Speciality Chemicals Magazine JAN / FEB 2025 | Page 26

CATALYSTS
catalysed cyclopropanation , allowing the production of a 205 kg batch with an inexpensive and readily available starting material . Fe ( acac ) 3
-catalysed Grignard reactions for the multi-kilo syntheses of both a heterocyclic dual
NK 1
/ serotonin receptor antagonist ( 8 ) and a calcium-sensing receptor antagonist ( 9 ).
The Parkinson treatment drug candidate MCL-509 ( 10 ) is synthesised on a large scale by the use of a non-classical Polonovski reaction catalysed by Fe / HCl / FeCl 3 · 6H 2
O . The manufacture of the proteasome inhibitor carfilzomib ( 11 ) involves a kilogram-scale asymmetric epoxidation catalysed by manganese . Continuous flow is also a growing area of pharma development that can increase reaction efficiency . At Lilly , a multi-kilo scale continuous flow Chan-Lam coupling was catalysed by Cu ( OAc ) 2
/ bipyridine for the production of an API intermediate ( 12 ).
Promising developments
The field of non-PGM catalysis is still young and full of potential , and many promising discoveries and advances have been made recently ( Figure 3 ). Researchers at MIT developed a copper-catalysed amination of aryl chlorides using a highly sterically hindered ligand ( 13 ) to prevent catalyst deactivation . New copper ligands in recent discoveries include oxalic diamides ( 14 ) and picolinamides ( 15 ).
Chemists at Pfizer showed that 6-hydroxypicolinamide ( 16 ) is an effective copper ligand for the C-N
Figure 3 - Selected recently reported catalysts and ligands for non-PGM catalysis
coupling of heteroaryl primary amines and heteroaryl bromides . Other developments improve on already well-known ligands : the common copper ligand trans-CyDMEDA , which is an oil , can be replaced by its much easier-to-handle MSA salt ( 17 ), which is a solid , in C-N coupling reactions .
In nickel catalysis , new precatalysts have been developed and applied to many useful reactions . Ni ( TMEDA ) ( o-tolyl ) Cl ( 18 ) has been used in multiple named reactions , including Suzuki-Miyaura , Buchwald-Hartwig , Kumada , Negishi and Heck . Ni ( COD ) ( DQ ) ( 19 ) is a precatalyst for C-C , C-N and C-B bond formations with good yields . In other reactions , ligands traditionally used for palladium catalysis can also be used for nickel catalysis , such as the application of DPEPhos to nickel-catalysed Suzuki- Miyaura couplings .
Another prominent class of nickel precatalysts is the PAd-DalPhos family of catalysts , of which Ni ( NHP-DalPhos ) ( o-tol ) Cl ( 20 ). This type of bis-phosphine ligands has been successfully applied in a wide range of challenging C-C , C-N and C-O bond formation reactions .
Industrial pharmaceutical development of these discoveries is worthy of attention by process chemists , as shown by many large-scale implementations . Non-PGM catalysis will never fully replace PGM catalysis , but should always be evaluated in parallel as a complementary technology . ●
J j
Sinocompound
sales @ sinocompound . com en . sinocompound . com
References : 1 : D . C . Elliott , Chemicals from Biomass , in Encyclopedia of Energy , Elsevier , Amsterdam , 2004 , Vol . 1 , 163−174 2 : E . Baraj , K . Ciahotný , & T . Hlinčik . Fuel 2021 , 288 , 119817 3 : C . A . Tolman et . al , Adv . Catal . 1985 , 33 , 1−46 4 : B . Yang , J . He , G . Zhang , J . Guo , Chapter 15 – Vanadium Catalysts , in Vanadium , Elsevier , 2021 ; pp 415−443 5 : Y . Liu , P . Li , Y . Wang & Y . Qiu . Angew . Chem . Int . Ed . 2023 , 62 ( 45 ), e202306679 6 : M . B . Peoples , et al . Chapter 8 , in The Contributions of Legumes to Reducing the Environmental Risk of Agricultural Production , Agroecosystem Diversity , Academic Press , 2019 , 123−143 7 : H . Zhao , A . K . Ravn , M . C . Haibach . K . M . Engle & C . C . C . J . Seechurn , ACS Catal . 2024 , 14 , 13 , 9708 – 9733
8 : F . Peng et al . J . Org . Chem . 2016 , 81 ( 20 ), 10009−10015 9 : Q . Tian et al . Org . Process Res . Dev . 2013 , 17 ( 1 ), 97−107 10 : S . K . Nimmagadda et al . Org . Process Res . Dev . 2020 , 24 ( 6 ), 1141−1148 11 : M . C . Haibach et al . Chem . Sci . 2022 , 13 ( 43 ), 12906−12912 12 : W . P . Gallagher et al . Org . Process Res . Dev . 2017 , 21 ( 8 ), 1156−1165 13 : F . Peng et al . Org . Process Res . Dev . 2020 , 24 ( 11 ), 2453−2461 14 : R . O . Cann et al . Org . Process Res . Dev . 2010 , 14 ( 5 ), 1147−1152 15 : A . F . Baldwin et al . Org . Process Res . Dev . 2021 , 25 ( 4 ), 1065−1073 16 : J . S . Hartung , N . Greszler , R . C . Klix & J . M . Kallemeyn , Org . Process Res . Dev . 2019 , 23 ( 11 ), 2532−2537
17 : R . F . Algera et al . Org . Process Res . Dev . 2023 , 27 ( 12 ), 2260−2270 18 : C . Risatti , K . J . Natalie , Z . Shi & D . A . Conlon , Org . Process Res . Dev . 2013 , 17 ( 2 ), 257−264 19 : N . Tewari , N . Maheshwari , R . Medhane , H . Nisar & M . Prasad , Org . Process Res . Dev . 2012 , 16 ( 9 ), 1566−1568 20 : A . M . Ruda , S . Papadouli , V . Thangavadivale & J . D . Moseley , Org . Process Res . Dev . 2022 , 26 ( 5 ), 1398−1404 21 : P . K . Dornan et al . Org . Process Res . Dev . 2020 , 24 ( 4 ), 481−489 ; M . G . Beaver , et al . Org . Process Res . Dev . 2020 , 24 ( 4 ), 490−499 ; A . J . Maloney et al . Org . Process Res . Dev . 2020 , 24 ( 10 ), 1891−1908 22 : A . Campbell Brewer et al . Org . Process Res . Dev . 2019 , 23 ( 8 ), 1484−1498 23 : H . J . Ai , S . T . Kim , C . Liu & S . L . Buchwald , J . Am . Chem . Soc . 2024 , 146 , 25949−25955
24 : W . Zhou , M . Fan , J . Yin , Y . Jiang & D . Ma , J . Am . Chem . Soc . 2015 , 137 , 11942−11945 25 : D . J . Bernhardson , D . W . Widlicka & R . A . Singer , Org . Process Res . Dev . 2019 , 23 , 1538−1551 26 : P . E . Maligres , S . W . Krska & P . G . Dormer , J . Org . Chem . 2012 , 77 , 7646−7651 27 : J . Magano & S . Monfette , ACS Catal . 2015 , 5 , 3120−3123 28 : V . T . Tran , Z . Q . Li , O . Apolinar , J . Derosa , M . Joannou , S . R . Wisniewski , M . D . Eastgate & K . M . Engle , Angew . Chem . Int . Ed . 2020 , 59 , 7409−7413 29 : R . S . Sawatzky , M . J . Ferguson & M . Stradiotto , Synlett 2017 , 28 , 1586−1591 ; R . S . Sawatzky , M . Stradiotto , Synlett 2018 , 29 , 799−804 ; P . H . Gehrtz , V . Geiger , T . Schmidt , L . Srsan & I . Fleischer , Org . Lett . 2019 , 21 , 50−55 30 : K . M . Morrison & M . Stradiotto , Chem . Sci . 2024 , 15 , 7394−7407
26 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981