chloride in methanol gave the known change to methyl 1‐oxo‐1H‐isochromene‐4‐carboxylate (4), 2b and 2c gave only products of oxa‐ring cleavage. Methyl 2‐(cis‐2‐hydroxyvinyl)‐8‐methylquinoline‐3‐carboxylate (8) was the main product from 2c, while a novel quinolizinium species (11) was formed in good yield from 2b.

A Radical and An Electron Transfer Process Are Compared in Their Regioselectivities Towards A Molecule with Two Different C−I Bonds: Effect of Steric Congestion

Steric compression in 1,4-diiodo-2,6-dimethylbenzene (2a) makes the C−I bond flanked by methyls substantially weaker (a buttressing effect) than the unhindered C−I bond. Calculations also confirm the weaker bonding interaction of the hindered C−I bond of 2a. This causes a remarkable regioselectivity toward the weaker bond in dehalogenation by stannyl radicals. Conversely, a much lower regioselectivity is found for a process −a photostimulated SRN1 reaction with the enolate ion of a ketone − which requires the conversion of 2a into a radical anion. A calculation of the BDE of the C−I bond for aa ArI•− system is offered. Finally, the hindered aryl radical intermediate resulting from cleavage of the weaker C−I bond of 2a•− shows a modest but detectable discrimination between reduction or substitution, this once again being due to the steric congestion.

Synthesis and Solid State Structures of Sterically Congested Sodium and Cesium Silyl(fluorosilyl)phosphanide Aggregates and Structural Characterization of the Trimeric Sodium Bis(trimethylsilyl)amide

Metalation of the silyl(fluorosilyl)phosphane Is2(F)Si−PH(SiR3) (3a; Is = 2,4,6-triisopropylphenyl, R3Si = Me2(PriMe2C)Si) at phosphorus with NaN(SiMe3)2 (4) in the molar ratio of 1:1 in toluene leads to the solvent-free sodium derivative 1a which forms a Na2P2-dimer in solution and in the solid state. The coordinatively unsaturated Na centers are each additionally bonded to a fluorine atom, so that a ladder-like, puckered tricyclic F2Na2P2Si2 skeleton results as the central structural motif. The same conversion of 3a into 1a under less polar reaction conditions (hexane) and the complete conversion of the silyl(fluorosilyl)phosphane Is2(F)Si−PH(SiPri3) (3b) into its Na derivative 1b is kinetically hampered and can only be achieved if 2 equiv of sodium amide 4 are employed. Excess 4 may be recovered by fractional crystallization, from which its molecular Na3N3-trimer was isolated and structurally characterized for the first time. The unusual molecular polymeric cesium phosphanide [Is2(F)Si−PCs(SiPri3)·0.5THF] (2) was prepared by the metalation of 3a with elemental cesium in toluene in the presence of little THF. The structure of 2 was determined by X-ray diffraction.

Synthesis of N-Demethyl-N-substituted 14b-Hydroxy-isomorphine and Dihydroisomorphine Derivatives

Some new representatives (3e-3h, 5g) of a new group of structurally related morphine-agonist and antagonist compounds have been prepared in stereochemically homogeneous forms. Application of the Mitsunobu-reaction for suitable codeine derivatives (1a-1d) gave the benzoates (2a-2d) of the hitherto unknown C-6 iso-compounds, which were converted into the desired isocodeines (3b-3d) by means of alkaline hydrolysis. O-Demethylation of these derivatives afforded the corresponding morphine analogues. The preparation of 3e was also carried out from 1f via compound (2e). A hitherto unknown N-demethylation also allowed the conversion of 3a and 5a into the target compounds. With the exception of N-allyl derivatives, the dihydro analogues were obtained by the hydrogenation of the C 7 -C 8 double bond

Transfer hydrogenation of ketones with [Ru4H3(CO)12]? as the precatalyst

The cluster [N(PPh3)2][Ru4H3(CO)12]1a has been found to be an efficient precatalyst for the transfer hydrogenations of ketones and α,β-unsaturated ketones. With substrates such as (5S)-carvone [2-methyl-5-(1-methylethenyl)cyclohex-2-en-1-one], (3R)-methylcyclopentanone and (3R)-methylcyclohexanone, moderate to high diastereoselectivities were observed for reduction of the conjugated olefinic and ketonic functionalities respectively. Aromatisation of carvone to 5-isopropyl-2-methylphenol and disproportionation of cyclohex-2-en-1-one to phenol and cyclohexanone have also been found to be catalysed by 1a. Studies with radical inhibitors and other evidence suggest a radical mechanism for the transfer-hydrogenation and aromatisation reactions. In the transfer hydrogenation of cyclohex-2-en-1-one, the rate of conversion of 1a into other soluble species can be modelled accurately if autocatalysis is assumed. The time-dependent concentration profiles of cyclohex-2-en-1-one, cyclohexanone and cyclohexanol are simulated well if autocatalytic formation of an active intermediate followed by consecutive reactions leading to the formation of products is assumed. Such a model is also consistent with the proposed radical mechanism.