Coupling runs across water and DES: Scalable Pd‐catalyzed Negishi cross‐couplings between (hetero)aryl bromides and organozinc halides have been developed either by using bulk water, or the choline chloride/urea eutectic mixture as a reaction medium. These processes proceed under mild conditions, short reaction times in air, in the absence of additional ligands, with high chemoselectivity and a broad substrate scope.
Abstract
Pd‐catalyzed Negishi cross‐coupling reactions between organozinc compounds and (hetero)aryl bromides have been reported when using bulk water as the reaction medium in the presence of NaCl or the biodegradable choline chloride/urea eutectic mixture. Both C(sp3)‐C(sp2) and C(sp2)‐C(sp2) couplings have been found to proceed smoothly, with high chemoselectivity, under mild conditions (room temperature or 60 °C) in air, and in competition with protonolysis. Additional benefits include very short reaction times (20 s), good to excellent yields (up to 98 %), wide substrate scope, and the tolerance of a variety of functional groups. The proposed novel protocol is scalable, and the practicability of the method is further highlighted by an easy recycling of both the catalyst and the eutectic mixture or water.
https://ift.tt/2Q4GExe
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c04690
https://ift.tt/2XPhELA
Ylide‐functionalized phosphines were tailored to fit the requirements of room‐temperature Negishi couplings of aryl chlorides. YPhos/Pd catalyst is highly efficient for the coupling with aryl chlorides in general, and the reaction shows excellent functional group compatibility. This allows the selective coupling of aryl electrophiles in the competitive reaction as demonstrated in the synthesis of ibuprofen.
Abstract
The coupling of aryl chlorides with Reformatsky reagents is a desirable strategy for the construction of α‐aryl esters but has so far been substantially limited in the substrate scope due to many challenges posed by various possible side reactions. This limitation has now been overcome by the tailoring of ylide‐functionalized phosphines to fit the requirements of Negishi couplings. Record‐setting activities were achieved in palladium‐catalyzed arylations of organozinc reagents with aryl electrophiles using a cyclohexyl‐YPhos ligand bearing an ortho‐tolyl‐substituent in the backbone. This highly electron‐rich, bulky ligand enables the use of aryl chlorides in room temperature couplings of Reformatsky reagents. The reaction scope covers diversely functionalized arylacetic and arylpropionic acid derivatives. Aryl bromides and chlorides can be converted selectively over triflate electrophiles, which permits consecutive coupling strategies.
https://ift.tt/3i427R5
The metal‐catalyzed cross‐coupling of organozinc reagents has been studied since its discovery in 1977, but the dramatic dependence on salt additives was only realized some 30 years later. LiCl and LiBr have been found not only to improve coupling outcomes, but their absence can shut down the reaction completely. This Review summarizes all reports outlining the ways that salt additives impact the formation of organozinc reagents and their use in Negishi cross‐coupling.
Abstract
The first cross‐coupling of organozinc nucleophiles with aryl halides was reported in 1977 by Negishi. Unknown to all at the time was the importance of salt additives that were often present as a byproduct from the organozinc preparation. For decades, these salt additives were overlooked until 2006 when it was discovered that two different, yet effective methods for preparing organozinc solutions (i.e. one with salt and one without) provided drastically different results. Since this finding, the exact role of salt additives in cross‐coupling has been debated in the catalysis community. In this Review we highlight all the major discoveries regarding the influence of salt additives on the formation of organozinc reagents and their use in the Negishi reaction. These effects include solubilizing key intermediates, the formation of higher‐order zincates, product inhibition, catalyst protection, and solvent effects.
https://ift.tt/339OslJ
The funeral director was asking us what we think Mum should wear in her casket.
Mum always loved to wear sarongs (fabric wraps that go around the torso and drape downward a bit like a long skirt would), so my uncle suggested that she wear a sarong in there.
The funeral director looked a bit confused, as did some of our family members, to which my uncle added:
"What's sarong with that?"
I started laughing like an idiot. He was proud of it too. The funeral director was rather shocked. We assured her, and our more proper relatives, that Mum would've absolutely loved the joke (which is very true).
His delivery was perfect. I'll never forget the risk he took. We sometimes recall the moment as a way help cushion the blows of the grieving process.
--Edit-- I appreciate the condolences. I'm doing well and the worst is behind me and my family. But thanks :)
--Edit-- Massive thanks for all the awards and kind words. And the puns! Love 'em.
I would have a daughter
Capital of Ireland
It's Dublin everyday
But Bill kept the Windows
True story; it even happened last night. My 5-year-old son walks up behind me and out of the blue says, "hey."
I turn to him and say, "yeah, kiddo? What's up?"
He responds, "it's dead grass."
I'm really confused and trying to figure out what's wrong and what he wants from me. "What? There's dead grass? What's wrong with that?"
.
.
.
He says, totally straight-faced, "hay is dead grass," and runs off.
You officially hit rock bottom
http://m.imgur.com/ImM3RWz
And then you will all be sorry.
Now it’s syncing.
He replied, "Well, stop going to those places then!"
I will find you. You have my Word.
She said how do you know he was headed to work?
“thank you for your cervix.”
...sails are going through the roof.
Made me smile
Mods said I'm a cereal reposter...
A taxi
But now I stand corrected.
Wait. Sorry, wrong sub.
Wookie mistake.
Theoretical Fizz-ics
Because you can’t ‘C’ in the dark
Pd‐catalyzed Negishi cross‐coupling reactions between organozinc compounds and (hetero)aryl bromides have been reported when using bulk water as the reaction medium in the presence of NaCl or the biodegradable choline chloride/urea eutectic mixture. Both C(sp 3 )–C(sp 2 ) and C(sp 2 )–C(sp 2 ) couplings have been found to proceed smoothly, with high chemoselectivity, under mild conditions (room temperature or 60°C) in air, and in competition with protonolysis. Additional benefits include very short reaction times (20 s), good to excellent yields (up to 98%), wide substrate scope, and the tolerance of a variety of functional groups. The proposed novel protocol is scalable, and the practicability of the method is further highlighted by an easy recycling of both the catalyst and the eutectic mixture or water.
https://ift.tt/3dtLuOg
The coupling of aryl chlorides with Reformatsky reagents is a desirable strategy for the construction of α‐aryl esters but has so far been substantially limited in the substrate scope due to many challenges posed by various possible side reactions. This limitation has now been overcome by the tailoring of ylide‐functionalized phosphines to fit the requirements of Negishi couplings. Record‐setting activities were achieved in palladium‐catalyzed arylations of organozinc reagents with aryl electrophiles using a cyclohexyl‐YPhos ligand bearing an ortho ‐tolyl‐substituent in the backbone. This highly electron‐rich, bulky ligand enables the use of aryl chlorides in room temperature couplings of Reformatsky reagents. The reaction scope covers diversely functionalized arylacetic and arylpropionic acid derivatives. Aryl bromides and chlorides can be converted selectively over triflate electrophiles, which permits consecutive coupling strategies.
https://ift.tt/3i427R5
