Functionalised MnVI-nanoparticles: an advanced high-valent magnetic catalyst

We discover MnVI-nanoparticles (NPs) bearing functional groups, high oxidation state, strong electron affinity, unique redox and paramagnetic nature, which opens up a new avenue to catalysis, magnetism and material application. However, its synthesis is challenging and remains unexplored because of associated serious difficulties. A simple benign synthetic strategy is devised to fabricate the high-valent NPs using mild reducing agent bromide, which transformed MnVII to valuable MnVI-species. The EELS-imaging of individual elements, ESI-MS, XPS and other techniques established its composition as Br(Me3SiO)MnVIO2. It revealed significantly improved magnetic moment (SQUID) with isotropic hyperfine splitting of six line spectrum (EPR). The high-oxidation state and incorporated-ligands of the metals present on the active surface of the NPs led to development of a general catalytic process for oxidative heterodifunctionalisation to C-C triple bond towards formation of a new O-C/N-C/S-C and C-C coupling cum cyclisation to biologically important flavones and their aza- and marcapto-analogues, and valuable enaloxy synthons.

Results Design, synthesis and EELS study of the Mn VI -NPs. The simple Mn VII salt KMnO 4 was selected as a precursor to design the XYMn VI Z 2complex bearing -X, -Y and -Z-groups (eq. 1, Figure 1). We envisioned that the groups such as -I, -Br, -Cl, -OSiMe 3 , -OTf, -O-, -S-etc. possessing good leaving and insertion properties to material will be helpful to accommodate the organic precursors for bond activation around the high-valent metal-sites accomplishing a robust catalysis.
After several experiments we found trimethyl silyl bromide as an effective reducing agent to the precursor KMn VII O 4 towards fabrication of Mn VI -NPs in CH 2 Cl 2 containing cetyltrimethyl ammonium bromide (CTAB, 10 mol%) at ambient temperature. The NPs were collected from the surfactant-assembled nanospace after one hour of reductive fabrication of the NPs, precipitation of the nanomaterial by addition of CH 2 Cl 2 , collection through centrifuge and successive washing of the brown colour residue (panel A, Figure 1). The dynamic light scattering measurement of the dilute reaction mixture in CH 2 Cl 2 revealed maximum population of the NPs at 15.4 nm (panel A, Figure 1). However, the high resolution transmission electron microscope (HR-TEM) imaging of the nanomaterial was inconclusive to determine its morphology. It might be due to rapid damage (panel B, Figure 2) on their organic component-bearing surface by the strong electron-beam of TEM, high reactivity of the metal component of highly oxidation state and/or weak signal generation from the thin nanomaterial. Recently, scanning transmission electron microscope -Electron Energy Loss Spectroscopy (STEM-EELS) is emerging as a powerful tool for elemental mapping of nanomaterials [51][52][53][54] . Our EELS study for the Mn VI -NPs revealed presence of worm-like NPs (panel C, Mn only). The mapping of all atoms such as Mn, O, Si, C, Br and H was established by the EELS study. The composite EELS image displayed in panel D and other individual images are supplied in the supporting information. Worm like structure has also been confirmed using AFM study.
To understand the mechanism of fabrication process of the nanomaterials we analyzed a dispersed monolayer material, which was taken out from the ongoing reaction. Gratifyingly it revealed presence of small cube-like NPs along with relatively larger cube-like structure (green circles, panel E) as well as small worm-like structures (yellow circle), which was imaged on dark field (DF) scanning transmission electron microscope. Combination of four small NPs to form the actual unit cell is visible in the panel B with dark-red circle which ultimately construct the worm-like thin NPs. Interestingly the smallest one can couple among four units to form larger cubical nanomaterial which also can arrange nicely between three to four units to form worm-like NPs (,13 nm). The proposed scheme is presented in the panel F. The reaction mixtures exhibit two UV-vis   absorption peaks at 514.1 and 534.9 nm, which also support presence of Mn VI -NPs of two different size in the reaction mixture.
Elucidation of structure of the Mn VI -NPs. The orange line in the panel (i), Figure 3 corresponds to the XPS spectrum of the assynthesized Mn-NPs, which indicates presence of manganese in the 16 oxidation state 55 . The pink line in panel (ii), Figure 3 represents the XPS spectrum of the recovered manganese catalyst from the reaction mixture. The deconvolution graph (violet line) was found after fitting the data in XPS software. It showed presence of a mixture of Mn VI and Mn IV in the recovered material, which matches with the standard curve for Mn VI (orange line) and Mn IV (green line). The powder X-ray diffraction peaks (2h) of the solid Mn-NPs appeared at 28.1u, 40.2u, 49.8u, 58.1u, 66.1u and 73.1u. Electronspray ionizationmass spectrometry (ESI-MS) of the NPs is performed in CH 3 CN medium and the appearance of ESI-MS-generated peak at 254.8885 dalton established the composition Mn VI -NPs as Br(Me 3 SiO)MnO 2 . Presence of (CH 3 ) 3 SiOMn group was verified by measurement of FTIR spectroscopy of the nanomaterial, which revealed appearance of FTIR stretching vibration for C-H at 2922 cm 21 , Si-O at 1393 cm 21 and Mn VI -O broad peaks around 511 cm 21 . The peak at d 1.46 in the solid state 1 H-NMR confirmed the presence of methyl group of -OSi(CH 3 ) 3 in the functionalized NPs. All other spectra are available in the supporting information.
Unusual nanoscale magnetism of the high-valen Mn VI -NPs. Interestingly, spin only magnetic moment of Mn VI -complex in nano-state is found to be 2.2 BM at room temperature, which is unusually high relative to the expected value (,1.73 BM) of bulk-Mn VI compound bearing 3d 1 electron. The X-band EPR spectrum (panel G, Figure 4) of the powdered nanomaterial at 278uC (liquid N 2 ) showed a significantly improved isotropic hyperfine splitting 55 31 -complex 56 . The higher value of magnetic moment of the small nanomaterial and hyperfine splitting in EPR spectrum may be attributed due to their exceptionally high oxidation state and existence of magnetic vector in an unidirectional 56 fashion. It led us to execute the temperaturedependent SQUID measurement 57 of the nanomaterial, which also revealed (panel H) higher magnetic moment (2.2 BM). It clearly indicates the special arrangement (F, Figure 1) of the tiny high-valent magnetic NPs (vector) which eventually added the vector towards significant enhancement of the magnetic moment.
Discovery of C-X/C-C coupled annulation catalysis. Design, synthesis and development of new catalytic activity of a material are of intense interest to the chemical science community because the catalyst offers novel reactivity and selectivity towards synthesis of valuable compounds. An annulation reaction that can selectively execute O-C/C-C coupling through grafting of C-C triple bond is a very promising strategy towards direct construction of functionalised analogues of natural product flavones (6, eq. 2, Figure 5). Herein, we for the first time synthesize Mn VI -NPs, developed outstanding catalytic activity for O-C/N-C/S-C 20,25 and C-C coupled annulation to flavone skeletons (6-8) and enaloxy synthons (9), easy recovery of the magnetic catalyst from the post reaction mixture by using external magnet and successfully recycled, and several facets of catalysis for C-C triple bond functionalisation reactions. We first observed the oxidative coupling between functionalized salicylaldehyde derivative (1a, entry 1) and a deactivated alkyne (2a) to undergo annulation reaction at ambient temperature in THF towards direct construction of valuable flavones (6a, 20% yield) in presence of catalytic amount (10 mol%) of the Mn VI -NPs, NaIO 4 (1.1 mmol) and triethylamine. Gratifyingly the reaction was complete in 4 h and yield (80%) as well as catalyst loading (10 mol%) were improved by rising the reaction temperature to 70uC. NaIO 4 was needed as a stoichiometric oxidant for the O-C and C-C coupled annulation process because the yield  was drastically reduced (7%) in its absence under the optimized conditions. On carrying out the reaction using bulk-Mn VI compound as a catalyst conversion of the starting material was very poor (,40% conversion) even after prolong heating (,24 h). Similarly, the product 6a was not found in absence of the catalyst. It indicates that surface of the functionalized Mn VI -NPs is highly active towards binding the precursors (1a and 4a) which led to grafting of the triple bond with rapid annulation. This catalytic strategy was helpful for synthesis of a large number of flavones (6a-k, entries 1-11) within 3-4 h by varying the starting ingredients. Methyl, halogen, methoxy etc. substituted aromatic rings, heterocycles, carbonyl, ester functionalities were tolerated under the above optimized reaction conditions. The feasibility of the reaction was also checked with highly deactivated alkyne such as diethyl acetylene dicarboxylate, which produced the desired flavones (6a, 6i and 6j). Interestingly, the functionalized surfaces of high-valent-NPs are very much site-selective for binding the precursors which led to complete regioselective annulation to compound 6. The other possible regioisomer 10 (eq. 2) was not found using unsymmetrical alkynes (entries 2-8). The nitrogen analogues of flavones i.e. 4-quinolinones (7a-c, entries 12-14) and marcaptoflavones (8a,b, entries [15][16] were also been synthesized using 2aminobenzaldehyde and 2-marcaptobenzaldehyde respectively under the similar reaction conditions. Thus, the newly synthesized highvalent Mn VI -NPs were found as robust catalyst for developing a rapid and general strategy to bioactive flavone analogues with outstanding regioselectivity and high yield. Surprisingly on replacement of carbonyl group by alcoholic -OH in the triple bond the C-C coupled annulation was completely unsuccessful to afford corresponding flavone (6, entry 17). In turn, it underwent C-C coupling with another aldehyde functionality to afford highly functionalised valuable enaloxy synthons (9a-c, entries [17][18][19] in 4 h with 65-76% yield. The possible role of the high-valent Mn VI -NPs in the robust catalysis. Exact mechanism of the catalytic process is unknown to us. However, high oxidation state of the Mn VI -NPs, catalytic site-preference, metalbearing good leaving groups, and highly active nanoscale-surface with strong electro affinity of the NPs lead to activation of the precursor aldehyde (1-3) and alkyne (4) through formation of an assembly (I, eq. 3, Figure 6) involving C-C triple bond, carbonyl oxygen and -XH. In this step bromide was lost from the NPs and Mn-X bond was formed. The reactive intermediated II is expected to form by deprotonation of aldehyde through -CO-H activation and regioselective nucleophilic addition of -X from C 3 of the alkyne (4) to generate O-C/N-C/S-C bond. During optimization of the reaction we observed that presence of base NEt 3 was essential in the catalysis process, which might be needed to abstract aldehyde-sp 2 C-H for transforming I to II. The desired product 6, 7 or 8 was produced via oxidative C-C coupling of the allene-like intermediate(II) with insertion of bromide and release of reduced Mn IV -modified NPs. Trace amount of Mn IV along with Mn VI was detected via XPS analysis of the recovered catalyst from the ongoing reaction mixture. (SI) Catalytic cycle is maintained through regeneration of the Mn VI -NPs at the surface by the stoichiometric oxidant sodium metaperiodate (NaIO 4 ) under the reaction conditions. To understand whether the involvement of carbonyl oxygen of the alkyne with the high-valent Mn VI -NPs is essential for the oxidative C-C coupled annulation process we used its reduced form i.e. propargyl alcohol (5) under the similar reaction conditions. However, corresponding oxidative C-C coupled annula- tion product (6, Figure 5) involving aldehyde group of salicylaldehyde (1) was not found from the post reaction mixture. It supports our proposed reaction pathway, which passes through initial coordination of the carbonyl oxygen of 4 (I) with Mn VI -NPs. Interestingly the highvalent-NPs completely changed the O-C/C-C coupling reaction path and it was joined to another molecule of salicylaldehyde with simultaneous oxidation of -CH 2 OH of 5 to aldehyde affording highly functionalized synthon 9a (entry 17, Figure 5). The catalytic three component coupling process was also successfully carried out in presence of other aldehydes (9b,c, entries 18,19). It indicates that oxidation took place after the Mn VI -NPs catalyzed cascade type of O-C and C-C coupling, which is expected to proceed through formation of two successive six member transition states III and IV (eq. 4, Figure 6). XPS studies (Figure 3) showed that recovered catalyst was the mixture of Mn IV and Mn VI , which were very difficult to separate for characterization. It supports our proposed reaction pathway, which passes through transformation of intermediate II to desired product (6)(7)(8) with generation of Mn IV -species ( Figure 6). Interestingly we observed in our experiments using the recovered catalyst that it was equally efficient to as-fabricated Mn-NPs in presence of NaIO 4 due to transformation of Mn IV to Mn VI under the reaction conditions.

Discussion
In this article, we have demonstrated an innovative design and fabrication of a functionalised high-valent nanomaterial through formation of a new Mn VI -compound under benign reaction conditions. Herein, we report an unprecedented reductive transformation of readily available Mn VII -salt KMnO 4 to valuable Mn VI -species using Me 3 SiBr as a mild reducing agent. The Mn VI -NPs bearing uncommon six oxidation state, exchangeable ligands, catalytic-site preference possibility, strong electron affinity, unique redox and magnetic property is the potential candidate for unique magnetism, material and catalysis. However, fabrication of well defined high-valent metal-NPs is a difficult job because of its higher oxidation state, reactivity and less stability under the heating conditions which is usually required during synthesis of a nanomaterial. Herein, a benign strategy is devised for fabrication of the high-valent metal-NPs of uniform size and shape through in situ generation of the ingredient and creation of nanospace utilizing inexpensive KMnO 4 , Me 3 SiBr and CTAB (Figure 7). The modern EELS imaging technique is used for mapping of individual elements present in the nanomaterial and it revealed formation of worm-like structure. The possible mechanism of unidirectional packing of the nanomaterial is also predicted (panel F, Figure 2) with the experimental evidence. The primary formula of the NPs was established as Br(Me 3 SiO)Mn VI O 2 . A significantly improved magnetic property was observed in the X-band ESR spectroscopy of the NPs with isotropic hyperfine splitting of six line spectrum (panel G, Figure 7). It also showed higher magnetic moment with respect to common Mn VI -compounds (d 1 ), which is comparable to the temperature dependant SQUID data (panel H). As expected the high-oxidation state and incorporated-ligands of the metals present on the active surface of the NPs was crucial to develop a robust catalytic process for oxidative heterodifunctionalisation of C-C triple bond towards formation of a new O-C/C-C coupling cum cyclisation to afford a wide range of biologically important flavone (6a-k, eq. 5, Figure 7) compounds. Herein, we have introduced a general strategy for direct construction of the bioactive flavone with outstanding regioselectivity and its analogues such as azaflavones (7a-c, eq. 6) and marcaptoflavones (8a,b, eq. 7), and a valuable 3-oxyenal synthon (9a-c, eq. 8) involving and N-C/S-C/O-C and C-C coupling, which is quite important to synthetic and medicinal chemistry -the most active area of contemporary research. We believe that the intriguing and inspiring strategy for fabrication of the functionalized high-valent metal-NPs, its unique magnetic property and diverse catalytic activity will open up a new avenue in science and technology.

Methods
Synthesis of Mn VI -NPs. In a 100 mL round bottomed flask, CTAB (364 mg, 1 mmol) and CH 2 Cl 2 (36.4 mL) were taken together and stirred magnetically for 5 min. KMnO 4 (158 mg, 1 mmol) was added into the solution and stirring was continued. Me 3 SiBr (306 mg, 2 mmol) was added drop wise at 0uC and content of the reaction mixture was stirred for 45 min. Finally the reaction mixture was poured into 200 mL of CH 2 Cl 2 and centrifuged, washed with CH 2 Cl 2 (5 3 20 mL) and dried under reduced pressure at ambient temperature to afford Mn VI -NPs as a brown solid material (yield: 52%; 138 mg, 0.52 mmol). The characterization data of the new nanomaterial such as FTIR, NMR, ESI-MS, powder XRD, UV-vis, AFM, FESEM-EDS for elements, EELS elemental mapping and the important spectra are incorporated in the supporting information.