Ligand's electronegativity controls the sense of enantioselectivity in BIFOP-X palladium-catalyzed allylic alkylations

Palladium-catalyzed allylic alkylations of sodium dimethyl malonate with 1,3-diphenylallyl acetate, employing BIFOP-H (biphenylbisfencholphosphite) and analogue (i.e. BIFOP-X, X = D, Cl, CN, N-3) ligands, all yield (S)-enantiomeric products, while alkylations to cyclohexenyl acetate yield the (R)-enantiomeric C-C coupling product (up to 91% yield, 70% ee). The fluoro derivative BIFOP-F however, switches the sense of enantioselectivity, yielding the (R)-enantiomer for 1,3-diphenylallyl acetate and the (S)-enantiomer for the cyclohexenyl acetate (up to 92% yield, 67% ee). Computational analyses of transition structures (M06-2X-D3/def2-TZVP//B3LYP-D3(BJ)/def2-SVP) for these Pd-catalyzed allylic alkylations reproduce the experimental preference of BIFOP-H (and analogue BIFOP-X ligands) for (R)- or (S)-enantiomeric products of 1,3-diphenylallyl or cyclohexenyl acetate, respectively. The F-switch of the sense of enantioselectivity from BIFOP-H to BIFOP-F is also apparent computationally and is found (NBO-analyses) to originate from lp(Pd) -> sigma*(P-O) or lp(Pd) -> sigma*(P-F) hyperconjugations. The higher electronegativity of F vs. H in BIFOP-X hence controls the sense of enantioselectivity of this Pd-catalyzed allylic alkylation

Electrochemical polymerization of 1,3,4,6-tetraarylpyrrolo[3,2-b]pyrrole-2,5-dione (isoDPP) derivatives

New pi-conjugated polymers containing 1,3,4,6-tetraarylpyrrolo[3,2-b] pyrrole-2,5-dione (isoDPP) units in the main chain were prepared by electrochemical polymerization of isoDPP-based monomers M1-M3. Monomers M1 and M2 were previously obtained upon palladium-catalyzed Suzuki cross-coupling of dibromo-isoDPP derivatives 3,6-bis(5-bromothiophen-2-yl)-1,4-bis(4-tert-butylphenyl) pyrrolo-[3,2-b]pyrrole-2,5-dione 1a, or 3,6-bis(5-bromothiophen-2-yl)-1,4-bis(4-hexylphenyl)-pyrrolo-[3,2-b] pyrrole2,5-dione 1b and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)-3-hexylthiophene. Monomer M3 was synthesized by Stille coupling of 1a and 2-(tributylstannyl)-4-octylthiophene. The yields were about 88%. M1-M3 were obtained as dark red powders with excellent solubility in organic solvents. The electrochemical polymerization was carried out under potentiodynamic conditions, i. e., the potential was repeatedly cycled between 0.0 (or -0.2) V and 1.2 V vs. ferrocene (FOC). The polymers P1-P3 precipitated as stable, insoluble, well adhering thin films on ITO-coated glass or glassy carbon electrodes. P1-P3 exhibit broad absorption spectra with maxima between 526 and 629 nm. They are non-fluorescent. Cyclovoltammetric studies indicate reversible oxidation and reduction behavior. Anodic cycling is accompanied with reversible colour changes of polymer films. The oxidation potentials are between 0.27 and 0.71 V vs. FOC, and the reduction potentials are between -1.21 and -1.69 V. The band gaps of the polymers are between 1.51 and 1.62 eV. Due to their optical and electrochemical properties the polymers might be useful as active materials in electrochromic displays

Enantioselective Cu-catalyzed 1,4-additions of organozinc and Grignard reagents to enones: exceptional performance of the hydrido-phosphite-ligand BIFOP-H

Enantioselective Cu-(I),Cu-(II)-(i.e. CuCl, CuCl2, Cu(OTf)(2))-catalyzed 1,4-additions of organozinc, i.e. (Et, Me)(2)Zn, and Grignard reagents, i.e. (Et, Me)MgBr, to chalcone, cyclohexenone and chromone are studied, employing fencholate-based phosphorus ligands, e.g. biphenyl-2,2-bisfenchyl hydrido phosphite = BIFOP-H. The CuClBIFOP-H-catalyzed 1,4-addition of Et2Zn to chalcone yields up to 93% and 99% ee, exceeding established BINOL- and TADDOL-based phosphoramidite ligands. Remarkably, CuCl performs better in 1,4-additions to chalcone (CuCl: 76% ee; Cu(OTf)(2): 49% ee; CuCl2: 42% ee) while Cu(OTf)(2) performs better in 1,4-additions to cyclohexenone (Cu(OTf)(2): 65% ee; CuCl: 20% ee). The computation of the reaction pathway is done for the Cu-I-catalyzed 1,4-addition to chalcone (Cu-II will be in situ reduced to Cu-I by a reagent, TPSS-D3(BJ)/def2-TZVP//B3LYP-D3(BJ)/def2-SVP) for six different model ligands, i.e. (MeO)(2)P-X (X = H, F, Me, OMe, NMe2 and PMe3). Origins of enantioselectivities are analyzed (M06-2X-D3/def2-TZVP//B3LYP-D3(BJ)/def2-SVP) for transition structures of the 1,4-methylation of chalcone with the CuBIFOP-H catalyst and explain the experimentally observed (R)-enantiomer's preference

1,6-Naphthodione-based monomers and polymers

Novel 1,6-naphthodionemonomers and p-conjugated polymers were synthesized and characterized. Monomeric 1,6-naphthodifuranones and -dipyrrolidones exhibit purple to blue colors with high extinction coefficients up to 4.6 X 104 L mol(-1) cm(-1). As shown by X-ray crystal structure analysis, the naphthodipyrrolidone core is fully planar. 1,6-Naphthodione- based polymers exhibit low band gaps (1.20-1.41 eV) and broad absorption bands (400-1000 nm). Due to their interesting electronic and optical properties, and their planar structure, naphthodione- based monomers are promising building blocks for novel p-conjugated polymers with potential applications in optoelectronics

Enantiopure Methyl- and Phenyllithium: Mixed (Carb-)Anionic Anisyl Fencholate-Aggregates

Methyl- and phenyllithium aggregates with enantiopure anisyl fencholate units form after reaction of organolithium reagent with (+)-anisyl fenchol in hydrocarbon and some ethereal solvents. These carbanionic aggregates are characterized by X-ray crystal analyses and exhibit both 3:1 stoichiometry and distorted cubic Li4O3C1 cores, in which three lithium ions coordinate the carbanion (i.e., methylide or phenylide). These three lithium ions define a Lewis acidic surface (Li-3), binding the carbanion and expanding with the steric demand of the carbanion (i.e., from Me: 2.62 angstrom(2), over n-Bu: 2.6S angstrom(2) (previous work) to Ph: 2.79 angstrom(2)). Methylation and phenylation reactions of various prochiral aldehydes employing these methyllithium and phenyllithium aggregates yield alcohols with up to 44% ee. To rationalize the formation of the mixed (carb-)anionic aggregates, aggregate formation energies, describing co-condensations of RLi (R = Me, Ph, n-Bu) and lithium fencholates, are computed for the 3:1 and 2:2 stoichiometries. These computed aggregate formation energies point to preferences for 3:1 over 2:2 aggregates, as it is also apparent from experimental aggregate formations, confirmed by X-ray crystal analyses. In close analogy to the X-ray crystal structures, the computed Li3 surfaces increase with increasing steric demand of the carbanions. The chiral, mixed (carb-)anionic RLi-fencholate aggregates hence adapt to different carbanion sized and arise not only with small (Me) or primary carbanions (n-Bu) but even with the larger secondary phenyl anion

Chiral Phosphine-Phosphite Ligands in Asymmetric Gold Catalysis: Highly Enantioselective Synthesis of Furo[3,4-d]-Tetrahydropyridazine Derivatives through [3+3]-Cycloaddition

The Au-I-catalyzed reaction of 2-(1-alkynyl)-2-alken-1-ones with azomethine imines regio- and diastereoselectively affords furo[3,4-d]tetrahydropyridazines in a tandem cyclization/intermolecular [3+3]-cycloaddition process under mild conditions. By employing a chiral gold catalyst (prepared in situ from a Taddol-derived phosphine-phosphite ligand, Me2SAuCl, and AgOTf) high yields and enantioselectivities (up to 94% yield, up to 96%ee) are obtained. The method provides an efficient modular route to substituted heterotricyclic furan derivatives and can be easily scaled up (using catalyst loads of only 0.15 mol%)

A General Stereocontrolled Synthesis of Opines through Asymmetric Pd-Catalyzed N-Allylation of Amino Acid Esters

A stereo-divergent synthesis of natural and unnatural opines in stereochemically pure form is based on the direct palladium-catalyzed N-allylation of alpha-amino acid esters (up to 97 % ee or 99 : 1 d.r.) using methyl (E)-2-penten-4-yl carbonate in the presence of only 1 mol% of a catalyst, prepared in-situ from the C-2-symmetric diphosphine iPr-MediPhos and [Pd(allyl)Cl](2). Selected target compounds (incl. a derivative of the drug enalapril) were efficiently obtained from the N-allylated intermediates by oxidative cleavage (ozonolysis) of the allylic C=C bond under temporary N-Boc-protection

Improved Synthesis of MediPhos Ligands and Their Use in the Pd-Catalyzed Enantioselective N-Allylation of Glycine Esters

A new class of chiral C-2-symmetric diphosphines (MediPhos) was recently shown to give superior results in the Pd-catalyzed asymmetric N-allylation of amino acid esters. We here describe a new, improved protocol for the preparation of such ligands through bidirectional S(N)2-coupling of a tartrate-derived ditosylate with 6-alkyl-2-bromophenols followed by double lithiation/phosphanylation. This method gave access to a series of nine ligands with branched alkyl substituents, which were benchmarked in the enantioselective Pd-catalyzed N-allylation of tert-butyl glycinate with racemic (E)-2,8-dimethylnona-5-en-4-yl methyl carbonate (up to 95 % ee). In addition, the analogous transformation of tert-butyl glycinate with methyl (E)-nona-5-en-4-yl carbonate was optimized. The obtained allylic amines were then used in the stereoselective synthesis of the conformationally restricted proline-derived dipeptide analogs ProM-17 and ProM-21

Keto-Enol Thermodynamics of Breslow Intermediates

Breslow intermediates, first postulated in 1958) are pivotal intermediates in carbene-catalyzed umpolung. Attempts to, isolate and characterize these fleeting amino enol species first met with success in 2012 when we found that saturated bis-Dip/Mes imidazolidinylidenes readily form isolable, though reactive diamino enols with aldehydes and enals. In contrast, triazolylidenes, upon stoichiometric reaction with aldehydes, :gave exclusively the keto tautomer, and no isolable enol. Herein, we present the synthesis of the missing keto tautomers of imidazolidinylidene-derived diamino enols, and computational thermodynamic data for 15 enol ketone pairs derived, from various carbenes/aldehydes. Electron-with-drawing substituents on the aldehyde favor enol formation, the same holds for N,N'-Dipp [2,6-di(2-propyl)phenyl] and N,N'-Mes [2,4,6-trimethylphenyl] substitution on the carbene component. The latter effect rests on stabilization of the diamino enol tautomer by Dipp substitution, and could be-attributed to dispersive interaction of the 2-propyl groups with the enol moiety. For three enol-ketone pairs, equilibration of the, thermodynamically disfavored tautomer was attempted, with acids and bases but could not be effected, indicating kinetic inhibition of proton transfer

Redetermination of the solvent-free crystal structure of L-proline

The title compound, (S)-pyrrolidine-2-carboxylic acid (C5H9NO2), commonly known as l-proline, crystallized without the inclusion of any solvent or water molecules through the slow diffusion of diethyl ether into a saturated solution of l-proline in ethanol. l-Proline crystallized in its zwitterionic form and the molecules are linked via N-H center dot center dot center dot O hydrogen bonds, resulting in a two-dimensional network. In comparison to the only other publication of a single-crystal structure of l-proline without inclusions [Kayushina & Vainshtein (1965). Kristallografiya, 10, 833-844], the R-1 value is significantly improved (0.039 versus 0.169) and thus, our data provides higher precision structural information