Palladium catalysts help to synthesize key chemicals for many industries. However, the direct reaction of two basic reagents, aryl halides and alkyllithium compounds, remains a challenge. Viktoria H. Gessner, Ruhr-Universität Bochum, Germany, and colleagues have found that a catalyst containing YPhos-type ligands can mediate this reaction even at room temperature. This discovery may contribute to the development of more sustainable processes in the chemical industry.
Pd-Catalyzed Coupling Reactions
Palladium-catalyzed chemical processes are very useful. Palladium catalysts help to couple simple carbon-containing compounds to form more complicated chemical structures. However, so far they have failed to couple two common reagents in chemical synthesis, aryl halides and alkyllithium compounds. Among the aryl halides, aryl chlorides are common reagents that react variably during palladium-catalyzed reactions to produce side products.
For coupling reactions with aryl halides and alkyllithium compounds, chemists usually take “detours” by adding intermediate synthesis steps. Unfortunately, every extra synthesis step produces chemical waste and adds costs.
This problem led the researchers to investigate new palladium catalysts. They thought that a functional catalyst would ease many chemical syntheses. “The coupling of aryl chloride and alkyllithium reagents represents one of the most challenging reactions and—if being successful—promises a broad applicability,” the team explains. After testing various existing catalysts, the researchers identified a promising candidate. This catalyst was based on a class of ylide-substituted phosphines called YPhos.
Chemists use YPhos-containing palladium catalysts for difficult coupling reactions. The YPhos ligands combine a negatively charged carbon center and a positively charged phosphonium group (the ylide) with a phosphine-type ligand. Phosphines are typical ligands in palladium catalysis. This ylide–phosphine ligand setup results in special electronic properties. The scientists observed that the ligand helped to activate aryl halides, which is a crucial step in the reaction between aryl halides and alkyllithium compounds.
One of the YPhos class of ligands, a ligand called joYPhos, was shown to have the most favorable architecture. Its combination of electronic properties and a space-filling architecture suppressed the many side reactions otherwise occurring in the coupling.
The researchers remark that precatalysts containing the YPhos ligands also performed extraordinarily well. Precatalysts have their ligands and a palladium source prearranged in separate compounds. Like two-component adhesives, they assemble in the reaction mixture to form the effective catalyst. This prearrangement makes their handling user-friendly and the compounds are more stable than the free ligands, according to the team.
In a scale-up of the reaction, the scientists synthesized a building block of lesinurad, a drug used for treating gout. They also showed that the catalyst performed well for many variations of the aryl halide and alkyllithium reagents. These results led to the conclusion that this transformation is generally applicable. This new palladium catalyst may, thus, help to avoid costly “detours” in organic syntheses.
- Efficient Pd‐Catalyzed Direct Coupling of Aryl Chlorides with Alkyllithium Reagents,
Viktoria H. Gessner, Thorsten Scherpf, Henning Steinert, Angela Großjohann, Katharina Dilchert, Jens Tappen, Ilja Rodstein,
Angew. Chem. Int. Ed. 2020.
Vichukizo vya palladium husaidia kutengeneza kemikali muhimu kwa viwanda vingi. Hata hivyo, mmenyuko wa moja kwa moja wa reagents mbili za msingi, aryl halides na alkyllithium misombo, bado ni changamoto. Viktoria H. Gessner, Ruhr-Universität Bochum, Ujerumani, na wenzake wamegundua kwamba kichocheo chenye ligandi za aina ya YPhos kinaweza kuingilia mwitikio huu hata katika joto la chumba. Ugunduzi huu unaweza kuchangia maendeleo ya michakato endelevu zaidi katika sekta ya kemikali. Pd-Catalyzed Coupling Reactions Palladium-catalyzed michakato ya kemikali ni muhimu sana. Vichukizo vya palladium husaidia kuunganisha misombo sahili yenye kaboni ili kufanyiza miundo tata zaidi ya kemikali. Hata hivyo, hadi sasa wameshindwa kuunganisha reagents mbili za kawaida katika synthesis ya kemikali, aryl halides na alkyllithium misombo. Miongoni mwa aryl halides, aryl chlorides ni reagents kawaida ambayo kuitikia tofauti wakati wa palladium-catalyzed athari za kuzalisha bidhaa upande. Kwa ajili ya kuunganisha athari na aryl halides na alkylithium misombo, wanakemia kawaida kuchukua <unk>detours<unk> kwa kuongeza hatua za synthesis kati. Kwa kusikitisha, kila hatua ya ziada ya utengenezaji hutokeza taka za kemikali na kuongeza gharama. Tatizo hilo liliwafanya watafiti wachunguze vifaa vipya vya kuchochea nishati ya palladium. Walifikiri kwamba kichocheo cha kazi kingefanya iwe rahisi kutengeneza kemikali nyingi. <unk> Kuunganisha aryl chloride na alkyllithium reagents inawakilisha moja ya athari changamoto zaidi na <unk> kama kuwa na mafanikio <unk> anaahidi matumizi pana, <unk> timu anaelezea. Baada ya kupima vichocheo mbalimbali vilivyopo, watafiti walitambua kichocheo chenye kuahidi. Kichocheo hiki kilitegemea darasa la phosphines zilizobadilishwa na ylide zinazoitwa YPhos. Wanasayansi wa kemikali hutumia YPhos-kujumuisha palladium catalysts kwa majibu magumu ya kuunganisha. YPhos ligands kuchanganya negatively charged carbon kituo na positively charged phosphonium kundi (ylid) na phosphine-aina ligand. Phosphines ni ligands ya kawaida katika catalysis palladium. Hii ylide<unk>phosphine ligand kuanzisha matokeo katika mali maalum ya elektroniki. Liganidi hiyo ilisaidia kuamsha halides ya aryl, hatua muhimu katika athari kati ya halides za aryl na misombo ya alkyllithium. Moja ya darasa la YPhos la ligands, ligand inayoitwa joYPhos, ilionyeshwa kuwa na usanifu mzuri zaidi. Mchanganyiko wake wa mali za elektroniki na usanifu wa kujaza nafasi ulikandamiza athari nyingi za upande ambazo zingeweza kutokea katika kuunganisha. Watafiti wanasema kwamba precatalysts zenye YPhos ligands pia alifanya ajabu vizuri. Precatalysts kuwa ligands yao na chanzo palladium prearranged katika misombo tofauti. Kama adhesives mbili-kiungo, wao kukusanya katika mchanganyiko wa athari ya kuunda kichocheo ufanisi. Mpangilio huu wa awali hufanya utunzaji wao uwe wa kirafiki na misombo ni thabiti zaidi kuliko ligands huru, kulingana na timu. Katika hatua ya kwanza, wanasayansi walifanya lesinuradi, dawa inayotumiwa kutibu ugonjwa wa gout. Pia walionyesha kwamba kichocheo hicho kilifanya vizuri kwa tofauti nyingi za aryl halide na reagents za alkyllithium. Matokeo haya yalisababisha hitimisho kwamba mabadiliko haya ni ya kawaida kutumika. Kwa hiyo, kichocheo hiki kipya cha palladium kinaweza kusaidia kuepuka "njia za kugeuka" zenye gharama kubwa katika utengenezaji wa kikaboni. - Efficient Pd-Catalyzed Direct Coupling of Aryl Chlorides with Alkyllithium Reagents, Viktoria H. Gessner, Thorsten Scherpf, Henning Steinert, Angela Großjohann, Katharina Dilchert, Jens Tappen, Ilja Rodstein, Angew. Kem. Int. Ed. - Ed. - Ed. Mwaka wa 2020.