Chiral information harvesting in helical poly(acetylene) derivatives using oligo(p-phenyleneethynylene)s as spacers

A chiral harvesting transmission mechanism is described in poly(acetylene)s bearing oligo(p-phenyleneethynylene)s (OPEs) used as rigid achiral spacers and derivatized with chiral pendant groups. The chiral moieties induce a positive or negative tilting degree in the stacking of OPE units along the polymer structure, which is further harvested by the polyene backbone adopting either a P or M helix.

A chiral harvesting transmission mechanism is described in poly(acetylene)s bearing oligo(p-phenyleneethynylene)s (OPEs) used as rigid achiral spacers and derivatized with chiral pendant groups.

During the last years, dynamic helical polymers have attracted the attention of the scientific community due to the possibility of tuning the helical sense and/or the elongation of the helical structure by using external stimuli.^1–14In the case of a chiral dynamic helical polymer, modifications in its structure—helical sense enhancement or helix inversion—arise from conformational changes induced at its chiral pendants—usually, with just one stereocenter—, by stimuli such as variations in solvent polarity or temperature, the addition of certain ions, and so on (Fig. 1a).¹⁵ On the other hand, if a helical polymer is achiral (i.e., bearing achiral pendants), the chiral amplification phenomena can emerge from interactions between the polymer and external chiral molecules.¹⁶ In both the above cases, the changes produced in the helical structures are related to the spatial dispositions adopted by the substituents or associated species at the pendant groups.^17–19Open in a separate windowFig. 1Several scenarios depicting conceptual representations of the transmission of chiral information. (a) Helical switch via chiral tele-induction. (b) Effect of distance on chiral tele-induction from multichiral pendants. (c) Helicity controlled by the conformational composition of achiral spacers.A step forward in the helical sense control of poly(phenylacetylene)s (PPA)s is to study different mechanisms of transmission of chiral information from the pendant to the polyene backbone by introducing achiral spacers. The goal is to demonstrate how far it is possible to place the chiral center and still have an effective chiral induction on the polyene backbone. Therefore, transmission of the chiral information from a remote position can occur through space, thus overpassing the distance generated by the spacer—tele-induction—(Fig. 1b),^20–28 or through the achiral spacer itself, producing in it a preferred structure, such as a helical structure and where the orientation of the achiral helix is further transmitted to the polyene backbone—conformational switch—(Fig. 1c).^29–31For the first mechanism—chiral tele-induction—, both flexible and rigid spacers have been designed.^20–28 In all cases, supramolecular interactions, such as H bonding or π–π stacking, generate organized structures. As a result, the chiral center is located into a specific orientation, producing an effective helical induction. Additionally, those studies allow evaluating how distances and sizes have an effect on this phenomenon.In the second strategy, the helix induction is transmitted through conformational changes along an achiral spacer which is harvested by the polyene. For instance, an achiral peptide or an achiral polymeric helix derivatized at one end with a chiral residue and linked to the polymer main chain at the other end. In such cases, changes in the absolute configuration or even just a conformational change at the chiral center can induce an opposite helical structure into the achiral spacer, which in turn will be harvested by the polymer main chain (Fig. 1c).^29–31Herein we will demonstrate another remote chiral induction mechanism based on a different chiral harvesting process. In this case, the chiral center does not produce a conformational change at the achiral spacer, but affects its array within the helical scaffold. Thus, to perform these studies we decided to introduce the use of oligo(p-phenyleneethynylene)s (m = 1, 2, 3) (OPEs) as rigid spacers to separate the distant chiral center from the polyene backbone. These OPE units have been used in the formation of benzene-1,3,5-tricarboxamide (BTA) based supramolecular helical polymers, demonstrating their ability to stack with a certain tilting degree commanded by the chiral center.^32–34Hence, in our design, the chiral moiety will determine the supramolecular chiral orientation of the OPE groups used as spacers, which is further harvested by the polyene backbone. The overall process yields a helix with a preferred screw sense (Fig. 2).Open in a separate windowFig. 2Conceptual side view and top view of the chiral information transmission mechanism from stereocenters at the far end of oligo(p-phenyleneethynylene) spacers to the polyene backbone via chiral harvesting.To perform these studies, we used as model compounds two PPAs—poly-(R)-1 and poly-(S)-1—derived from the 4-ethynylanilide of (S)- and (R)-α-methoxy-α-phenylacetic acid (MPA, m-(S/R)-1), whose helical structures and dynamic behaviors have been deeply studied by our group—poly-(R)-1 and poly-(S)-1—(Fig. 3).^35–46 By using these polymers as reference materials, four novel PPAs were designed introducing two OPE spacers—4-[(p-phenyleneethynylene)_n]ethynylanilide (n = 1, 2)—between the phenyl acetylene group and the (S)- or (R)-α-methoxy-α-phenylacetic acid (MPA) chiral group. Thus, monomers m-(S)- and m-(R)-2 and m-(S)- and m-(R)-3 (Fig. 3a) were prepared and submitted to polymerization by using a Rh(i) catalyst poly-(S)- and poly-(R)-2 and poly-(S)- and poly-(R)-3 (Fig. 3b) were obtained in high yield and showed Raman spectra characteristic of cis polyene backbones (see Fig. S11 and S12^†).Open in a separate windowFig. 3(a) Monomers and (b) polymers synthetized in this study.X-ray structures of the monomers show a preferred antiperiplanar (ap) orientation between the carbonyl and methoxy groups (O C–C–OMe) for m-(R)-2 and m-(S)-3, whereas in the case of m-(S)-1 a synperiplanar (sp) geometry is favoured (Fig. 4a).³⁵ In complementary studies, CD spectra of monomers m-(S)-[1–3] in CHCl₃ show negative Cotton effects, indicative of major ap conformations in solution (Fig. 4b),³⁵ further corroborated by theoretical calculations (see Fig. S10^†). Interestingly, the maximums of the Cotton effects in CD undergo a bathochromic shift—from 266 nm in m-1 to 327 nm in m-3—due to a larger conjugation of the π electrons (from the anilide to the alkyne group) when the length of the spacer increases (Fig. 4b).Open in a separate windowFig. 4(a) X-ray structures of m-(S)-1, m-(R)-2 and m-(S)-3. (b) CD traces of m-(S)- and m-(R)-1; m-(S)- and m-(R)-2; m-(S)- and m-(R)-3 in CHCl₃ (0.1 mg mL⁻¹). (c) CD spectra for poly-(S)- and poly-(R)-1 in CHCl₃ (0.1 mg mL⁻¹); poly-(S)- and poly-(R)-2 in DMSO (0.1 mg mL⁻¹); poly-(S)- and poly-(R)-3 in DMSO (0.1 mg mL⁻¹).CD studies of the polymer series bearing OPE spacers—poly-(R)- and poly-(S)-[2–3]—in different solvents show the formation of a PPA helical structure with a preferred helical sense, while the parent polymer, poly-1, devoid of the OPE unit, has a poor CD. This is a very interesting phenomena that indicates that the OPE spacers work as transmitters of the chiral information from remote chiral centers to the polyene backbone—placed at 1.7 nm for poly-2 and at 2.4 nm for poly-3—(Fig. 4a). These large distances between the chiral center and the polymer main chain mean that other mechanisms of chiral induction, such as chiral tele-induction effect, should be almost null in these cases.In these two polymers (poly-2 and poly-3), the chiral information transmission mechanism must occur in different sequential steps. First, the chiral centers possessing a major (ap) conformation induce a certain tilting degree (θ) in the achiral spacer array. This step resembles the helical induction mechanism found in supramolecular helical polymers bearing OPE units.^32–34 Next, the chiral array induced in the OPE units is harvested by the polyene backbone, resulting in an effective P or M helix induction (Fig. 2).^34,47Additional structural studies were carried out in poly-(S)-2 and poly-(S)-3 to obtain an approximated secondary structure of these polymers and determine their dynamic behaviour.From literature it is known that the conformational equilibrium of poly-1 can be altered in solution by the presence of metal ions. The addition of monovalent ions (e.g., Li⁺) stabilizes the ap conformer at the pendant group by cation–π interactions, while divalent ions (e.g., Ca²⁺) stabilize the sp conformations by chelation with the methoxy and carbonyl groups.^36,38,39,43 As a result, both the P or M helical senses can be selectively induced in poly-1 by the action of metal ions.Therefore, we decided to add different perchlorates of monovalent and divalent metal ions to solutions of poly-(S)-2 and poly-(S)-3 with the aim of determining the conformational composition at the pendant groups. Thus, when monovalent metal ions (Li⁺, Ag⁺ and Na⁺) are added to a chloroform solution of poly-(S)-2, a chiral enhancement is observed (Fig. 5d for Li⁺ and Fig. S16^† for Na⁺ and Ag⁺). IR and ⁷Li-NMR studies show that those ions stabilize the ap conformer at the pendant group in a similar fashion to poly-1, this is by coordination to the carbonyl group of the MPA (Fig. 5g) and the presence of a cation–π interaction with the aryl ring of the chiral (|Δδ| ⁷Li ca., 3.75 ppm) (Fig. 5f and ESI^†). Therefore, addition of Li⁺ produces a larger number of pendant groups with ap conformation among poly-2, which triggers a chiral enhancement effect through a cooperative process.Open in a separate windowFig. 5(a) Conceptual representation of the chiral information harvesting and top view of the 3D model for poly-(S)-2. (b) CD spectra of poly-(S)-2 (0.2 mg mL⁻¹) in DMSO vs. calculated ECD spectra. Full width at half-maximum (FWHM) equals 20 nm. (c) Low-resolution AFM image from a poly-(S)-2 monolayer and profile depicting the chain separation of the yellow highlighted area in the AFM image. (d) CD spectra showing the chiral enhancement after the addition of Li⁺ (50 mg mL⁻¹, THF) to a poly-(S)-2 solution (0.1 mg mL⁻¹, THF). (e) CD trace of poly-(S)-2 before and after the addition of a Ca²⁺ solution (50 mg mL⁻¹, THF). (f) ⁷Li-NMR spectra substantiating the cation–π interaction. (g) IR shifts observed for carbonyl and methoxy groups after the addition of LiClO₄ and Ca(ClO₄)₂ (50 mg mL⁻¹, THF) to a poly-(S)-2 solution (3 mg mL⁻¹, CHCl₃). The coordination modes of the MPA moiety with Li⁺ and Ca²⁺ are shown vertically in the middle of the figure.On the contrary, the addition of perchlorates of divalent metal ions, such as Ca²⁺and Zn²⁺, produced an inversion of the third Cotton band—310 nm—associated to the MPA moiety and the disappearance of both first and second Cotton effects (Fig. 5e for Ca²⁺ and Fig. S17^† for Zn²⁺). This is a very interesting outcome because, although the conformational equilibrium at the MPA group changes from ap to sp after the addition of Ca²⁺, the number of pendant groups with sp conformation do not reach the number needed to trigger the helix inversion process and in fact, a mixture of P and M helices at the polyene backbone is obtained.The helical structures adopted by both polymer systems, PPAs (poly-1) and poly[oligo(p-phenyleneethynylene)phenylacetylene]s (POPEPAs) (poly-2 and poly-3), are defined by two coaxial helices, one formed by the polyene backbone (internal helix, CD active) and the other constituted by the pendants (external helix, observed by AFM).These two helices can rotate in either the same or the opposite sense, depending on the dihedral angle between conjugated double bonds. Thus, internal and external helices rotate in the same direction in cis-cisoidal polymers, while they rotate in opposite directions in cis-transoidal ones.^14,42,48,49In order to find out an approximated helical structure for poly-(S)-2, DSC studies were performed. The thermogram shows a compressed cis-cisoidal polyene skeleton (see Fig. S13a^†), similar to the one obtained for poly-1.⁴² Moreover, AFM studies on a 2D crystal of poly-(S)-2 did not produce high-resolution AFM images, although some parameters such as helical pitch (c.a., 2.8 nm) and packing distance between helices of (c.a., 6 nm) could be extracted from the well-ordered monolayer analyzed (Fig. 5c).Previous structural studies in PPAs found that it is possible to correlate the internal helical sense with the Cotton band associated to the polyene backbone—CD (+), P_int; CD (−), M_int—.^50,51 Herein, the positive Cotton effect observed for the polyene backbone [CD_{365 nm} = (+)] in poly-(S)-2 is indicative of a P orientation of the internal helix, which correlates with a P orientation of the external helix in a cis-cisoidal polyene scaffold. To summarize, DSC, AFM and CD studies agree that poly-(S)-2 is made up of a cis-cisoidal framework with P_int and P_ext helicities (Fig. 5a).Computational studies [TD-DFT(CAM-B3LYP)/3-21G] were carried out on a P helix of an n = 9 oligomer of poly-(S)-2, possessing a cis-cisoidal polyene skeleton (ω₁ = +50°, ω₃ = −40°) and an antiperiplanar orientation of the carbonyl and methoxy groups at the pendants. The theoretical ECD spectrum obtained from these studies (Fig. 5b and see ESI^† for additional information) is in good agreement with the experimental one, indicating that our model structure is a good approximation of the helical structure adopted by poly-(S)-2.Next, a similar set of DSC and AFM studies were carried out for poly-(S)-3, that bears an OPE spacer with n = 2. The data showed that this polymer presents a compressed cis-cisoidal polyene skeleton, similar to those obtained for poly-1 and poly-2 (see Fig. S13b^†), with a helical pitch of 3.8 nm and a P_ext helical sense (Fig. 6a and c).Open in a separate windowFig. 6(a) Conceptual representation of the chiral information harvesting and top view of the 3D model for poly-(S)-3. (b) CD spectrum of poly-(S)-3 in THF (0.2 mg mL⁻¹) and comparison to the calculated ECD spectra. Full width at half-maximum (FWHM) equals 20 nm. (c) AFM image obtained from a poly-(S)-3 monolayer. (d) CD traces for poly-(S)-3 in THF polymerized at different temperatures.UV studies indicate that, in poly-(S)-3, the polyene backbone absorbs at ca. 380 nm, coincident with the first Cotton effect, that is positive (see Fig. S15b^†). Therefore, it reveals that poly-(S)-3 adopts a P_int helicity (Fig. 6b). Thus, as expected for cis-cisoidal scaffolds, the orientations of the two coaxial helices are coincident.Computational studies [TD-DFT(CAM-B3LYP)/3-21G] were carried out on a P helix of an n = 9 oligomer of poly-(S)-3, possessing a cis-cisoidal polyene skeleton (ω₁ = +63°, ω₃ = −40°) and an antiperiplanar orientation of the carbonyl and methoxy groups at the pendants. The theoretical results (Fig. 6b and see ESI^† for additional information) match with the experimental data, indicating that our model structure is a good approximation to the helical structure adopted by poly-(S)-3.Finally, the stimuli response properties of poly-(S)-3 were explored by CD. These experiments revealed that the addition of monovalent or divalent metal ions to a chloroform solution of poly-(S)-3 does not produce any significant effect in the structural equilibrium of this polymer (see Fig. S18^†). This fact, in addition to the previous results obtained from the interaction of poly-(S)-2 with divalent metal ions, corroborates the decrease of the dynamic character of helical PPAs when large OPEs are used as spacers.The poor dynamic behaviour was further demonstrated by polymerizing m-(S)-3 at a lower temperature (0 °C) (Fig. 6d). In this case, the region around 240–350 nm remains unaffected, indicating that the pendant is ordered in a similar manner in both batches of polymers, regardless of the temperature at which they were synthesized (20 °C and 0 °C). Interestingly, the magnitude of the first Cotton band is duplicated when the polymer is obtained at low temperature due to a stronger helical sense induction at the polyene backbone. This result indicates that a preorganization process may occur during polymerization, affecting the screw sense excess of the PPA.In conclusion, a novel chiral harvesting transmission mechanism has been described in poly(acetylene)s bearing oligo(p-phenylenethynylene)s as rigid spacers that place the chiral pendant group away from the polyene backbone, at a distance around ca. 1.7 nm for poly-2, and 2.4 nm for poly-3. Hence, the disposition of the chiral moiety affects the stacking of the OPE units within the helical structure, inducing a specific positive or negative tilting degree, which is further harvested by the polyene backbone inducing either a P or M internal helix.We believe that these results open new horizons in the development of novel helical structures by combining information from the helical polymers and supramolecular helical polymers fields, which leads to the formation of novel materials with applications in important fields such as asymmetric synthesis, chiral recognition or chiral stationary phases among others.     

Photo-induced copper-catalyzed alkynylation and amination of remote unactivated C(sp3)-H bonds

A method for remote radical C–H alkynylation and amination of diverse aliphatic alcohols has been developed. The reaction features a copper nucleophile complex formed in situ as a photocatalyst, which reduces the silicon-tethered aliphatic iodide to an alkyl radical to initiate 1,n-hydrogen atom transfer. Unactivated secondary and tertiary C–H bonds at β, γ, and δ positions can be functionalized in a predictable manner.

Remote C−H alkynylation and amination of aliphatic alcohols.     

C4-arylation and domino C4-arylation/3,2-carbonyl migration of indoles by tuning Pd catalytic modes: Pd(i)–Pd(ii) catalysis vs. Pd(ii) catalysis

Efficient C4-arylation and domino C4-arylation/3,2-carbonyl migration of indoles have been developed. The former route enables C4-arylation in a highly efficient and mild manner and the latter route provides an alternative straightforward protocol for synthesis of C2/C4 disubstituted indoles. The mechanism studies imply that the different reaction pathways were tuned by the distinct acid additives, which led to either the Pd(i)–Pd(ii) pathway or Pd(ii) catalysis.

C4-arylation via Pd(i)–Pd(ii) catalysis and domino C4-arylation/3,2-carbonyl migration of indoles via Pd(ii) catalysis tuning by acids have been developed.     

Boosting homogeneous chemoselective hydrogenation of olefins mediated by a bis(silylenyl)terphenyl-nickel(0) pre-catalyst

The isolable chelating bis(N-heterocyclic silylenyl)-substituted terphenyl ligand [Si^II(Terp)Si^II] as well as its bis(phosphine) analogue [P^III(Terp)P^III] have been synthesised and fully characterised. Their reaction with Ni(cod)₂ (cod = cycloocta-1,5-diene) affords the corresponding 16 VE nickel(0) complexes with an intramolecular η²-arene coordination of Ni, [E(Terp)E]Ni(η²-arene) (E = P^III, Si^II; arene = phenylene spacer). Due to a strong cooperativity of the Si and Ni sites in H₂ activation and H atom transfer, [Si^II(Terp)Si^II]Ni(η²-arene) mediates very effectively and chemoselectively the homogeneously catalysed hydrogenation of olefins bearing functional groups at 1 bar H₂ pressure and room temperature; in contrast, the bis(phosphine) analogous complex shows only poor activity. Catalytic and stoichiometric experiments revealed the important role of the η²-coordination of the Ni(0) site by the intramolecular phenylene with respect to the hydrogenation activity of [Si^II(Terp)Si^II]Ni(η²-arene). The mechanism has been established by kinetic measurements, including kinetic isotope effect (KIE) and Hammet-plot correlation. With this system, the currently highest performance of a homogeneous nickel-based hydrogenation catalyst of olefins (TON = 9800, TOF = 6800 h⁻¹) could be realised.

The isolable chelating bis(N-heterocyclic silylenyl)-substituted terphenyl ligand [Si^II(Terp)Si^II] as well as its bis(phosphine) analogue [P^III(Terp)P^III] have been synthesised and fully characterised.     

Preparation of α-amino acids via Ni-catalyzed reductive vinylation and arylation of α-pivaloyloxy glycine

This work emphasizes easy access to α-vinyl and aryl amino acids via Ni-catalyzed cross-electrophile coupling of bench-stable N-carbonyl-protected α-pivaloyloxy glycine with vinyl/aryl halides and triflates. The protocol permits the synthesis of α-amino acids bearing hindered branched vinyl groups, which remains a challenge using the current methods. On the basis of experimental and DFT studies, simultaneous addition of glycine α-carbon (Gly) radicals to Ni(0) and Ar–Ni(ii) may occur, with the former being more favored where oxidative addition of a C(sp²) electrophile to the resultant Gly–Ni(i) intermediate gives a key Gly–Ni(iii)–Ar intermediate. The auxiliary chelation of the N-carbonyl oxygen to the Ni center appears to be crucial to stabilize the Gly–Ni(i) intermediate.

We have developed Ni-catalyzed reductive coupling of N-carbonyl protected α-pivaloyloxy glycine with Csp²-electrophiles that enabled facile preparation of α-amino acids, including those bearing hindered branched vinyl groups.     

Enantioselective total synthesis of (−)-myrifabral A and B

A catalytic enantioselective approach to the Myrioneuron alkaloids (−)-myrifabral A and (−)-myrifabral B is described. The synthesis was enabled by a palladium-catalyzed enantioselective allylic alkylation, that generates the C(10) all-carbon quaternary center. A key N-acyl iminium ion cyclization forged the cyclohexane fused tricyclic core, while vinyl boronate cross metathesis and oxidation afforded the lactol ring of (−)-myrifabral A. Adaptation of previously reported conditions allowed for the conversion of (−)-myrifabral A to (−)-myrifabral B.

A catalytic enantioselective approach to the Myrioneuron alkaloids (−)-myrifabral A and (−)-myrifabral B is described.     

A palladium-catalyzed C–H functionalization route to ketones via the oxidative coupling of arenes with carbon monoxide

We describe the development of a new palladium-catalyzed method to generate ketones via the oxidative coupling of two arenes and CO. This transformation is catalyzed by simple palladium salts, and is postulated to proceed via the conversion of arenes into high energy aroyl triflate electrophiles. Exploiting the latter can also allow the synthesis of unsymmetrical ketones from two different arenes.

A palladium catalyzed route to prepare aryl ketones from their two fundamental building blocks, two arenes and carbon monoxide, is described.     

Triple the fun: tris(ferrocenyl)arene-based gold(i) complexes for redox-switchable catalysis

The modular syntheses of C₃-symmetric tris(ferrocenyl)arene-based tris-phosphanes and their homotrinuclear gold(i) complexes are reported. Choosing the arene core allows fine-tuning of the exact oxidation potentials and thus tailoring of the electrochemical response. The tris[chloridogold(i)] complexes were investigated in the catalytic ring-closing isomerisation of N-(2-propyn-1-yl)benzamide, showing cooperative behaviour vs. a mononuclear chloridogold(i) complex. Adding one, two, or three equivalents of 1,1′-diacetylferrocenium[tetrakis(perfluoro-tert-butoxy)aluminate] as an oxidant during the catalytic reaction (in situ) resulted in a distinct, stepwise influence on the resulting catalytic rates. Isolation of the oxidised species is possible, and using them as (pre-)catalysts (ex situ oxidation) confirmed the activity trend. Proving the intactness of the P–Au–Cl motif during oxidation, the tri-oxidised benzene-based complex has been structurally characterised.

Trinuclear gold(i) complexes of C₃-symmetric tris(ferrocenyl)arene-based tris-phosphanes with four accessible oxidation states catalyse the ring-closing isomerisation of N-(2-propyn-1-yl)benzamide with different rates depending on their redox state.     

Catalytic asymmetric synthesis of 3,2′-pyrrolinyl spirooxindoles via conjugate addition/Schmidt-type rearrangement of vinyl azides and (E)-alkenyloxindoles

A catalytic asymmetric conjugate addition/Schmidt-type rearrangement of vinyl azides and (E)-alkenyloxindoles was realized. It afforded a variety of optically active 3,2′-pyrrolinyl spirooxindoles with high yields (up to 98%), and excellent diastereo- and enantioselectivities (up to 98% ee, >19 : 1 dr), even at the gram-scale in the presence of a chiral N,N′-dioxide–nickel(ii) complex. In addition, a possible catalytic cycle and transition state model were proposed to rationalize the stereoselectivity.

Lewis acid catalyzed asymmetric synthesis of 3,2′-pyrrolinyl spirooxindole skeletons via conjugate addition/Schmidt-type rearrangement of vinyl azides and (E)-alkenyloxindoles.     

Chiral N,N′-dioxide/Mg(OTf)2 complex-catalyzed asymmetric [2,3]-rearrangement of in situ generated ammonium salts

Catalytic enantioselective [2,3]-rearrangements of in situ generated ammonium ylides from glycine pyrazoleamides and allyl bromides were achieved by employing a chiral N,N′-dioxide/Mg^II complex as the catalyst. This protocol provided a facile and efficient synthesis route to a series of anti-α-amino acid derivatives in good yields with high stereoselectivities. Moreover, a possible catalytic cycle was proposed to illustrate the reaction process and the origin of stereoselectivity.

The Lewis acid catalyzed asymmetric [2,3]-rearrangement of quaternary ammonium ylides formed in situ from glycine pyrazoleamides and allyl bromides.     

Tandem aza-Heck Suzuki and carbonylation reactions of O-phenyl hydroxamic ethers: complex lactams via carboamination

The palladium-catalysed tandem aza-Heck–Suzuki and aza-Heck–carbonylation reactions of O-phenyl hydroxamic ethers are reported. These formal alkene carboamination reactions provide highly versatile access to wide range complex, stereogenic secondary lactams and exhibit outstanding functional group tolerance and high diastereoselectivity.

The palladium-catalysed tandem aza-Heck–Suzuki and aza-Heck–carbonylation reactions of O-phenyl hydroxamic ethers are reported.     

Cobalt-catalyzed aminocarbonylation of (hetero)aryl halides promoted by visible light

The catalytic aminocarbonylation of (hetero)aryl halides is widely applied in the synthesis of amides but relies heavily on the use of precious metal catalysis. Herein, we report an aminocarbonylation of (hetero)aryl halides using a simple cobalt catalyst under visible light irradiation. The reaction extends to the use of (hetero)aryl chlorides and is successful with a broad range of amine nucleophiles. Mechanistic investigations are consistent with a reaction proceeding via intermolecular charge transfer involving a donor–acceptor complex of the substrate and cobaltate catalyst.

An aminocarbonylation of (hetero)aryl halides using a simple cobalt catalyst under visible light irradiation is presented.     

Total synthesis of (−)-penicimutanin a and related congeners

The first total synthesis of penicimutanin A (1) was achieved within 10 steps (LLS). Key innovations in this synthesis consist of (1) a highly efficient electro-oxidative dearomatization; (2) an unprecedented bisoxirane-directed intermolecular aldol reaction from the sterically hindered face of the ketone and (3) the diastereoselective one-step Meerwein–Eschenmoser–Claisen rearrangement enabling the construction of vicinal quaternary stereocenters. Related family members e.g. penicimutanolone (3) and penicimutatin (5) have also been synthesized alongside, elucidating their absolute configurations, hence the absolute configuration of 1.

The first total synthesis of penicimutanin A (1) was achieved within 10 steps (LLS).     

Rh(iii)-catalyzed tandem annulative redox-neutral arylation/amidation of aromatic tethered alkenes

Transition-metal-catalyzed directed C–H functionalization has emerged as a powerful and straightforward tool to construct C–C bonds and C–N bonds. Among these processes, the intramolecular annulative alkene hydroarylation reaction has received much attention because this intramolecular annulation can produce more complex and high value-added structural motifs found in numerous natural products and bioactive molecules. Despite remarkable progress, these annulative protocols developed to date remain limited to hydroarylation and functionalization of one side of alkenes, thus largely limiting the structural diversity and complexity. Herein, we developed a rhodium(iii)-catalyzed tandem annulative arylation/amidation reaction of aromatic tethered alkenes to deliver a variety of 2,3-dihydro-3-benzofuranmethanamine derivatives bearing an all-carbon quaternary stereo center by employing 3-substituted 1,4,2-dioxazol-5-ones as an amidating reagent to capture the transient C(sp³)–Rh intermediate. Notably, by simply changing the directing group, a second, unsymmetrical ortho C–H amidation/annulation can be achieved to provide tricyclic dihydrofuro[3,2-f]quinazolinones in good yields.

A rhodium(iii)-catalyzed tandem annulative arylation/amidation reaction of aromatic tethered alkenes was developed to deliver a variety of 2,3-dihydro-3-benzofuranmethanamine derivatives.

Transition-metal-catalyzed C–H functionalization for the direct conversion of C–H bonds to C–C bonds and C–N bonds has evolved into a widespread and effective strategy for fine chemical production.¹ Among these processes, the hydroarylation of C–C double bonds via a C–H addition has been well-established and become an effective strategy to access synthetically useful structural motifs.¹ Recently, this alkene hydroarylation reaction has received much attention in an intramolecular fashion² (Scheme 1a) because this intramolecular annulation can produce more complex and high value-added structural motifs found in numerous natural products and bioactive molecules (Fig. 1).³ Despite remarkable progress in this area, most of the annulative protocols developed to date remain limited to one-component intramolecular alkene hydroarylation and functionalization of one side of alkenes. More challenging C–H arylation of intramolecular alkenes followed by a tandem coupling with a different coupling partner have unfortunately proven elusive thus far, thus largely limiting the structural diversity and complexity.Open in a separate windowFig. 1Representative bioactive 2,3-dihydrobenzofurans.Open in a separate windowScheme 1Transition-metal-catalyzed C–H functionalization to construct the C–C and C–N bonds.On the other hand, nitrogen-containing molecules have gained great attention due to their widespread presence in natural products and widespread use in pharmaceutical science.⁴ During the last two decades, transition-metal-catalyzed direct C(sp²)–H amination/amidation assisted by chelating directing group is a well-established strategy.⁵ Recently, several examples of C(sp³)–H amination/amidation have also been reported for the efficient installation of C–N bonds.^6,7 Mechanistically, the reaction is initiated by a chelation-assisted C–H metalation to form a C(sp³)–M species, which is then coupled with amination reagents to construct the C–N bonds.In this context, we wondered if a catalytic annulative C–H arylation of a O-bearing olefin-tethered arenes might be possible, thus leading to a C(sp³)–M intermediate, which upon capture with a amidation reagent to construct a new C–N bond and provide bioactive 2,3-dihydro-3-benzofuranmethanamine derivatives. Inherently, the tandem annulative 1,2-arylation/amidation of alkenes has several challenges. First, the resulting C(alkyl)–M intermediate is liable to undergo protonation to provide the alkene hydroarylation products.^1,2 Moreover, a potential competing β-H elimination of the resulting C(alkyl)–M intermediate also required to be suppressed. In addition, compared with the C(sp²)–M species, the resulting C(alkyl)–M species is relatively unstable and also has a low reactivity.To address these challenges and with our continuing interest in the Rh(iii)-catalyzed C–H functionalization,⁸ we introduced a Weinreb amide as a directing group and 3-substituted 1,4,2-dioxazol-5-ones as the amide sources⁹ to trigger a new tandem annulative 1,2-arylation/amidation of alkenes via a Rh(iii)-catalyzed C–H activation,¹⁰ providing a variety of synthetically challenging 2,3-dihydro-3-benzofuranmethanamine derivatives bearing an all-carbon quaternary stereo center (Scheme 1b). More importantly, through simply changing the directing group, a second, unsymmetrical ortho C–H amidation/annulation could be realized to provide tricyclic dihydrofuro[3,2-f]quinazolinone derivatives. This protocol provides a good complement to previously reported carboamination reactions.¹¹To begin our studies, Weinreb amide 1a was reacted with methyl dioxazolone 3a in the presence of various catalyst and AgSbF₆ at 70 °C in DCE (Table 1, entries 1–4). The use of [Cp*RhCl₂]₂ as the catalyst was found to be crucial to give the desired tandem annulative product 4a, with other catalysts, such as [Ru(p-cymene)Cl₂]₂, [Cp*IrCl₂]₂, and Cp*Co(CO)I₂, resulting in no desired product. Attempt to increase or lower the reaction temperature led to a slightly low yield (entries 5 and 6). Interestingly, when employing a NH–OMe amide 2a as the substrate and using 3 equivalent of 3a, a second, unsymmetrical ortho C–H amidation/annulation was achieved to provide the tricyclic dihydrofuro[3,2-f]quinazolinone 5a in 50% yield (entry 7). A screen of additives (entries 8–10) identified LiOAc as the optimal additive, affording the desired product 5a in 93% yield (entry 10). The Rh(iii) catalyst was found to be crucial for this tandem annulative arylation/amidation reaction, with no reactivity in its absence (entries 11 and 12).Optimization of reaction conditions^a

Stereoretention in styrene heterodimerisation promoted by one-electron oxidants

Radical cations generated from the oxidation of C C π-bonds are synthetically useful reactive intermediates for C–C and C–X bond formation. Radical cation formation, induced by sub-stoichiometric amounts of external oxidant, are important intermediates in the Woodward–Hoffmann thermally disallowed [2 + 2] cycloaddition of electron-rich alkenes. Using density functional theory (DFT), we report the detailed mechanisms underlying the intermolecular heterodimerisation of anethole and β-methylstyrene to give unsymmetrical, tetra-substituted cyclobutanes. Reactions between trans-alkenes favour the all-trans adduct, resulting from a kinetic preference for anti-addition reinforced by reversibility at ambient temperatures since this is also the thermodynamic product; on the other hand, reactions between a trans-alkene and a cis-alkene favour syn-addition, while exocyclic rotation in the acyclic radical cation intermediate is also possible since C–C forming barriers are higher. Computations are consistent with the experimental observation that hexafluoroisopropanol (HFIP) is a better solvent than acetonitrile, in part due to its ability to stabilise the reduced form of the hypervalent iodine initiator by hydrogen bonding, but also through the stabilisation of radical cationic intermediates along the reaction coordinate.

A computational study details the mechanism, catalytic cycle and origins of stereoselectivity underlying hole-catalyzed intermolecular alkene heterodimerisation to give unsymmetrical, tetra-substituted cyclobutanes.     

Transition-metal-mediated reduction and reversible double-cyclization of cyanuric triazide to an asymmetric bitetrazolate involving cleavage of the six-membered aromatic ring

Cyanuric triazide reacts with several transition metal precursors, extruding one equivalent of N₂ and reducing the putative diazidotriazeneylnitrene species by two electrons, which rearranges to N-(1′H-[1,5′-bitetrazol]-5-yl)methanediiminate (biTzI²⁻) dianionic ligand, which ligates the metal and dimerizes, and is isolated from pyridine as [M(biTzI)]₂Py₆ (M = Mn, Fe, Zn, Cu, Ni). Reagent scope, product analysis, and quantum chemical calculations were combined to elucidate the mechanism of formation as a two-electron reduction preceding ligand rearrangement.

Cyanuric triazide reacts with transition metal precursors, extruding N₂ and reducing the ligand by two electrons, which breaks an aromatic ring and rearranges to a bitetrazolylmethanediiminate (biTzI²⁻) ligand, forming two new aromatic rings.     

Ligand-controlled and nanoconfinement-boosted luminescence employing Pt(ii) and Pd(ii) complexes: from color-tunable aggregation-enhanced dual emitters towards self-referenced oxygen reporters

In this work, we describe the synthesis, structural and photophysical characterization of four novel Pd(ii) and Pt(ii) complexes bearing tetradentate luminophoric ligands with high photoluminescence quantum yields (Φ_L) and long excited state lifetimes (τ) at room temperature, where the results were interpreted by means of DFT calculations. Incorporation of fluorine atoms into the tetradentate ligand favors aggregation and thereby, a shortened average distance between the metal centers, which provides accessibility to metal–metal-to-ligand charge-transfer (³MMLCT) excimers acting as red-shifted energy traps if compared with the monomeric entities. This supramolecular approach provides an elegant way to enable room-temperature phosphorescence from Pd(ii) complexes, which are otherwise quenched by a thermal population of dissociative states due to a lower ligand field splitting. Encapsulation of these complexes in 100 nm-sized aminated polystyrene nanoparticles enables concentration-controlled aggregation-enhanced dual emission. This phenomenon facilitates the tunability of the absorption and emission colors while providing a rigidified environment supporting an enhanced Φ_L up to about 80% and extended τ exceeding 100 μs. Additionally, these nanoarrays constitute rare examples for self-referenced oxygen reporters, since the phosphorescence of the aggregates is insensitive to external influences, whereas the monomeric species drop in luminescence lifetime and intensity with increasing triplet molecular dioxygen concentrations (diffusion-controlled quenching).

Pt(ii) and Pd(ii) complexes with unprecedented photophysical properties were developed. Encapsulation in nanoparticles boosted their performance while rendering them as self-referenced oxygen sensors.     

Pd-catalyzed cross-electrophile Coupling/C–H alkylation reaction enabled by a mediator generated via C(sp3)–H activation

Transition-metal-catalyzed cross-electrophile C(sp²)–(sp³) coupling and C–H alkylation reactions represent two efficient methods for the incorporation of an alkyl group into aromatic rings. Herein, we report a Pd-catalyzed cascade cross-electrophile coupling and C–H alkylation reaction of 2-iodo-alkoxylarenes with alkyl chlorides. Methoxy and benzyloxy groups, which are ubiquitous functional groups and common protecting groups, were utilized as crucial mediators via primary or secondary C(sp³)–H activation. The reaction provides an innovative and convenient access for the synthesis of alkylated phenol derivatives, which are widely found in bioactive compounds and organic functional materials.

A cascade Pd-catalyzed cross-electrophile coupling and C–H alkylation reaction of 2-iodo-alkoxylarenes with alkyl chlorides has been developed by using an ortho-methoxy or benzyloxy group as a mediator via C(sp³)–H activation.     

Pressure-induced phosphorescence enhancement and piezochromism of a carbazole-based cyclic trinuclear Cu(i) complex

Interest in piezochromic luminescence has increased in recent decades, even though it is mostly limited to pure organic compounds and fluorescence. In this work, a Cu₃Pz₃ (Cu3, Pz: pyrazolate) cyclic trinuclear complex (CTC) with two different crystalline polymorphs, namely 1a and 1b, was synthesized. The CTC consists of two functional moieties: carbazole (Cz) chromophore and Cu3 units. In crystals of 1a, discrete Cz–Cu3–Cu3–Cz stacking was found, showing abnormal pressure-induced phosphorescence enhancement (PIPE), which was 12 times stronger at 2.23 GPa compared to under ambient conditions. This novel observation is ascribed to cooperation between heavy-atom effects (i.e., from Cu atoms) and metal–ligand charge-transfer promotion. The infinite π–π stacking of Cz motifs was observed in 1b and it exhibited good piezochromism as the pressure increased. This work demonstrates a new concept in the design of piezochromic materials to achieve PIPE via combining organic chromophores and metal–organic phosphorescence emitters.

One molecule, two response mechanisms: a pair of newly-designed cyclic trinuclear Cu(i) complex crystalline polymorphs are engineered, which show excellent luminescent piezochromism and pressure-induced phosphorescence enhancement, respectively.     

Visible light driven generation and alkyne insertion reactions of stable bis-cyclometalated Pt(iv) hydrides

Hydride complexes resulting from the oxidative addition of C–H bonds are intermediates in hydrocarbon activation and functionalization reactions. The discovery of metal systems that enable their direct formation through photoexcitation with visible light could lead to advantageous synthetic methodologies. In this study, easily accessible dimers [Pt₂(μ-Cl)₂(C^N)₂] (C^N = cyclometalated 2-arylpyridine) are demonstrated as a very convenient source of Pt(C^N) subunits, which promote photooxidative C–H addition reactions with different 2-arylpyridines (N′^C′H) upon irradiation with blue light. The resulting [PtH(Cl)(C^N)(C′^N′)] complexes are the first isolable Pt(iv) hydrides arising from a cyclometalation reaction. A transcyclometalation process involving three photochemical steps is elucidated, which occurs when the C^N ligand is a monocyclometalated 2,6-diarylpyridine, and a detailed analysis of the photoreactivity associated with the Pt(C^N) moiety is provided. Alkyne insertions into the Pt–H bond of a photogenerated Pt(iv) hydride are also reported as a demonstration of the ability of this class of compounds to undergo subsequent organometallic reactions.

The photochemical generation of isolable bis-cyclometalated Pt(iv) hydrides via photooxidative C–H addition reactions is demonstrated from easily accessible Pt(ii) precursors using visible light.