August 8, 2021 - Free Activators

You need a free license key for Office 2019, Professional, Look under the product information title and find the activation status of the office. PNAS | Published online August 24, 2015 | E4975–E4984. BIO. CHEMISTRY. PNAS. PLUS. Downloaded at Google Indexer on August 8, 2021. This fun, annual, free event is sponsored by Alaska Airlinesand the Atwood Foundation The 2021 season runs from June 17th to August 5th.

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How to Activate Windows 10 for Free in 2021 - Direct \u0026 CMD Method

Depending on how you look at them, new moons — which are all about new beginnings and starting fresh — can either be wonderfully refreshing or kind of daunting. And however you think of them, this week's astrological event may be a bit more chaotic than we're expecting. On August 8, there will be a new moon in fiery Leo, and astrologers are already saying it will be "super intense." Are you ready for the ride?

One way to think of new moons is as a double dose of astrological energy, because during them, the moon and the sun are always in the same zodiac sign, explains Narayana Montúfar, senior astrologer for and author of Moon Signs: Unlock Your Inner Luminary Power. "In this case, the new moon is a double dose of the lion's fire and can-do energy," she says. If you've been feeling like the main character during the spotlight-craving Leo season, prepare for things to get even spicier as the moon enters into the fire sign too.

Leo has many wonderful traits, including generosity and compassion. Now is a good time to turn those characteristics inward and focus on your own desires and needs. "This new moon wants you to dive deeper into what your heart needs from you right now," says Madi Murphy, co-founder of The Cosmic RX and The Cosmic Revolution. "Think: tapping into your inner child’s joy, having more self-compassion, living with more presence, feeling more open to life, or finding what lights your soul up."

The date of this new moon, 8/8, is especially auspicious due to something known as the lion's gate portal that happens every year on August 8. "For thousands of years, this has been observed and honoured as a time of a great energetic influx and activation," Murphy says. "This gateway is marked by an alignment between the Earth and the star Sirius (the brightest star we can see). As Sirius rises in the sky, Orion's Belt directly aligns with the Pyramid of Giza, and from our perspective on Earth, it appears that Sirius comes closer to the Earth." Murphy says this is a time of "increased cosmic energy flowing between the physical and spiritual realms," and that it's a good time to manifest, set intentions, and connect with your Higher Self.

This new moon has a serious side, though. It will set off a Saturn and Uranus square, a tense pairing can has a way of instigating major changes, says Lisa Stardust, the author of Saturn Return Survival Guide and The Astrology Deck. Because of this, now is the time to make a big shift in our lives, even if we don't necessarily feel super-ready for them. It may sound a bit scary, but Stardust has a point. "In true cosmic form, if we don’t make growth, the universe will do it for us," she says. "Therefore, it’s best to get a handle and take control as to how we can evolve our lives on our terms."

You may be better off focusing on creating necessary endings than new beginnings. Montúfar says that the T-square forming between the moon and these two planets is bringing an unpredictable energy. "This new moon is highlighting all the change we are going through this year, and its influence might be better for breaking old microsoft office 365 product key hack - Activators Patch and habits than for planting seeds of intention," she says. "T-squares are moments of crisis and wake-up calls, and this new moon is surely going to deliver an important message." Now is the time to let go of what isn't serving you, whether it's bad habits, bad friends, or even bad jobs. While there's no need to search for answers just yet, acknowledging what must be done to create meaningful change is a good first step.

Murphy says that this transit — especially with Uranus being activated — can make us feel scattered, anxious, or uncertain about things that we were once very certain about. But being uncertain isn't necessarily a nail in our collective 2021 - Free Activators. "This shaking of our reality can help us see things in a new light, understand new perspectives in life, and evolve," Murphy says. "Uncertainty can open us up to our full potential, but the key is to stay present and learn how to release our attachment to control."

The vibes of this new moon are intense — we warned you! — but as long as you focus your energy on embracing the strong Leo energy, you'll be able to make it out on the other side.


U.S. Bank Visa

How to Activate Debit or Credit Card

Online banking steps:

To get started, log into online banking and follow these steps:

  1. Select Customer Service from the top menu bar and then select Self Service.
    • For debit cards: Select Activate Debit/ATM Card under the Debit Card & ATM Card section.
    • For credit cards: Activate a Card under the Credit/Charge Account section.
  2. Input the card information and follow the prompts to complete the activation.

U.S. Bank Mobile App steps:

For the best mobile banking experience, we recommend logging in or downloading the U.S. Bank Mobile App.

  1. From the main menu select Manage cards.
  2. Select the card requiring activation.
  3. Select Activate Card. If you have multiple cards awaiting activation, choose the one you’d like to activate and select Continue.
  4. Provide your card information and last four digits of your SSN, then select Activate.

Additional information:

Debit cards: Your Personal Identification Number for your debit card (PIN) arrives separately for your security. It can also be activated by making a deposit or withdrawal at any U.S. Bank ATM. If you’d like to call to activate your card. contact us at 800-236-3838.


Important: Windows 7 and Windows Server 2008 R2 have reached the end of mainstream support and are now in extended support. Starting in July 2020, there will no longer be optional, non-security releases (known as "C" releases) for this operating system. Operating systems in extended support have only cumulative monthly security updates (known as the "B" or Update Tuesday release).

Verify thatyou have installed the required updates listed in the How to get this update section before installing this update. 

For information about the various types of Windows updates, such as critical, security, driver, service packs, and so on, please see the following article. To view other notes and messages, see the Windows 7 and Windows Server 2008 R2 update history home page.

Improvements and fixes

This security update includes improvements and fixes that were a part of update KB5004289 (released July 13, 2021) and addresses the following issues:

  • Changes the default privilege requirement for installing drivers when using Point and Print. After installing this update, you must have administrative privileges to install drivers. If you use Point and Print, see KB5005652, Point and Print Default Behavior Change, and CVE-2021-34481 for more information.

  • Addresses an issue in which Smart Card Authentication (PIV) fails on non-RFC compliant printers and scanners requiring smartcard authentication. For more information, see KB5005392.

  • This update also contains miscellaneous security improvements to internal OS functionality.

For more information about the resolved security vulnerabilities, please refer to the new Security Update Guide website.

Known issues in this update

How to get this update



After installing this update, the Encrypted File System (EFS) API OpenEncryptedFileRaw(A/W), often used in backup software, will not work when you back up to or from a Windows Server 2008 SP2 device. OpenEncryptedFileRaw will continue to work on all other versions of Windows (local and remote).

This behavior is expected because we addressed the issue in CVE-2021-36942.

Note If you cannot use backup software on Windows 7 SP1 and Server 2008 2021 - Free Activators SP1 or later after installing this update, contact the manufacturer of your backup software for updates and support.

After installing this update and restarting your device, you might receive the error, "Failure to configure Windows updates. Reverting Changes. Do not turn off your computer", and the update might show as Failed in Update History.

This is expected in the following circumstances:

  • If you are installing this update on a device that is running an edition that is not supported for ESU. For a complete list of which editions are supported, see KB4497181.

  • If you do not have an ESU MAK add-on key installed and activated.

If you have purchased an ESU key and have encountered this issue, please verify you have applied all prerequisites and that your key is activated. For information on activation, please see this blog post. For information on the prerequisites, see 2021 - Free Activators How to get this update section of this article.

Certain operations, such as rename, that you perform on files or folders that are on a Cluster Shared Volume (CSV) may fail with the error, "STATUS_BAD_IMPERSONATION_LEVEL (0xC00000A5)". This occurs when you perform the operation on a CSV owner node from a process that doesn’t have administrator privilege.

Do one of the following: 

  • Perform the operation from a process 2021 - Free Activators has administrator privilege.

  • Perform the operation from a node that doesn’t have CSV ownership.

Microsoft is working on a resolution and will provide an update in an upcoming release. 

Before installing this update

IMPORTANT Customers who have purchased the Extended Security Update (ESU) for on-premises versions of these operating systems must follow the procedures in KB4522133 to continue receiving security updates after extended support ends. Extended support ends as follows:

  • For Windows 7 Service Pack 1 and Windows Server 2008 R2 Service Pack 1, extended support ends on January 14, 2020.

  • For Windows Embedded Standard 7, extended support ends on October 13, 2020.

For more information about ESU and which editions are supported, see KB4497181.

Note For Windows Embedded Standard 7, Windows Management Instrumentation (WMI) must be enabled to get updates from Windows Update or Windows Server Update Services.


You must install the updates listed below and restart your device before installing the latest Rollup. Installing these updates improves the reliability of the update process and mitigates potential issues while installing the Rollup and applying Microsoft security fixes.

  1. The March 12, 2019 servicing stack update (SSU) (KB4490628). To get the standalone package for this SSU, search for it in the Microsoft Update Catalog. This update is required to install updates that are only SHA-2 signed.

  2. The latest SHA-2 update (KB4474419) released September 10, 2019. If you are using Windows Update, the latest SHA-2 update will be offered to you automatically. This update is required to install updates that are only SHA-2 signed. For more information on SHA-2 updates, see 2019 SHA-2 Code Signing Support requirement for Windows and WSUS.

  3. For Windows Thin PC, you must have the August 11, 2020 SSU (KB4570673) or a later ExpanDrive 7.6.4 Crack License key Free (Win+Mac) installed to make sure you continue to get the extended security updates starting with the October 13, 2020 updates.

  4. To get this security update, you must reinstall the "Extended Security Updates (ESU) Licensing Preparation Package" (KB4538483) or the "Update for the Extended Security Updates (ESU) Licensing Preparation Package" (KB4575903) even if you previously installed the ESU key. The ESU licensing preparation package will be offered to you from Glary utilities pro key crack - Crack Key For U get the standalone package for ESU licensing preparation package, search for it in the Microsoft Update Catalog.

After you install the items above, we strongly recommend that you install the latest SSU (KB5004378). If you are using Windows Update, the latest SSU will be offered to you automatically if you are an ESU customer. To get the standalone package for the latest SSU, search for it in the Microsoft Update Catalog. For general information about SSUs, see Servicing stack updates and Servicing Stack Updates (SSU): Frequently Asked Questions.

Install this update

Release Channel


Next Step

Windows Update and Microsoft Update


None. This update will be downloaded and installed automatically from Windows Update if you are an ESU customer.

Microsoft Update Catalog


To get the standalone package for this update, go to the Microsoft Update Catalog website.

Windows Server Update Services (WSUS)


This update will automatically sync with WSUS if you configure Products and Classifications as follows:

Product:  Windows 7 Service Pack 1, Windows Server 2008 R2 Service Pack 1, Windows Embedded Standard 7 Service Pack 1, Windows Embedded POSReady 7, Windows Thin PC

Classification: Security Updates

File information

For a list of the files that are provided in this update, download the file information for update 5005088.

PCs Microsoft

KMSPico is the activator that is used to activate Microsoft Products, such as Windows and Office. It is a total virus and malware-free tool and trusted by many people.

I personally use it for Windows activation. This amazing activator works without the internet, and it’s very easy to use.

If you are not getting the premium feature of windows in free, then KMSpicois a handy tool for activating windows and enjoy these features for free with the help of this tool

This Software developed by respected TeamDaz and also known as Windows 10 activator, they have also made other KMS tools like KMSAuto,Windows August 29, 2021 - Free Activators loaderwhich work automatically they are going well for us

So if anyone has a problem activating windows just follow this simple guide to learn how you can do it easily, also you will find the download link.

What is KMSPico?

KMSPico is used to validate the pirated version of Microsoft Windows and MS Offices. However, this KMS technology is introduced by Microsoft for mutual gain, without getting exposed by Microsoft.


KMSPico is also the software of those technologies which doesn’t violate the rules of Microsoft. It’s just like a local server that lets every machine use KMS Technology.!

It doesn’t only helps you in activating Windows OS it also helps you to activate the MS Office which is also a Microsoft product.

You know that the new versions of MS office are required to be activated to use their full features. It comes with some days of trial. When the trial ends you need to activate it to use it again. That’s why this activator is also helpful for activating it.

How KMSPico Works

To understand the concept of KMSPico you first need to understand how KMS works. We are taking an example of Microsoft so that you can learn properly.

As you know that Microsoft works with many small and big companies. So the people of those companies have the problem of verifying the windows or other products they are using.

To solve this problem Microsoft assigns the Key Management Server (KMS). This way they don’t need to enter the Windows product key to activate their Windows. Instead, they go through the KMS server and this server activates their Microsoft products.

This way Microsoft achieved an activation of the volume licensed products. So, now every company uses the KMS server instead of buying a separate copy of windows for every system.

It also works on the same principle. It connects you to the KMS server and shows 2021 - Free Activators windows that it is a part of the KMS server.

Download KMSpico

What KMS Pico Does


When you buy a copy of a Windows or Microsoft products you will get the trial version of that product. Some of them consist of keys otherwise they came in the trial versions.

Trial versions are limited to almost 30 days. When the trial expires you will have to activate the product to use it more.

When the trial expires you can’t use some features of Windows or MS Office. In this case, you need to have an activator so that you can use that product for a lifetime.

KMS Pico is an example of such software that helps you to activate Microsoft products so that you can use it for the rest of your life for free.

There are many other tools that are available on the August 8 which gives their users a guarantee that they will activate it. But most of those activators have trojans and malware that damage your machine.


This is the best activator because it not only activates Windows but also activates Office as well. Here is the list of all the products which Activator Supports:

  • Windows 10
  • Windows 8.1
  • Windows 8
  • Windows
  • Windows Vista
  • MS Office 2016
  • Office 365
  • Office 2013
  • Office 2010
  • Office 2007

We will keep updating it if we found another supported product or found any new information about the activator.

Download KMSpico

Downloading KMSPico is not a big deal. I am providing you with a direct link from where you can download easily without facing any issue.

Download KMSpico

Let’s now look at the steps of how to download.

  • First of all click on the download button Above.
  • Then you will be redirected to our download page.
  • There you can see a download button available.
  • Click on that download button and wait for a few seconds.
  • Now it will ask you where you want to save it. Choose your desired location and click on download now.
  •  It will take a few minutes to download. (Depends on your internet speed).
  • You will get a zip file, extract that file and it will ask you for a password.
  • You can find the password on the download page

That’s all now you have successfully downloaded it on your computer. Now if you don’t know how to install and activate your windows you can follow my Installation guide.


As you read all the above information about the tool driver booster 6.4 license key - Activators Patch here is a full guide on How you can download and install the windows activator.

Follow these steps so that you can also enjoy the fully activated windows and ms office for a lifetime. This is very easy to install and use an activator.

First of all, you need to turn off the firewall and Antivirus (Don’t worry it’s not a trojan or any virus. Antivirus blocks it because they know this will activate the windows


If you are using windows 10 then follow these steps to pause the Virus Protection.

Search for the Protection and open Virus & Threat Protection


Now click on Virus & Threat Protection Settings.


And then turn off Real-Time Protection.


After the above steps now Download KMSPico From our website.

  • If you find any link is broken or unavailable Inform us so that we can update it as soon as possible. Also, you just go for another link.
  • Once your download is completed just install it like other software.
  • When your installation is completed just go to the installation directory. (You will find the directory in C/ProgramFiles/KMSPico (x84 or x32) C/ProgramFiles(x84)/KMSPico (x64).
  • Now look for the KMSeldi.exe and double click on it to open.
  • Run it anyway if it asks for the administration privilege.! (See the screenshot).


Now a newwindow will pop up and you will see a red button.


Just click on that redbutton and it will take only a few seconds to complete activation. When it completes you will hear a voice saying ProgramComplete!


That’s it, now you have activated the windows Successfully.

To activate the MS Office you first need to open any of their programs just like Microsoft Excel or Word. Then just follow those above steps to activate it. When it’s completed just restart your machine and check out if your windows are activated or not.

To Check your activation just simply right-click on My Computer and then go to Properties.


Now you will use all the features of Microsoft Windows and Microsoft Office lifetime.

How to Activate Windows 10

Key Characteristic

It helps you in activating the windows as well as office products. With the help of this tool, enfocus pitstop pro 2020 v20 0.1122552 multilingual can enjoy the activated Microsoft products for the rest of your life without purchasing it.

Also, it automatically activates the windows when you update it. You don’t need to follow again those steps for that.

This tool is a free lifetime. You can use it to use all the paid features of ms office and windows totally free. This is a lifetime free solution for Windows and Office.

The developer of KMSPico develops it in such a way that it will never be caught with any antivirus or any other thing. You can use it on many machines as you want.

This tool creates a new server on your machine so that it can activate the windows and office products according to that server.

This tool not only supports the 32 bit or 64 bit. But this works on both x32 and x62 as well.

You don’t need any type of training or huge knowledge of programs to run this tool. This is a simple and easy to use tool. It just requires a few steps to activate windows.

This is a free tool and it will remain free for a lifetime. You can use this tool anytime and anywhere without paying it.

This Activator is best to Activate Windows 10 Free Without paying anyone to get keys.


This tool has many features it is very easy to use. It has a good user-friendly UI, anyone can understand it within a few seconds.

It saves your money and time, with the help of this you can activate Microsoft Office and Microsoft windows freely without paying money.

Read the list below to learn more about these features:

  • This tool helps you to activate the different versions of Microsoft Office (from 2010 to 2016 also 365). Either is the x84 bit or x64 bit. This tool automatically detects the version of a product.
  • It is totally free and also it is a virus and malware-protected tool.
  • You don’t need to have an internet connection to use this activator. It is a fully standalone (Offline) tool.
  • This tool provides you with real and genuine activation. You don’t need to worry about being caught
  • It also supports multiples languages.
  • It requires to have.Net Framework 4.0 or above version to work it properly.

Pros and Cons

There are many benefits that KMSPico provides you from other activators. Here are some key points about this tool you can compare it with other activators if you want.

  1. It occupies less space in your PC. KMSPico occupies only 5MB on your computer.
  2. It accesses the public system
  3. It is a virus and malware-free tool.
  4. It is safe and easy to use. This tool doesn’t collect your personal data.
  5. This supports multiple languages. It is good for others who are not English speakers.
  6. It is a free tool that can be used for a lifetime. It won’t cost you even a penny.

When it comes to the Cons of this tool, We can’t find anything about this. Because it is a free and malware-free tool. What else we need?

How To Remove KMS Pico From Computer

This is a simple guide that also helps you to uninstall it from your computer.

Just follow these steps to learn how it works.

  1. Uninstall it using the “Add/Remove Program”.
  2. Deleting the KMSPico from the Google Chrome and Firefox
  3. By Removing Registry files permanently.

Here is a detailed guide about Uninstall KMSPico Completely Read it carefully so that you avoid making mistakes. if you don’t understand any step just contact us by filling the contact us form. We will help you in uninstalling it.

Frequently Asked Questions (FAQs)

As we all know that it is a type of illegal tool because piracy of any software is illegal. That’s why many people ask questions before they try to install it.

Here are some frequently asked questions which everyone wants to know. Just read this FAQ and if you have 2021 - Free Activators other just ask it in the comments or by contacting us.

We will also add it here if we find it useful for others. 🙂

Which is the official website of KMSpico?

There are several websites available that provide KMSPico to the visitors but none of them is official. However, there is only one official kmspico website is where you get 100% virus-free tools for Windows & Office.

Is KMS Activator Safe?

Yes, KMSPico is 100% safe and secure to use, although many other websites are out there that provide it as well. But the problem is none of them is legit which means you may download a virus or trojan instead Adobe Photoshop Crack With Torrent Full Version 2021 the real KMSPico tool.

Can I Delete KMSpico After Activation?

Yes, KMSPico can be deleted after the installation as it is only used to install the KMS server on your computer. Once the server is set up you can then remove it and your activation will still remain, and it automatically generates a new license in 180 days.

It shows Windows is activated but I still see that watermark saying “Your Windows is not Genuine”?

In case you follow all the steps to activate Microsoft Windows using KMSPico but still, you see Windows is not Genuine then simply restart your computer. After restart follows all the steps again and then once all steps complete restart your machine again and Voila the message disappears.

Is it permanent or my windows will automatically deactivate after some time?

KMSPico uses the Key Management Technology in which your computer requires you to get a new license every 180 days. So, once you activate your product use this tool you won’t need to follow all the steps again just make sure to connect to the internet at least once in 180 days to get a new license.

Do I need an Internet connection to Run it?

Yes, an internet connection is required in the case to install a KMS server on your computer. This works offline too but the problem is your license will be expired within months. To make it permanent just make sure to connect with the internet and then activate any product using KMSPico.


As you read everything about the This KMSpico Activator, it features its installation program, activating windows and office, and many other things.

But if you still have some questions please feel free to ask. You can ask us by filling the Contact Us form or through an email. even in the comments. We will reply to you as soon as we can.

If you like my work then share it with your friends as well. Also, add this website to your bookmark tab to reach us fast and stay updated. We keep posting the newer version if we found any.

This is everything about the KMSPico Windows 10 and MS Office Activator. If you have any further questions just contact us or comment below.


Rhodaelectro-catalyzed access to chromones via formyl C–H activation towards peptide electro-labeling


Chromones represent a privileged scaffold in medicinal chemistry and are an omnipresent structural motif in natural products. Chemically encoded non-natural peptidomimetics feature improved stability towards enzymatic degradation, cell permeability and binding affinity, translating into a considerable impact on pharmaceutical industry. Herein, a strategy for the sustainable assembly of chromones via electro-formyl C–H activation is presented. The rational design of the rhodaelectro-catalysis is guided by detailed mechanistic insights and provides versatile access to tyrosine-based fluorogenic peptidomimetics.


C–H activation has surfaced as a transformative strategy for molecular synthesis, with remarkable applications to materials science and late-stage diversification1,2,3,4,5,6. Metal-catalyzed hydroacylations have attracted major attention due to their high atom-economy, providing efficient access to substituted ketones7,8. In this context, functionalizations of hydroxy-benzaldehydes have proven to be a particularly enabling approach for the assembly of oxygen-containing heterocycles9,10,11, such as β-hydroxyketones, aurones, coumarines, and chromones12,13,14,15,16. Despite of major advances, this approach was largely limited by the need for stoichiometric amounts of chemical oxidants, compromising the inherent sustainable nature of the formyl C–H activation strategy. In recent years, a renaissance of organic electrosynthesis17,18,19,20,21,22,23 has provided a major impetus for efficient C–H activations24,25,26. Thereby, stoichiometric amounts of, often toxic, metal-containing oxidants can be avoided. Yet, while major advances in electro-organic synthesis have been noted27,28,29, challenging electro-functionalizations of oxidation-sensitive aldehydes continue to be scarce. Thus, the lability of aldehydes towards decarbonylation, overoxidation, and nucleophilic attack renders an electrochemical approach by anodic electro-oxidation particularly difficult7,8. The chromone scaffold is among others present in the commercialized drugs flavoxate and nedocromil30,31 as well as in bioactive natural products of relevance to acute myeloid leukemia32 and antiviral activity against SARS-associated corona viruses (Fig. 1a)33,34.

a Chromones as a privileged motive in pharmaceutical and bioactive compounds. b Strategy to access chromones via rhodaelectro catalysis and its use for electro-peptide labeling. c Synthesis of rhodium complex Rh-I and investigations of its redox properties by cyclic voltammetry in CH2Cl2 with nBu4NPF6 (0.2 M). d Reaction development, 0.25–0.50 mmol scale, 4.0–8.0 mL solvent, isolated yields. aWith nBu4NPF6 (0.1 M) for 4 h. Cp* pentamethylcyclopentadienyl, NaOPiv sodium pivalate, Fc ferrocene, GF graphite felt electrode, CCE constant current electrolysis, CPE constant potential electrolysis, tAmylOH 2-methyl-2-butanol.

Full size image

In this work, we present an electro-formyl C–H activation via rhodaelectro catalysis for the assembly of substituted chromones to provide sustainable access to amino acid chromone hybrids and to label peptides35,36 through metallaelectro catalysis.

Results and discussion

To put our hypothesis into practice, we designed intermediates that feature lower oxidation potentials than the sensitive aldehyde substrates themselves (Fig. 1b). To this end, a stoichiometric transformation of hydroxybenzaldehyde 1, alkyne 2 and [Cp*RhCl2]2 in the presence of base delivered rhodium(I) complex Rh-I (Fig. 1c), which was unambiguously characterized by X-ray diffraction analysis. With the proposed key intermediates in hand, we probed their redox properties towards an oxidation manifold under electrocatalytic conditions. Studies by cyclic voltammetry revealed that the complex Rh-I underwent irreversible oxidation to Rh(III) at Ep = –0.11 V vs. Fc0/+ and therefore exhibited a considerably lower oxidation potential than benzaldehyde 1 (Ep = 1.68 V vs. Fc0/+). With respect to an oxidatively induced reductive elimination from a rhodium(III/IV)-species37,38, calculations by means of DFT at the PW6B95-D3(BJ)/def2-QZVP+SMD(acetonitrile)//PBE0-D3(BJ)/def2-SVP level of theory at 298.15 K revealed an oxidation winx dvd ripper platinum blu-ray of E1/2 = 0.48 V vs. Fc0/+ of the corresponding seven-membered rhoda(III)-cycle, which is in proximity to the experimentally determined, oxidation potentials of related species at Ep/2 = 0.68 V vs. Fc0/+37,38. Further computational studies of the electro-formyl C–H activation were supportive of a kinetically, favorable oxidatively induced reductive elimination (Supplementary Fig. 21).

The isolation and electroanalytical characterization of the key intermediate set the stage for studies on the electrocatalysis, initially with a constant potential of 1.0 V vs. Fc0/+, employing [Cp*RhCl2]2 as the catalyst and NaOPiv as the base to ensure an oxidatively induced reductive elimination. Hence, the desired chromone was obtained in 57% yield (Fig. 1d, entry 2), which is in line with our initial hypothesis for the rhodaelectro-catalyzed formyl activation. Further optimization demonstrated that the reaction furnished chromone 5 likewise under user-friendly galvanostatic conditions, with tAmOH/water (3:1) as the reaction medium avoiding additional electrolytes (Fig. 1d, entry 1). Control experiments revealed the crucial role of the rhodium precatalyst (entry 3). Importantly, the reaction was also viable with commercial equipment (Fig. 1d, entry 6). To test the role of electricity in the rhodaelectro-catalyzed formyl C–H activation, we performed an in-operando monitoring of the catalysis at different currents by in situ 1H-NMR spectroscopy (Fig. 2a).

a Influence of the applied current on the reaction rate. b Competition experiment. c KIE studies.

Full size image

Indeed, the reaction rates are strongly dependent on the applied currents, indicating a turnover limiting electron transfer being operative. Additionally, an on/off experiment was conducted, clearly reflecting the key role of electricity for efficient catalyst turnover. To probe the catalysts mode of action, an intermolecular competition experiment between differently substituted salicylic aldehydes 6/7, revealed an inherent higher reactivity of the electron-rich substrate (Fig. 2b), being suggestive of a base-assisted internal electrophilic substitution-type (BIES) manifold39. A minor kinetic isotope effect was observed, again being in line with a rate limiting reoxidation (Fig. 2c).

To benchmark the presented electro-catalyzed formyl C–H activation, we compared its performance with challenging substrates 10, such as electron-deficient diphenylacetylenes and alkynes with aliphatic substituents. Thus, the efficacy towards the formation of products 1215 was found to be uniquely effective under the electrocatalytic conditions, as compared to Cu(OAc)2 as the oxidant, highlighting the superior performance of the rhodaelectro catalysis (Fig. 3a). Additionally, the scalability of the rhodaelectro-catalyzed transformation was highlighted with a multigram scale synthesis with reduced catalyst loading (Fig. 3b).

a Comparison between rhodaelectro catalysis and Cu(OAc)2·H2O as the chemical oxidant. b Rhodaelectro-catalyzed annulation on multigram scale.

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With the optimized conditions in hand, we explored the scope of salicylic aldehydes 16 (Fig. 4a). Overall, differently substituted aldehydes efficiently furnished the desired products 1836. Especially redox sensitive groups, such as bromo- iodo- and thioether substituents were fully tolerated and delivered the corresponding products 2729. The electron-deficient substrate with an ester substituent under water-free conditions, as well as salicylic aldehyde with an amine functionality were selectively converted to the corresponding chromones 30 and 31, respectively. Even bulky disubstituted aldehydes delivered the desired products 34 and 35 in very good yields. To our delight, also the estrone derivative was converted to the product 37.

a Aldehyde scope for various substituents. b Scope of viable Movavi Screen Capture Studio 9.4.0 Crack + Portable Download. c Calculated energy profiles for the regioselective determining step for the Me/CF3 substituted alkyne at the PW6B95-D3(BJ)/def2-QZVP+SMD(methanol)//PBE0-D3(BJ)/def2-SVP level of theory and spatial localization of noncovalent interactions in the transition states. In the latter, red indicate repulsive interactions, with blue and green being attributed to strong and weak attractive interactions. aWith nBu4NPF6 (0.1 Μ) instead of H2O. b7 h. cRatio determined by 19F-NMR. dWith 5.0 mol 1click dvd copy review - Activators Patch [Cp*RhCl2]2.

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Subsequently, we turned our attention to the viable alkyne 10 scope in greater detail (Fig. 4b). Electron-rich alkynes were efficiently converted to the corresponding chromones 40 and 41. meta- and sterically encumbered ortho-arylalkynes were also tolerated by the rhodaelectro catalysis regime (4245).

Subsequently, a wealth of unsymmetrically substituted alkynes were efficiently converted to the desired products 46–57 (Fig. 4b). Thereby, terminal as well as keto- and amido-substituted alkynes underwent the rhodaelectro catalysis with high efficacy (52–56). As to the regioselectivity of unsymmetrical alkynes, the alkyne substrates furnished chromones 4955 with the aryl motif proximal to the oxygen-heteroatom. Under otherwise identical reaction conditions, alkynes with nitrile, ester or free acid groups provided less satisfactory results. It is noteworthy that hydroxyheptyne (10w) exclusively yielded the regioisomer 57. In order to gain insights into the origin of the regioselectivity for the synthesis of chromone 57, DFT calculations were carried out for the migratory insertion step at the PW6B95-D3(BJ)/def2-QZVP+SMD(methanol)//PBE0-D3(BJ)/def2-SVP level of theory (Supplementary Fig. 22). The transition state leading to regioisomer 57 with the hydroxyl distal to the carbonyl group of the substrate is favored by 2.4 kcal mol−1, which can be attributed to favorable hydrogen bonding interactions with the hydroxyl group in the transition state structure (TS(1-2), Supplementary Fig. 22). Likewise, the regioselectivity of the electrocatalytic C–H activation with 4-methyl-4’-trifluoromethyltolane could be rationalized by DFT computation (Fig. 4c). The calculated regioselectivity was in good agreement with the experimental observations. Here, noncovalent interactions were found to be of minor relevance.

Chemically encoded peptidomimetics reduce enzymatic degradation and feature superior binding affinities, cell permeability, and pharmacokinetics40,41. However, the functionalization of structurally complex peptides mostly rely on terminal peptides, azide-based click chemistry or on the innate reactivity of cysteine42,43,44. Given the practical importance of late-stage peptide diversifications, we became attracted to tyrosine modifications through rhodaelectro catalysis to access tyrosine-derived fluorescent amino acids. Indeed, tyrosines were chemo-selectively annulated with tolane and naphthalene derived alkynes furnishing the desired products 60–62. Next, we probed dipeptides to explore rhodaelectro-catalytic site-specific labeling (Fig. 5a). To our delight, a broad variety of dipeptides was efficiently converted to the corresponding products 63–68. Notably, even oxidation-sensitive serine (65) and methionine (66) containing peptides were transformed to the desired products. Furthermore, potentially coordinating dipeptides with unprotected tryptophan, or tyrosine regioselectively provided the desired products 67 and 68.

a Scope of rhodaelectro-catalyzed peptide labeling. b Photoelectrochemical annulation towards π-extended peptide labels. c Absorption and emission properties of 62 (10 mg/L) and 70 (0.5 mg/L) in CHCl3. d Late-stage functionalization of pentapeptide 71. aWith tAmylOH/H2O (3:1). b7 h. cWith 5.0 mol % of [Cp*RhCl2]2. dWith MeOH instead of EtOH.

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We explored an improvement of the photoelectronic properties of the thus-obtained labels by a late-stage annulation. The aryl moieties were selectively transformed into π-extended peptide labels in a photoelectrochemical process to obtain the desired products (Fig. 5b). Labels 69 and 70 demonstrated improved photoelectronic properties in comparison to the corresponding diaryl precursors 60 and 62 (Fig. 5c and Supplementary Table 2). Since compound 70 exhibited intense fluorescence at 458 nm, it bears considerable potential as a fluorogenic probe45,46.

Finally, we probed our strategy for the functionalization of structurally complex oligopeptide 71. Indeed, peptide 72 was obtained in excellent yield, highlighting the unique power of the rhodaelectro-catalytic labeling strategy (Fig. 5d).

In summary, we have reported on a rhodaelectro-catalyzed transformation of hydroxy-benzaldehydes by electrochemical formyl C–H activation, featuring scalability, high functional group tolerance, and improved efficiency in comparison to chemical oxidants. The strategy proved applicable to the functionalization of tyrosine derivatives, enabling difficult to perform, site-selective electro-labeling of amino acids and peptides by formyl C–H activation. A mediated photoelectrochemical oxidation allowed for an enhancement of fluorescence properties of the thus-obtained amino acids. The rhodaelectro catalysis was inspired by in-depth mechanistic insights, through the isolation and electroanalytical characterization of key intermediates, providing strong support for an oxidation-induced reductive elimination.


Rhodaelectro-catalyzed formyl C–H activation

The electrocatalysis was carried out in an undivided cell, with a graphite felt (GF) anode (25 × 10 × 6.0 mm) and a platinum cathode (25 × 10 × 0.125 mm). The 2-hydroxylbenzaldehyde (0.75 mmol), the alkyne (0.25 mmol), NaOPiv (62 mg, 0.50 mmol), [Cp*RhCl2]2 (3.9 mg, 2.5 mol %), and tAmylOH/H2O (4.0 mL, 3:1) were placed in a 10 mL cell. Electrocatalysis was performed at 100 °C with a constant current of 4 mA maintained for 3.5–7.0 h. Then, the DC-power supply was stopped and the reaction mixture was diluted with EtOAc (2.0 mL). The electrodes were washed with EtOAc (Pt: 1 × 5.0 mL; C: 3 × 10.0 mL). The solvents were combined with the reaction mixture, silica gel was added and the solvents were removed in vacuo. Subsequent column chromatography on silica gel afforded the corresponding products.

Data availability

The authors declare that the data supporting the findings of this study are available within the paper and its supplementary information files. The X-ray crystallographic coordinates for structures reported in this study have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition numbers 2046225, 2046228-2046229, 2046502-2046508. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via All other requests for materials and information should be addressed to the corresponding authors. Source data are provided with this paper.


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Generous support by the DFG (Gottfried-Wilhelm-Leibniz prize) is Internet Download Manager 6.38 Build 22 Crack Registration Download acknowledged. We thank Dr. Christopher Golz (University Göttingen) for the X-ray diffraction analysis.


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  1. Institute for Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Göttingen, Germany

    Maximilian Stangier, Antonis M. Messinis, João C. A. Oliveira, Hao Yu & Lutz Ackermann


M.S. conducted the experimental mechanistic studies, unraveled the rhodaelectro-catalyzed formyl C–H functionalization, and explored the substrate scope, initially assisted by H.Y. A.M.M. isolated and characterized rhodium complexes. J.O. performed the computational studies. L.A. conceived and supervised the project. L.A. and M.S. wrote the manuscript.

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Correspondence to Lutz Ackermann.

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Stangier, M., Messinis, A.M., Oliveira, J.C.A. et al. Rhodaelectro-catalyzed access to chromones via formyl C–H activation towards peptide electro-labeling. Nat Commun12, 4736 (2021).

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