FeIII -Based Eutectic Mixtures as Multi-task and Reusable Reaction Media for Efficient and Selective Conversion of Alkynes into Carbonyl Compounds.

Invited for the cover of this issue is the group of Vicente del Amo, Alejandro Presa Soto and Joaquín García-Álvarez (QuimSinSos Group) at the University of Oviedo. The image depicts the use of the FeIII -based deep eutectic mixture [FeCl3 ⋅6 H2 O/Gly (3:1)] (Gly = glycerol) as both promoter and solvent for the straightforward and selective hydration of alkynes, working under mild (45 °C), bench-type reaction conditions (air) and in the absence of ligands, co-catalysts or co-solvents. Read the full text of the article at 10.1002/chem.202301736.

FeIII -Based Eutectic Mixtures as Multi-task and Reusable Reaction Media for Efficient and Selective Conversion of Alkynes into Carbonyl Compounds.

An efficient, simple and general protocol for the selective hydration of terminal alkynes into the corresponding methyl ketones has been developed by using a cheap, easy-to-synthesise and sustainable FeIII -based eutectic mixture [FeCl3 ⋅ 6H2 O/Gly (3 : 1)] as both promoter and solvent for the hydration reaction, working: i) under mild (45 °C) and bench-type reaction conditions (air); and ii) in the absence of ligands, co-catalysts, co-solvents or toxic, non-abundant and expensive noble transition metals (Au, Ru, Pd). When the final methyl ketones are solid/insoluble in the eutectic mixture, the hydration reaction takes place in 30 min, and the obtained methyl ketones can be isolated by simply decanting the liquid FeIII -DES, allowing the direct isolation of the desired ketones without VOC solvents. By using this straightforward and simple isolation protocol, we have been able to recycle the FeIII -based eutectic mixture system up to eight consecutive times. Furthermore, the FeIII -eutectic mixture is able to promote the selective and efficient formal oxidation of internal alkynes into 1,2-diketones, with the possibility of recycling this system up to three consecutive times. Preliminary investigations into a possible mechanism for the oxidation of the internal alkynes seem to indicate that it proceeds through the formation of the corresponding methyl ketones and α-chloroketones.

From oximes to tertiary alcohols in water, at room temperature and under air: a hybrid one-pot tandem assembly of enzymatic deoximation and RLi/RMgX reagents.

The highly efficient biodeoximation of aromatic ketoximes, promoted by the enzymatic oxidative system laccase/TEMPO/O2, has been successfully assembled with the fast and chemoselective addition of highly-polar s-block organometallic reagents (RLi/RMgX) en route to highly-substituted tertiary alcohols. By using this hybrid one-pot tandem protocol, tertiary alcohols have been selectively synthesized in good yields and under mild and bench-type reaction conditions (room temperature, the absence of a protecting atmosphere and aqueous media, which are non-typical conditions for polar organometallic reagents). The overall hybrid one-pot tandem transformation amalgamates two distant organic synthetic tools (RLi/RMgX reagents and enzymes) without the need for any tedious and energy/time-consuming intermediate isolation/purification steps.

A one-pot two-step synthesis of tertiary alcohols combining the biocatalytic laccase/TEMPO oxidation system with organolithium reagents in aerobic aqueous media at room temperature.

The one-pot/two-step combination of enzymes and polar organometallic chemistry in aqueous media is for the first time presented as a proof-of-concept study. The unprecedented combination of the catalytic oxidation of secondary alcohols by the system laccase/TEMPO with the ultrafast addition (3 s reaction time) of polar organometallic reagents (RLi/RMgX) to the in situ formed ketones, run under air at room temperature, allows the straightforward and chemoselective synthesis of tertiary alcohols with broad substrate scope and excellent conversions (up to 96%).

Copper-catalyzed Goldberg-type C-N coupling in deep eutectic solvents (DESs) and water under aerobic conditions.

An efficient and selective N-functionalization of amides is first reported via a CuI-catalyzed Goldberg-type C-N coupling reaction between aryl iodides and primary/secondary amides run either in Deep Eutectic Solvents (DESs) or water as sustainable reaction media, under mild and bench-type reaction conditions (absence of protecting atmosphere). Higher activities were observed in an aqueous medium, though the employment of DESs expanded and improved the scope of the reaction to include also aliphatic amides. Additional valuable features of the reported protocol include: (i) the possibility to scale up the reaction without any erosion of the yield/reaction time; (ii) the recyclability of both the catalyst and the eutectic solvent up to 4 consecutive runs; and (iii) the feasibility of the proposed catalytic system for the synthesis of biologically active molecules.

Combination of organocatalytic oxidation of alcohols and organolithium chemistry (RLi) in aqueous media, at room temperature and under aerobic conditions.

A tandem protocol to access tertiary alcohols has been developed which combines the organocatalytic oxidation of secondary alcohols to ketones followed by their chemoselective addition by several RLi reagents. Reactions take place at room temperature, under air and in aqueous solutions, a trio of conditions that are typically forbidden in polar organometallic chemistry.

Fast and Chemoselective Addition of Highly Polarized Lithium Phosphides Generated in Deep Eutectic Solvents to Aldehydes and Epoxides.

Highly polarized lithium phosphides (LiPR2 ) were synthesized, for the first time, in deep eutectic solvents as sustainable reaction media, at room temperature and in the absence of protecting atmosphere, through direct deprotonation of both aliphatic and aromatic secondary phosphines (HPR2 ) by n-BuLi. The subsequent addition of in-situ generated LiPR2 to aldehydes or epoxides proceeded quickly and chemoselectively, thereby allowing the straightforward access to the corresponding α- or ß-hydroxy phosphine oxides, respectively, under air and at room temperature (bench conditions), which are traditionally considered as textbook-prohibited conditions in the field of polar organometallic chemistry of s-block elements.

Cylindrical Micelles by the Self-Assembly of Crystalline-b-Coil Polyphosphazene-b-P2VP Block Copolymers. Stabilization of Gold Nanoparticles.

During the last number of years a variety of crystallization-driven self-assembly (CDSA) processes based on semicrystalline block copolymers have been developed to prepare a number of different nanomorphologies in solution (micelles). We herein present a convenient synthetic methodology combining: (i) The anionic polymerization of 2-vinylpyridine initiated by organolithium functionalized phosphane initiators; (ii) the cationic polymerization of iminophosphoranes initiated by -PR2Cl2; and (iii) a macromolecular nucleophilic substitution step, to prepare the novel block copolymers poly(bistrifluoroethoxy phosphazene)-b-poly(2-vinylpyridine) (PTFEP-b-P2VP), having semicrystalline PTFEP core forming blocks. The self-assembly of these materials in mixtures of THF (tetrahydrofuran) and 2-propanol (selective solvent to P2VP), lead to a variety of cylindrical micelles of different lengths depending on the amount of 2-propanol added. We demonstrated that the crystallization of the PTFEP at the core of the micelles is the main factor controlling the self-assembly processes. The presence of pyridinyl moieties at the corona of the micelles was exploited to stabilize gold nanoparticles (AuNPs).

Organolithium-Initiated Polymerization of Olefins in Deep Eutectic Solvents under Aerobic Conditions.

Despite their ubiquitous presence in synthesis, the use of polar organolithium reagents under environmentally benign conditions constitutes one of the greatest challenges in sustainable chemistry. Their high reactivity imposes the use of severely restrictive protocols (e.g., moisture- and oxygen-free, toxic organic solvents, inert atmospheres, low temperatures, etc.). Making inroads towards meeting this challenge, a new air- and moisture-compatible organolithium-mediated methodology for the anionic polymerization of different olefins (e.g., styrenes and vinylpyridines) was established by pioneering the use of deep eutectic solvents (DESs) as an eco-friendly reaction medium in this type of transformation. Fine-tuning of the conditions (sonication of the reaction mixture at 40 °C in the absence of protecting atmosphere) along with careful choice of components of the DES [choline chloride (ChCl) and glycerol (Gly) in a 1:2 ratio] furnished the desired organic polymers (homopolymers and random copolymers) in excellent yields (up to 90 %) and low polydispersities (IPD 1.1-1.3). Remarkably, the in situ-formed polystyril lithium intermediates exhibited a great resistance to hydrolysis in the eutectic mixture 1ChCl/2Gly (up to 1.5 h), hinting at an unexpected high stability of these otherwise highly reactive organolithium species in these unconventional reaction media. This unique stability can be exploited to create well defined block-copolymers.

Direct Functionalization of Poly(spirophosphazene)s via the Regioselective Lithiation of the Aromatic Rings Using a Cooperative Superbase.

The direct chemical functionalization of poly(spirophosphazene) [NP(O2 C12 H8 )]n (1) can be performed by the lithiation of the aromatic rings at low temperature using Schlosser's base (Lit Bu/KOt Bu or "superbase"), and the subsequent reaction with various electrophiles such as ClSiMe3 , ClPPh2 , or MeOB(O2 C6 H12 ) (MeOBpin). The functionalized polymers, isolated in very high yields (>90%) and without degradation of the polymeric chains, have an average degree of substitution per repeat unit ranging from 0.3 (random copolymers) to a maximum of 1.0, which corresponds to the homopolymers [NP(O2 C12 H7 FG)]n (FG (functional group) =SiMe3 , PPh2 , and Bpin). NMR studies, including bidimensional high temperature experiments on silylated and deuterated polymers, show that the substitution is regioselectively occurring at the C3 carbon of the aromatic rings due to the coordination of the lithium cations to the nitrogen of the polyphosphazene chain. The introduction of functional groups on the aromatic rings leads to significant changes in the solubility (silylated polymers), Tg , and electronic properties of the material, showing how the change of substituents in the aromatic rings can lead to polyphosphazenes with properties markedly different from those of the precursor polymer.

Formation and Reversible Morphological Transition of Bicontinuous Nanospheres and Toroidal Micelles by the Self-Assembly of a Crystalline-b-Coil Diblock Copolymer.

We herein report the formation of two complex nanostructures, toroidal micelles and bicontinuous nanospheres, by the self-assembly of the single structurally simple crystalline-b-coil diblock copolymer poly[bis(trifluoroethoxy)phosphazene]-b-poly(styrene), PTFEP-b-PS, in one solvent (THF) and without additives. The nature of these nanostructures in solution was confirmed by DLS and cryo-TEM experiments. The two morphologies are related by means of a new type of reversible morphological evolution, bicontinuous-to-toroidal, triggered by changes in the polymer concentration. WAXS experiments showed that the degree of crystallinity of the PTFEP chains located at the core of the toroids was higher than that in the bicontinuous nanospheres, thus indicating that the final morphology of the aggregates is mostly determined by the ordering of the PTFEP core-forming blocks.

Porous films by the self-assembly of inorganic rod-b-coil block copolymers: mechanistic insights into the vesicle-to-pore morphological evolution.

The self-assembly in thin films of polyphosphazene block copolymers [N = P(O2C12H8)]n-b-[N = PMePh]m (O2C12H8 = 2,2'-dioxy-1,1'-biphenyl; : n = 50, m = 35; : n = 20, m = 70, and : n = 245, m = 60), having different volume fractions of the rigid [N = P(O2C12H8)]n block, has been studied. BCP spontaneously self-assembled into well-defined round-shaped macroporous films, observing also, as a minor morphology, spherical vesicles in regions where the film was not formed. A detailed study by SEM, TEM and AFM of the structure of the vesicles, the morphology of the pores (inverted mushroom-shaped), and the behaviour of the copolymers with shorter () and longer () [N = P(O2C12H8)]n rigid blocks provided sufficient experimental evidence to propose a vesicle-to-pore morphological evolution as the most likely mechanism to explain the pore formation during the self-assembly of . Moreover, by changing the volume fraction of the rigid block and the speed of solvent evaporation, it was possible to vary the pore morphology (and their diameter) from isolated regular groups to 3D interconnected pore networks.

Reversible Morphological Evolution of Responsive Giant Vesicles to Nanospheres by the Self-Assembly of Crystalline-b-Coil Polyphosphazene Block Copolymers.

The preparation of long-term-stable giant unilamellar vesicles (GUVs, diameter ≥ 1000 nm) and large vesicles (diameter ≥ 500 nm) by self-assembly in THF of the crystalline-b-coil polyphosphazene block copolymers [N=P(OCH2CF3)2 ]n-b-[N=PMePh]m (4 a: n=30, m=20; 4 b: n=90, m=20; 4 c: n=200, m=85), which combine crystalline [N=P(OCH2CF3)2] and amorphous [N=PMePh] blocks, both of which are flexible, is reported. SEM, TEM, and wide-angle X-ray scattering experiments demonstrated that the stability of these GUVs is induced by crystallization of the [N=P(OCH2CF3)2] blocks at the capsule wall of the GUVS, with the [N=PMePh] blocks at the corona. Higher degrees of crystallinity of the capsule wall are found in the bigger vesicles, which suggests that the crystallinity of the [N=P(OCH2CF3)2] block facilitates the formation of large vesicles. The GUVs are responsive to strong acids (HOTf) and, after selective protonation of the [N=PMePh] block, they undergo a morphological evolution to smaller spherical micelles in which the core and corona roles have been inverted. This morphological evolution is totally reversible by neutralization with a base (NEt3), which regenerates the original GUVs. The monitoring of this process by dynamic light scattering allowed a mechanism to to be proposed for this reversible morphological evolution in which the block copolymer 4 a and its protonated form 4 a(+) are intermediates. This opens a route to the design of reversibly responsive polymeric systems in organic solvents. This is the first reversibly responsive vesicle system to operate in organic media.

Polyphosphazenes for the Stille reaction: a new type of recyclable stannyl reagent.

A random phosphazene copolymer {[N = P((CH2)7-Br)Ph]0.5[N = PMePh]0.5}n (2) and a block copolyphosphazene {[N = P((CH2)7-Br)Ph]0.5[N = PMePh]0.5}45-b-[N = P(O2C12H8)]55 (5), having a branch with two randomly distributed units, have been synthesized and used as precursors for the stannyl derivatives {[N = P((CH2)7-SnBu2An)Ph]0.5[N = PMePh]0.5}n (3) and {[N = P((CH2)7-SnBu2An)Ph]0.5[N = PMePh]0.5}45-b-[N = P(O2C12H8)]55 (6, An = p-MeOC6H4). Polymers 3 and 6 were tested as recyclable tin reagents in the Stille cross-coupling reaction with ArI, using various Pd catalysts and different experimental conditions. Polymer 6 can be recycled without a significant release of tin, but its efficiency decreased after three consecutive cycles. This effect was explained by studying the self-assembly of the polymer under the same conditions used for the catalytic experiments, which evidenced the progressive coalescence of the polymeric vesicles (polymersomes) leading to stable and bigger core-shell aggregates by the attraction of the [N = P(O2C12H8)] rich membranes, thus decreasing the accessibility of the tin active centers.

Tuning the Chirality of Block Copolymers: From Twisted Morphologies to Nanospheres by Self-Assembly.

New advances into the chirality effect in the self-assembly of block copolymers (BCPs) have been achieved by tuning the helicity of the chiral-core-forming blocks. The chiral BCPs {[N=P(R)-O2C20H12](200-x)[N=P(OC5H4N)2](x)}-b-[N=PMePh]50 ((R)-O2C20H12 = (R)-1,1'-binaphthyl-2,2'-dioxy, OC5H4N = 4-pyridinoxy (OPy); x = 10, 30, 60, 100 for 3 a-d, respectively), in which the [N=P(OPy)2] units are randomly distributed within the chiral block, have been synthesised. The chiroptical properties of the BCPs ([α]D vs. T and CD) demonstrated that the helicity of the BCP chains may be simply controlled by the relative proportion of the chiral and achiral (i.e., [N=P(R)-O2C20H12] and [N=P(OPy)2], respectively) units. Thus, although 3 a only contained only 5% [N=P(OPy)2] units and exhibited a preferential helical sense, 3 d with 50% of this unit adopted non-preferred helical conformations. This gradual variation of the helicity allowed us to examine the chirality effect on the self-assembly of chiral and helical BCPs (i.e., 3 a-c) and chiral but non-helical BCPs (i.e., 3 d). The very significant influence of the helicity on the self-assembly of these materials resulted in a variety of morphologies that extend from helical nanostructures to pearl-necklace aggregates and nanospheres (i.e., 3 b and 3 d, respectively). We also demonstrate that the presence of pyridine moieties in BCPs 3 a-d allows specific decoration with gold nanoparticles.

Gold-decorated chiral macroporous films by the self-assembly of functionalised block copolymers.

We describe a new and very versatile method to place chosen chemical functionalities at the edge of the pores of macroporous materials. The method is based on the synthesis and self-assembly of inorganic block copolymers (BCPs) having chiral rigid segments bearing controllable quantities of randomly distributed functional groups. The synthesis of a series of optically active block copolyphosphazenes (PP) with the general formula [N=P(R-O2C20H12)(0.9)(FG)(0.2)]n-b-[N=PMePh]m (FG=-OC5H4N (6), -NC4H8S (7), and -NC4H8O (8)), was accomplished by the sequential living cationic polycondensation of N-silylphosphoranimines, using the mono-end-capped initiator [Ph3P=N=PCl3][Cl] (3). The self-assembly of the phosphazene BCPs 6-8 led to chiral porous films. The functionality present on those polymers affected their self-assembly behaviour resulting in the formation of pores of different diameters (D(n)=111 (6), 53 (7) and 77 nm (8)). The specific functionalisation of the pores was proven by decorating the films with gold nanoparticles (AuNPs). Thus, the BCPs 6 and 7, having pyridine and thiomorpholine groups, respectively, were treated with HAuCl4, followed by reduction with NaBH4, yielding a new type of block copolyphosphazenes, which self-assembled into chiral porous films specifically decorated with AuNPs at the edge of the pores.

Twisted morphologies and novel chiral macroporous films from the self-assembly of optically active helical polyphosphazene block copolymers.

A series of optically active helical polyphosphazene block copolymers of general formula R-[N=P(O2C20H12)]n-b-[N=PMePh]m (R-7 a-c) was synthesized and characterized. The polymers were prepared by sequential living cationic polycondensation of N-silylphosphoranimines using the mono-end-capped initiator [Ph3 P=N=PCl3][PCl6] (5) and exhibit a low polydispersity index (ca. 1.3). The temperature dependence of the specific optical activity ([α]D) of R-7 a,b relative to that for the homopolymers R-[N=P(O2C20H12)]n (R-8 a) and the R/S analogues (R/S-7 a,b), revealed that the binaphthoxy-phosphazene segments induce a preferential helical conformation in the [N=PMePh] blocks through a "sergeant-and-soldiers" mechanism, an effect that is unprecedented in polyphosphazenes. The self-assembly of drop-cast thin films of the chiral block copolymer R-7 b (bearing a long chiral and rigid R-[N=P(O2C20H12)] segment) evidenced a transfer of helicity mechanism, leading to the formation of twisted morphologies (twisted "pearl necklace"), not observed in the nonchiral R/S-7 b. The chiral R-7 a and the nonchiral R/S-7 a, self-assemble by a nondirected morphology reconstruction process into regular-shaped macroporous films with chiral-rich areas close to edge of the pore. This is the first nontemplate self-assembly route to chiral macroporous polymeric films with pore size larger than 50 nm. The solvent annealing (THF) of these films leads to the formation of regular spherical nanostructures (ca. 50 nm), a rare example of nanospheres exclusively formed by synthetic helical polymers.

A cooperative role for the counteranion in the PCl5-initiated living, cationic chain growth polycondensation of the phosphoranimine Cl3P═NSiMe3.

The counteranion associated with the cationic initiator [Cl(3)P═N═PCl(3)](+) ([4](+)) generated during the PCl(5)-initiated living, cationic chain growth polycondensation of the N-silylphosphoranimine Cl(3)P═NSiMe(3) (3) to give poly(dichlorophosphazene), [N═PCl(2)](n) (2), has been found to have a dramatic effect on the polymerization. When the counteranion of [4](+) was changed from PCl(6)(-) or Cl(-) to the weakly coordinating anions [BAr*(F)(4)](-) and [BAr(F)(4)](-) (Ar*(F) = 3,5-{CF(3)}(2)C(6)H(3), Ar(F) = C(6)F(5)) instead of the polymerization of 3 being complete in 4-6 h, no reaction was observed after 24 h. Remarkably, the polymerization of 3 may be initiated by Cl(-) anions even in the absence of an active cation such as [4](+). However, in the presence of [4](+), the reaction proceeded significantly faster and allowed for molecular weight control. These results reveal that the currently accepted mechanism for the PCl(5)-initiated living polymerization of 3 needs to be revised to reflect the key role of the counteranion present.

Functionalization of poly(ferrocenyldimethylsilane) via lithiation of the cyclopentadienyl rings.

The metallation of the cyclopentadienyl (Cp) ligands of poly(ferrocenyldimethylsilane) (PFDMS) can be performed by reaction with the Schlosser's base pair t-BuLi/KOt-Bu in THF. Subsequent treatment with a series of electrophiles affords a range of Cp-substituted polymers with up to an average of 1.8 new substituents per repeating unit. NMR studies on polymers containing trimethylsilyl groups and deuterium on the Cp rings are indicative of high regioselectivity with selective metallation at the ß-carbon.

Polymeric materials based on main group elements: the recent development of ambient temperature and controlled routes to polyphosphazenes.

This Perspective discusses the development of new routes to polyphosphazenes, [R(2)P[double bond, length as m-dash]N](n), that occur at ambient temperature and, in some cases, allow molecular weight control and access to narrow molecular weight distributions and block copolymers. For example, the room temperature silyl-carborane initiated ring-opening polymerisation of (NPCl(2))(3) is described together with chain growth condensation polymerisations of phosphoranimines Cl(3)P[double bond, length as m-dash]NSiMe(3) and BrMePhP[double bond, length as m-dash]NSiMe(3). Recent works on donor-stabilised cationic phosphoranimines are also discussed.