Tatiana Soler

Functionalization of Methyl (R)-Phenylglycinate Through Orthopalladation: C−Hal, C−O, C−N, and C−C Bond Coupling

The ortho functionalization of methyl R-phenylglycinate has been easily achieved using the known orthopalladated complex [Pd(mu-Cl){R-C(6)H(4)(CH(CO(2)Me)NH(2))-2}](2) (1) as synthetic tool. Different functional groups have been introduced at the ortho position of the aryl ring. The reaction of (R)-1 with X(2) or PhI(OAc)(2) gives XC(6)H(4)(CH(CO(2)Me)NH(2))-2 (X = I, Br, OMe, OEt) through oxidative coupling, while the reaction with CO gives an isoindolone. (R)-1 also reacts with one, two, or three alkyne molecules to give different metal-containing or metal-free heterocycles. The resulting functionalized amino esters or heterocycles retain the chirality of (R)-1, according with the values of the optical rotation and the obtained ee values ranging from 22%-87%. The X-ray structures of six representative compounds have also been determined.

Reversible single-crystal-to-single-crystal cross-linking of a ribbon of cobalt citrate cubanes to form a 2D net.

An unprecedented 1-D polymer of cobalt citrate cubanes, 1, has been prepared by wet chemistry techniques and isolated as single crystals with two units of formula Cs2Co7(citr)4(H2O)21 in the unit cell [H4citr = C6H8O7, citric acid], as characterized by X-ray diffraction at T = 278 K. In addition to the four Co atoms in the cubane unit, there are four independent peripheral citrate-bound Co sites. Upon warming at T = 303 K, the polymer undergoes cross-linking through a complex substitution/addition reaction at one of the peripheral Co centers to produce a new 2-D polymer based on the same Co citrate cubane building block. In the transition a second peripheral Co atom undergoes a substitution reaction and separates from the polymer. The new phase, 2, analyzed by X-ray diffraction from the same crystalline sample as 1, has two units of formula Cs2Co7(citr)4(H2O)13.5 in the unit cell. Water egress in the transition amounts to 35.7 mole percent. The volume of the unit cell diminishes by 12.4%. The Co center at...

Structural modification of carbohydrates via functionalised organolithium intermediates: EPC preparation of branched-chain functionalised sugars

Abstract The reductive opening of epoxides 1, 9, 13 derived from d -glucose and 18 derived from d -fructose using lithium and a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB) in THF at −78°C allows the formation of β-oxido organolithium derivatives (2, 10, 14 and 19), which, by reaction with different electrophiles [H2O, D2O, Me3SiCl, PhCHO, Me2CO, Et2CO, (CH2)5CO, CO2] at the same temperature yields, after hydrolysis with water, the expected branched-chain functionalised carbohydrates. An alternative route for compound 11, derived from the epoxide 9, consists of the deprotonation of the chlorohydrin 12 followed by the same protocol of lithiation-reaction with an electrophile. The application of this methodology to the oxetane 4 allows compound 6 to be obtained through the corresponding γ-functionalised organolithium intermediates 5. Finally, the addition of the dianions 25 (resulting from the DTBB-catalysed lithiation of phthalan and isochroman) to the ketones 8 and 23, derived from d -glucose and d -fructose, respectively, allowed the stereoselective functionalisation at the 3-position of the sugars, giving the corresponding diols 26 and 27, which can cyclise to the corresponding heterocycles 28 and 29, respectively, under Mitsunobu reaction conditions.

Regioselective Orthopalladation of (Z)-2-Aryl-4-Arylidene-5(4H)-Oxazolones: Scope, Kinetico-Mechanistic, and Density Functional Theory Studies of the C–H Bond Activation

Orthopalladated complexes derived from (Z)-2-aryl-4-arylidene-5(4H)-oxazolones have been prepared by reaction of the oxazolone with palladium acetate in acidic medium. The reaction is regioselective, only the ortho C-H bond of the arylidene ring being activated, producing a six-membered ring. The scope and reaction conditions of the orthopalladation are dependent on the acidity of the solvent. In CF(3)CO(2)H a large number of oxazolones can be metalated under mild conditions. As acidity decreases a lesser number of oxazolones can be efficiently palladated and harsher conditions must be used to achieve similar yields. The C-H bond activation in acidic medium agrees with an ambiphilic mechanism, as determined from kinetic measurements at variable temperature and pressure for different oxazolones substituted at the arylidene ring. The mechanism has been confirmed by density functional theory (DFT) calculations, where the formation of the six-membered ring is shown to be favored from both a kinetic and a thermodynamic perspective. In addition, the dependence of the reaction rate on the acidity of the medium has also been accounted for via a fine-tuning between the C-H agostic precoordination and the proton abstraction reaction in the overall process occurring on coordinatively saturated [Pd(κ(N)-oxazolone)(RCO(2)H)(3)](2+).

Cyclopalladation and reactivity of amino esters through C-H bond activation: Experimental, kinetic, and density functional theory mechanistic studies

The orthopalladation, through C-H bond activation, of a large number of amino esters and amino phosphonates derived from phenylglycine, and having different substituents at the aryl ring and the C-α atom, as well as on the N-amine atom, has been studied. The experimental observations indicated an improvement in the yields of the orthopalladated compounds when the N-amine and/or the C-α atom are substituted, when compared with the unsubstituted methyl phenylglycinate derivatives. In contrast, substitutions at the aryl ring do not promote significant changes in the orthometalation results. Furthermore, the use of hydrochloride salts of the amino esters has also been shown to have a remarkably favorable effect on the process. All these observations have been fully quantified at different temperatures and pressures by a detailed kinetic study in solution in different solvents and in the presence and absence of added Brønsted acids and chloride anions. The data collected indicate relevant changes in the process depending on these conditions, as expected from the general background known for cyclopalladation reactions. An electronic mechanism of the orthopalladation has been proposed based on DFT calculations at the B3LYP level, and a very good agreement between the trends kinetically measured and the theoretically calculated activation barriers has been obtained. The reactivity of the new orthopalladated amino phosphonate derivatives has been tested and it was found that their halogenation, alkoxylation and carbonylation resulted in formation of the corresponding functionalized ortho-haloaminophosphonates, ortho-alkoxyaminophosphonates and oxoisoindolinylphosphonates.

Synthesis of functionalised enantiopure steroids from estrone and cholestanone through organolithium intermediates

Abstract The reaction of epoxides 1 and 8 derived from estrone and cholestanone, respectively, with an excess of lithium and a catalytic amount of DTBB (7 mol%) in THF at −78°C led to formation of the corresponding β-oxido-functionalised organolithium intermediates 2 and 9 , respectively, in a regio- and stereoselective manner. Treatment of these intermediates with different electrophiles [H 2 O, D 2 O, PhCHO, Me 2 CO, Et 2 CO, (CH 2 ) 5 CO, CO 2 ] at −78 to 20°C afforded, after hydrolysis with water, enantiomerically pure derivatives 3 and 10 , respectively. When protected ketones 5 and 6 derived from d -glucose and d -fructose were used as the electrophile, the reaction with 2 gave the expected mixed products 3g and 3h , respectively, which consist of a steroid and a carbohydrate fragment. The reaction of O -protected estrone 4 as the electrophilic component and intermediate 2 afforded the C 2 -symmetric steroid dimer 3f . The stereochemistry of the products was unambiguously determined by correlation with X-ray data for compound 3d and by comparison with the known compound 6a . Finally, the addition of the dianions 13 , resulting from the DTBB-catalysed lithiation of phthalan 12a and isochroman 12b , to the O -protected estrone 4 and to cholestanone 9 led to the formation of the diols 14 , 15 and 16 . Diols 14 were cyclised under Mitsunobu reaction conditions to the corresponding heterocycles 17 .

Branched-chain functionalised carbohydrates via β-functionalised organolithium compounds

Abstract The reaction of the epoxysugar 1 with an excess of lithium powder and a catalytic amount of DTBB (5 mol%) in THF at −78°C leads to the formation of the corresponding β-oxido functionalised organolithium intermediates 2, which by treatment with different electrophiles [H2O, D2O, Me3SiCl, PhCHO, Me2CO, (CH2)5CO] at −78°C to room temperature afford, after hydrolysis with water, the expected enantiomerically pure compounds 3. Starting from the epimeric epoxide 4 and following the same procedure, using water as electrophile, the compound 6 was isolated, the correponding intermediate 5 having been involved in the process.

Synthesis, Structure, and Reactivity of N-Benzoyl Iminophosphoranes Ortho Lithiated at the Benzoyl Group

Ortho lithiation of N-benzamido-P,P,P-triaryliminophosphoranes through deprotonation with alkyllithium bases was achieved with ortho-C═O and ortho-P═N chemoselectivity. However, the synthetic scope of these processes was rather limited. Ortho-lithiated N-benzamido-P,P,P-triphenyliminophosphorane 8 was efficiently prepared via lithium/halogen exchange of the corresponding ortho-brominated precursor with s-BuLi in THF at -90 °C. The reaction of 8 with a variety of electrophiles provides an easy and mild method for the regioselective synthesis of ortho-modified iminophosphoranes via C-C (alkylation and hydroxyalkylation) and C-X (X = I, Si, P, Sn, and Hg) bond-forming reactions. NMR characterization of 8 in THF solution showed that 8 exists as an equilibrium mixture of one monomer and two dimers. The Li atoms of these species become members of five-membered rings through chelation by the ortho-metalated carbon and the carbonyl oxygen. The dimers differ in the relative orientation of the two chelates with respect to the plane defined by the C(2)Li(2) core. The equilibrium between all species is established by splitting the dimers into monomers and subsequent recombination with formation of a different dimer.

Unexpected [2 + 2] C–C bond coupling due to photocycloaddition on orthopalladated (Z)-2-aryl-4-arylidene-5(4H)-oxazolones

A [2 + 2] photocycloaddition has been observed in regioselectively orthopalladated 2-aryl-4-arylidene-5(4H)-oxazolones, leading to unprecedented cyclobutane-bis(oxazolones).

Structural modification of steroids through functionalised organolithium compounds

Abstract The reaction of the epoxysteroids 1 and 4 , derived from estrone and cholestanone, respectively, with an excess of lithium and a catalytic amount of DTBB (7 mol%) in THF at −78°C, leads to the formation of the corresponding β-oxido-functionalised organolithium intermediates 2 and 5 , respectively, which, by reaction with different electrophiles [H 2 O, D 2 O, PhCHO, Me 2 CO, Et 2 CO, (CH 2 ) 5 CO, CO 2 ] at −78°C to room temperature, afford, after hydrolysis with water, enantiomerically pure compounds 3 and 6 , respectively. The stereochemistry of all these compounds was unambiguously determined by correlation with X-ray data for compound 3d and by comparison with the known compound 6a .