The reductive dimerization of some 1,3-dienes and of 1,3,5-cycloheptatriene in the presence of trimethylchlorosilane: a DFT investigation

Treatment of 1,3-dienes and 1,3,5-cycloheptatriene by chlorotrimethylsilane in the presence of wire of lithium led mainly to reductive dimerization with formation of bis(allylsilane) derivatives. Bis-silyl compounds obtained: from 1,3-butadiene, 1,8-bis(trimethylsilyl)-2,6-octadiene (70%); from isoprene, (Z,Z)-2,7-dimethyl-1,8-bis(trimethylsilyl)-2,6-octadiene (44%) and 2,6-dimethyl-1,8-bis(trimethylsilyl)-2,6-octadiene (19%); from butadiene-isoprene mixture (1:1), 3-methyl-1,8-bis(trimethylsilyl)-2,6-octadiene (55%); from 2,3-dimethylbutadiene, (E,E)-2,3,6,7-tetramethyl-1,8-bis(trimethylsilyl)-2,6-octadiene (36%), from 1,3-cyclohexadiene, 4,4′-bis(trimethylsilyl)-bicyclohexyl-2,2′-diene (48%); from 1,3,5-cycloheptatriene, 1,1′-bi[(S^∗,S^∗)-6-(trimethylsilyl)cyclohepta-2,4-dien-1-yl] (53%). The structure of the various intermediates (radical anion, dianion, silylated radical, silylated anion) has been established by calculations at the B3LYP/6-311++G(d,p) level of theory with zero-point energy correction. These results are in accordance with a pathway including the formation of a radical anion, its silylation furnishing to a γ-silylated allylic radical followed by a dimerization reaction in the head to head manner.     

Nitroalkylation and nitroalkenylation reactions of γ-lactone enolates. A facile ring switch from polysubstituted γ-lactones to polysubstituted γ-lactams

Michael addition of lithium enolates of γ-butyrolactone 1 and α-methyl-γ-butyrolactone 1′ to (E)-1-nitropropene 2, (E)-β-nitrostyrene 3 and (E)-2-nitro-1-phenylpropene 4 is described. Reactions of the lithium enolate of 1′ with 2 and 4 occurred with high diasteroselectivity (80 and 92% d.e., respectively). Reactions of the zinc enolate of 1′ with two β-nitroenamines and two methylthio-substituted 1-amino-2-nitro-1,3-dienes were also examined. Catalytic reduction of the nitroalkylated and nitroalkenylated products allowed the achievement of functionalized γ-lactams and/or cyclic hydroxamic acids.     

Asymmetric aziridine synthesis by aza-Darzens reaction of N-diphenylphosphinylimines with chiral enolates. Part 1: Formation of cis-aziridines

The aza-Darzens (‘ADZ’) reactions of N-diphenylphosphinyl (‘N-Dpp’) imines with chiral enolates derived from oxazolidinones and camphorsultam have been studied. Whilst oxazolidinone enolates reacted poorly in terms of aziridination, the use of the chiral enolate derived from both antipodes of N-bromoacetyl 2,10-camphorsultam, 2R-(5) and 2S-(5), with N-diphenylphosphinyl aryl and tert-butylimines proceeded in generally good yield to give, respectively, (2′R,3′R)- or (2′S,3′S)-cis-N-diphenylphosphinyl aziridinoyl sultams of high de.     

N,N,N,N-Tetramethyl-1,3-propanediamine as the catalyst of choice for the Baylis-Hillman reaction of cycloalkenone: rate acceleration by stabilizing the zwitterionic intermediate via the ion-dipole interaction

N,N,N^′,N^′-Tetramethyl-1,3-propanediamine (TMPDA) can be used as an efficient catalyst for the Baylis-Hillman reaction of cycloalkenones. The increased reaction rate was thought be derived from the stabilizing effect of the zwitterionic intermediate via the ion-dipole interaction.     

Efficient preparation of 9-Z-11-methylretinal and 11-Z-11-methylretinal

[2-(β-Ionylidene)propyl]triphenylphosphonium bromide is reacted with 3-methyl-4-oxobut-2-enenitrile in refluxing 1,2-epoxybutane to give a mixture of 11-Z- and all-E-11-methylretinal via DIBAL-H reduction. In an analogous fashion, β-ionyl triphenylphosphonium bromide is reacted with 3,5-dimethyl-6-oxohexa-2,4-dienenitrile in 1,2-epoxybutane followed by subsequent DIBAL-H reduction to afford a mixture of new products consisting of 9-Z-11-methylretinal, its all-E isomer and 1-(2′,6′,6′-trimethylcyclohex-2′-en-1′-yl)-6-(buten-2″-al-3″-yl)-3,5-dimethylcyclohexa-1,3-diene. These molecules were obtained in pure form by HPLC.     

Highly selective,kinetically controlled enolate formation using lithium dialkylamides in the presence of trimethylchlorosilane

The deprotonation of ketones and esters with lithium dialkylamides in the presence of trimethylchlorosilane leads to enhanced selectivity for the kinetically generated enolate. Lithium $\text{t}$-octyl-$\text{t}$-butylamide is shown to be superior to lithium diisopropylamide in the regio-selective generation of enolates and in the stereoselective formation of $\text{E}$ enolates.     

π-Extended conjugate phenylacetylenes. Synthesis of 4-[(E) and (Z)-2-(4-ethenylphenyl)ethenyl]pyridine. Dimerization, quaternation and formation of charge-transfer complexes

The conjugate (E)- and (Z)-(4′-pyridylethenyl)-4-phenylethyne (E-4 and Z-4) has been satisfactorily prepared by two different routes: (a) by dehydrohalogenation of 4′-pyridylethenyl-4-phenyl-β-chloroethene; (b) by the Wittig reaction between p-(iodobenzyl)(triphenyl)phosphine ylide and 4-pyridinecarboxaldehyde, E/Z isomer separation, and cross-coupling with 2-methyl-but-3-yn-2-ol followed the propanone elimination. The Glaser oxidative dimerization of (Z)-4 yields (Z,Z)-1,4-di[(4′-pyridylethenyl)-4-phenyl]-buta-1,3-diyne in good yield, (Z,Z)-5. (E,E)-5 was obtained by phase transfer oxidative dimerisation of (E)-4 in presence of their N-methyl salt (E)-10. Mono- and di-N-methylated salts of conjugate (E,E)-5 and (Z,Z)-5, were obtained by quaternation with iodomethane. The (Z,Z)-5 di-N-methylated salt forms charge-transfer complexes with TCNE, TCNQ and TMPD.     

Dynamic kinetic resolution of secondary alcohols with a readily available ruthenium-based racemization catalyst

An easy to handle and stable racemization catalyst for secondary alcohols is obtained by an in situ mixture of readily available [Ru(cymene)Cl₂]₂ with chelating aliphatic diamines. Optimization of the reaction revealed that N,N,N′,N′-tetramethyl-1,3-propanediamine as ligand racemizes aromatic alcohols completely within 5 h. This easy to handle and stable catalytic system is combined with a lipase-catalyzed resolution to provide an efficient dynamic kinetic resolution of secondary alcohols.     

Investigations into the enantioselective C-protonation of prostereogenic enolate(s) derived from N,N′-diisopropyl-2-phenylpropanamide using suicide C-based proton sources

The synthesis of enantiomerically enriched (−)-(R)-N, N′-diisopropyl-2-phenylpropanamide was achieved in up to 69% enantiomeric excess by symmetrisation of the corresponding racemic amide by addition of sec-BuLi (to give the corresponding achiral lithium enolate) and subsequent desymmetrisation by the addition of a chiral C-based proton source. We discuss potential factors that may be responsible for this observed enantioselectivity and comment on the role of the chiral acid.     

Synthesis of conjugated (1E,3E)- and (1Z,3Z)-1,4-di(n-pyridyl) (or n-quinolyl)-1,3-butadienes from n-(2′-chloroethenyl)pyridine (or quinoline)

The homocoupling reaction between the conjugated n-(2-chloroethenyl)pyridine; n, 2-, 3- and 4- (or quinoline; n, 2- and 4-) mediated by zero-valent nickel complexes at room temperature affords to the corresponding 1,4-diaryl-1,3-butadiene, always as the 1E,3E stereoisomer. The yield in 1,4-diaryl-1,3-butadiene increases with the nickel catalyst and hence, the active zero-valent nickel catalyst is not regenerated during the homocoupling reaction.The stereospecific synthesis of (1Z,3Z)-1,4-di(4′-pyridyl)-1,3-butadiene stereoisomer was efficiently carried out by partial hydrogenation of the appropriate 1,4-di(4′-pyridyl)-1,3-butadiyne.     

The influence of N-alkylation and chain length in the coordination ability of diamines towards silver(I) in dimethylsulfoxide

The thermodynamic functions for the complexation of Ag(I) by the following diamines: N,N-dimethyldiethylenediamine (N,N-dmen), N,N-dimethyl-1,3-propanediamine (N,N-dmtn) and N,N,N′,N′-tetramethyl-1,3-propanediamine (tmtn) have been determined in dimethylsulfoxide (dmso) by potentiometric and calorimetric techniques at 298 K and 0.1 mol dm⁻³ ionic strength (NEt₄ClO₄). Only mononuclear complexes are formed (AgL_j ⁺, j=1, 2) where the ligands act as monodentate or chelate agents. All the complexes are enthalpy stabilized whereas the entropy changes counteract the complexation. The different basicities and steric requirements of both the ligands and complexes formed together with the size of the chelate rings are taken into account to discuss the results presented here.     

Acyclic tertiary diamines and 1,4,7,10-tetraazacyclododecane with fluorine-containing β-diketones: Leading to low melting ionic adducts

N,N,N′,N′-Tetramethylmethanediamine (1a), N,N,N′,N′-tetramethylethanediamine (1b), N,N,N′,N′-tetramethyl-1,3-propanediamine (1c), and N,N,N′,N′-tetramethyl-1,6-hexanediamine (1d) were reacted at 25 °C with 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (2a), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedione (2b), 2-thenoyltrifluoroacetone (2c), and 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione (2d) to form the ionic adducts 3-18. 1,4,7,10-Tetraazacyclododecane (1e) reacted at 25 °C with β-diketones (2a-d) and 1,1,1-trifluoro-2,4-pentanedione (2e) to give ionic solids 19-23 in good yields. Some of the products are liquid at 25 °C and are thermally stable over long liquid ranges as determined by thermal gravimetric analyses. Single-crystal X-ray structure determinations show that compounds 9 and 21 crystallize in the monoclinic space groups P2(1)/c and P2(1)/n, respectively. All the new compounds were characterized by ¹H, ¹⁹F and ¹³C NMR, electrospray MS and/or elemental analyses.     

Asymmetric aziridine synthesis by aza-Darzens reaction of N-diphenylphosphinylimines with chiral enolates. Part 2: Inversion of diastereoselectivity

The aza-Darzens (‘ADZ’) reactions of N-diphenylphosphinyl (‘N-Dpp’) imines with chiral enolates derived from N-bromoacetyl 2S-2,10-camphorsultam proceed in generally good yield to give N-diphenylphosphinyl aziridinoyl sultams. However, the stereoselectivity of the reaction is dependent upon the structure of the imine substituent: when the chiral enolate was reacted with arylimines substituted in the ortho-position, mixtures of cis- and trans-2′R,3′R-aziridines were obtained, often with a complete selectivity in favour of the trans-isomer.     

Asymmetric syntheses of 3,4-syn- and 3,4-anti-3-substituted-4-aminopiperidin-2-ones: application to the asymmetric synthesis of (+)-(3S,4R)-cisapride

The conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to δ-(N-allylamino)-α,β-unsaturated esters, followed by N-deallylation and cyclisation of the resultant β,δ-diamino esters, gives the corresponding 4-aminopiperidin-2-ones as single diastereoisomers (>99:1 dr). Subsequent deprotonation with LiHMDS and functionalisation of the resultant lithium enolate gives 3,4-anti-3-substituted-4-aminopiperidin-2-ones in >99:1 dr. Alternatively, in situ oxidation of the intermediate lithium (Z)-β-amino enolates formed upon conjugate addition gives α-hydroxy-β,δ-diamino esters, which after N-deallylation and cyclisation gives the corresponding 3,4-syn-3-hydroxy-4-aminopiperidin-2-ones in >99:1 dr. The utility of this methodology was successfully demonstrated in a concise asymmetric synthesis of the gastroprokinetic agent (+)-(3S,4R)-cisapride {(+)-(3S,4R)-N(1)-[3′-(4″-fluorophenoxy)propyl]-3-methoxy-4-(2?-methoxy-4?-amino-5?-chlorobenzamido)piperidine} in nine steps from commercially available starting materials with an overall yield of 19%.     

Highly efficient one-pot synthesis of tetrahydropyridines

The combination of aromatic aldehydes, and 1,3-dicarbonyl compounds in the presence of a catalytic amount of poly(N,N′-dibromo-N-ethyl-benzene-1,3-disulfonamide) [PBBS] and N,N,N′,N′-tetrabromobenzene-1,3-disulfonamide [TBBDA] leads to the formation of highly substituted tetrahydropyridines. In this way, a series of pharmacologically interesting substituted piperidine derivatives were obtained in moderate to high yields at room temperature.     

Addition regioselective d'enolates de cetones aux α-enones: Influence des facteurs steriques sur l'orientation et la reversibilite des reactions

Regio and stereochemistry in the addition of preformed magnesium and lithium ketone enolates (1 to 8) to α-enones (10 and 11) have been examined. When the substitution degree of the enolate is increased the formation of δ-diketone is favoured; nevertheless a good efficiency in the synthesis of the γ-ethylenic β-ketols (1-2 addition) is obtained via bromomagnesium enolates (EMgX) under kinetic conditions. Lithium enolate (ELi) and, chiefly magnesium enolates (E₂MgX) give preferentially the Michael addition. Reversibility from 1-2 to 1-4 addition is commonly observed but the stereochemistry, if any, of the diastereoisomeric δ-diLetones may be quite different when using EMgBr or E₂Mg as starting enolates.     

Stereospecific synthesis of conjugated (1E,3E)- and (1Z,3Z)-1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes from 2-chloro-1-(n-N,N-dimethylaminophenyl)ethenes: fluorescence properties

The conjugated 1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes (n=o-, m-, p-) were efficiently synthesised by homocoupling of the appropriate 2-chloro-1-(n-N,N-dimethylaminophenyl)ethene (n=o-, m-, p-) with stoichiometric amounts of zerovalent nickel complexes. The 1,3-butadienes were obtained as a mixture of stereoisomers, with independence of the starting E or Z chlorovinyl isomer. Moreover, the stereospecific (Z,Z) stereoisomer was obtained by partial hydrogenation of the corresponding 1,3-butadiyne, while the stereospecific (E,E) stereoisomer was obtained by exposure to the sunlight radiation of the (Z,Z) or the (Z,E) compound in ethanol.     

Zinc enolates: C- or O-metallation?

Two methods have been used for the generation of zinc enolates: the reaction of EtZnOMe with enol acetates, and that of lithium enolates with zinc chloride. Most of the zinc compounds prepared proved to be very reactive towards carbonyl functions, and so they cannot be isolated from the EtZnOMe/enol acetate system. The final products of these reactions are polymerisation and self-condensation products and β-diketonates, the latter being formed by condensation reactions of the zinc enolates with an acetate molecule. The structure of [EtZnOMe·Zn(Pac)₂]₂ (HPac = pivaloylacetone, (CH₃)₃CCOCH₂COCH₃), isolated in 20% yield from the reaction of EtZnOMe with CH₃COOC(t-Bu)CH₂, was determined by X-ray diffraction analysis. The compound forms monoclinic crystals, space group P2₁/c, with two dimers in a cell of dimensions a 11.677(4), b 18.299(9) and c 12.719(5) Å and β 117.26(3)°. The structure closely resembles that of the known complex [PhZnOPh·Zn(Pac)₂]₂.The complications involving reactions of zinc enolates with enol acetates were avoided by treating lithium enolates with zinc chloride. Polymerization and self-condensation could be prevented by using the very bulky enolate LiOC(t-Bu)CMe₂. In this way, the corresponding stable zinc enolate RZnCl·THF was obtained as a dissociating dimer. No replacement of the second chlorine atom by an enolate group occurred even when a large excess of lithium enolate was used.The reactivity of the zinc enolates suggests that they contain both zinccarbon and zincoxygen bonds. They are assumed to have a cyclic structure which resembles that of the Reformatsky reagent.     

rac-Lactide polymerization using aluminum complexes bearing tetradentate phenoxy-amine ligands

A family of aluminum-methyl complexes supported by tetradentate phenoxy-amine ligands has been prepared and employed in the ring-opening polymerization of rac-lactide; the ligands include N,N-bis(3,5-dimethyl-2-hydroxybenyl)-N′,N′-dimethyl-1,2-diaminoethane (L¹), N,N-bis(3,5-diisopropyl-2-hydroxybenyl)-N′,N′-dimethyl-1,2-diaminoethane (L²) and N,N-bis(3,5-dichloro-2-hydroxybenyl)-N′,N′-dimethyl-1,2-diaminoethane (L³). Polymerizations of rac-lactide were carried out by treatment of the aluminum-methyl complexes with PhCH₂OH and rac-lactide at 70 °C, affording well-controlled formation of polylactide (PLA) and a moderate isotactic bias for initiators bearing L¹ and L²; the chloro-substituted ligand L³ afforded largely atactic PLA.     

A new domino-Knoevenagel-hetero-Diels-Alder reaction

Various novel 3,5a,6,11b-tetrahydro-2H,5H-chromeno[4′,3′:4,5]thiopyrano[2,3-d][1,3]thiazol-2-ones were synthesized in 60-80% yields via domino-Knoevenagel-hetero-Diels-Alder reactions of 4-thioxo-1,3-thiazolidin-2-one with 3,7-dimethyl-6-octenal, 2-allyloxybenzaldehydes and 2-formylphenyl (E)-3-aryl-2-propenoates with base catalysis. The possibility of stereo- and regioselective cycloaddition was investigated.