Final Report Summary - ALCO2HOL (Chasing sustainability: Synthesis of carboxylic acids from simple alcohols via CO2 fixation)
Abstract
One of the most fundamental gaps in catalysis is the use of alternative feedstocks such as carbon dioxide (CO2) to produce chemicals. Conducting basic and fundamental research by making chemicals from CO2 while maximizing the yield and not generating waste will be an important move towards the development of “perfect chemical reactions”. In this regard, ALCO2HOL has provided with novel routes to the insertion of CO2 into organic frameworks in an innovative and challenging manner, thus opening up new concepts in catalysis and enhancing ever-growing quality of the European research.
State-of-the-art
Ideally, the ultimate goal in catalysis would be the use of unfunctionalized, abundant, unreactive and inert molecular entities such as C–H, C–C or C–O bonds, thus lowering the overall cost for producing fine-chemicals. Despite the advances realized, particularly in the field of C–H activation, these methodologies are unfortunately not attractive for our chemical industry because of atom efficiency: they generate a considerable amount of waste as consequence of using stoichiometric amounts of salts, additives, oxidants or the use of prefunctionalized substrates. These drawbacks are particularly important, as sustainable development is an issue that must no longer be ignored by our society. As global demand and prices for petroleum-based feedstocks continue to rise, chemists are being challenged to devise processes that utilize biomass-derived feedstocks, such as carbon dioxide (CO2).
In this regard, ALCO2HOL project has contributed to science by providing novel routes for the synthesis of carboxylic acids via the insertion of CO2 into organic matter. Carboxylic acids are relevant functionalities present in a wide variety of biologically active compounds as well as pharmaceuticals (Scheme 1). For example, Atorvastatin (high cholesterol levels), Beraprost (vasodilatator) or Pregabalin (anticonvulsant) are blockbuster drug which contain the carboxylic acid moiety in their core.
ALCO2HOL steed out from the need to develop sustainable methods for the obtention of such carboxylic acids by simply using alcohol derivatives and CO2 as starting materials. As a consequence, ALCO2HOL has successfully demonstrated the possibility of carboxylating tremendously challenging substrates such as alkyl bromides and alkyl alcohol derivatives (Scheme 1) by means of nickel catalysis.
A wide variety of substrates were amenable for carboxylation and therefore, introducing a carboxylic acid directly from CO2. As shown in Scheme 2, rather structurally complex molecules smoothly reacted with CO2 to obtain the corresponding carboxylic acids.
Similarly to the primary alkyl halides and alcohol derivatives, we also developed a methodology for the obtention of allyl carboxylic acids. The methodology developed however has the potential of obtaining the regiosiomer of choice simply by choosing the appropriate ligand for the catalyst (Scheme 3).
In this regioselective nickel-catalyzed carboxylation of allyl acetates, a wide variety of functionalities were also tolerated thus showcasing the robustness of our protocol.
In summary, we have contributed to the development of novel methodologies based on Nickel catalysis form the insertion of CO2 into organic matter. ALCO2HOL project has allowed for the first time, the introduction of CO2 into alkyl moieties by means of catalysis. Moreover, It opened the door to other strategies such as the regioselective insertion of CO2 into simple allyl alcohol derivatives such as allyl acetates.
The impact of these methodologies is reflected in the publication of 2 scientific reports in a high-ranked journal. Although early for industrial implementation at large scale, this methods open the door to envisage novel methodologies based on catalytic amounts of metal for the insertion of CO2 into organic matter. If possible in the near future, it would be of great importance for placing carbon dioxide as a common C1 feedstock to our current petroleum based palette.
References:
- Ni-catalyzed Carboxylation of Unactivated Primary Alkyl Bromides and Sulfonates with CO2. Liu, Y.; Cornella, J.; Martin, R. J. Am. Chem. Soc. 2014, 136, 11212.
- Ligand-controlled Regiodivergent Ni-catalyzed Reductive Carboxylation of Allyl Esters with CO2. Cornella, J.; Moragas, T.; Martin, R. J. Am. Chem. Soc. 2014, 136, 17702
One of the most fundamental gaps in catalysis is the use of alternative feedstocks such as carbon dioxide (CO2) to produce chemicals. Conducting basic and fundamental research by making chemicals from CO2 while maximizing the yield and not generating waste will be an important move towards the development of “perfect chemical reactions”. In this regard, ALCO2HOL has provided with novel routes to the insertion of CO2 into organic frameworks in an innovative and challenging manner, thus opening up new concepts in catalysis and enhancing ever-growing quality of the European research.
State-of-the-art
Ideally, the ultimate goal in catalysis would be the use of unfunctionalized, abundant, unreactive and inert molecular entities such as C–H, C–C or C–O bonds, thus lowering the overall cost for producing fine-chemicals. Despite the advances realized, particularly in the field of C–H activation, these methodologies are unfortunately not attractive for our chemical industry because of atom efficiency: they generate a considerable amount of waste as consequence of using stoichiometric amounts of salts, additives, oxidants or the use of prefunctionalized substrates. These drawbacks are particularly important, as sustainable development is an issue that must no longer be ignored by our society. As global demand and prices for petroleum-based feedstocks continue to rise, chemists are being challenged to devise processes that utilize biomass-derived feedstocks, such as carbon dioxide (CO2).
In this regard, ALCO2HOL project has contributed to science by providing novel routes for the synthesis of carboxylic acids via the insertion of CO2 into organic matter. Carboxylic acids are relevant functionalities present in a wide variety of biologically active compounds as well as pharmaceuticals (Scheme 1). For example, Atorvastatin (high cholesterol levels), Beraprost (vasodilatator) or Pregabalin (anticonvulsant) are blockbuster drug which contain the carboxylic acid moiety in their core.
ALCO2HOL steed out from the need to develop sustainable methods for the obtention of such carboxylic acids by simply using alcohol derivatives and CO2 as starting materials. As a consequence, ALCO2HOL has successfully demonstrated the possibility of carboxylating tremendously challenging substrates such as alkyl bromides and alkyl alcohol derivatives (Scheme 1) by means of nickel catalysis.
A wide variety of substrates were amenable for carboxylation and therefore, introducing a carboxylic acid directly from CO2. As shown in Scheme 2, rather structurally complex molecules smoothly reacted with CO2 to obtain the corresponding carboxylic acids.
Similarly to the primary alkyl halides and alcohol derivatives, we also developed a methodology for the obtention of allyl carboxylic acids. The methodology developed however has the potential of obtaining the regiosiomer of choice simply by choosing the appropriate ligand for the catalyst (Scheme 3).
In this regioselective nickel-catalyzed carboxylation of allyl acetates, a wide variety of functionalities were also tolerated thus showcasing the robustness of our protocol.
In summary, we have contributed to the development of novel methodologies based on Nickel catalysis form the insertion of CO2 into organic matter. ALCO2HOL project has allowed for the first time, the introduction of CO2 into alkyl moieties by means of catalysis. Moreover, It opened the door to other strategies such as the regioselective insertion of CO2 into simple allyl alcohol derivatives such as allyl acetates.
The impact of these methodologies is reflected in the publication of 2 scientific reports in a high-ranked journal. Although early for industrial implementation at large scale, this methods open the door to envisage novel methodologies based on catalytic amounts of metal for the insertion of CO2 into organic matter. If possible in the near future, it would be of great importance for placing carbon dioxide as a common C1 feedstock to our current petroleum based palette.
References:
- Ni-catalyzed Carboxylation of Unactivated Primary Alkyl Bromides and Sulfonates with CO2. Liu, Y.; Cornella, J.; Martin, R. J. Am. Chem. Soc. 2014, 136, 11212.
- Ligand-controlled Regiodivergent Ni-catalyzed Reductive Carboxylation of Allyl Esters with CO2. Cornella, J.; Moragas, T.; Martin, R. J. Am. Chem. Soc. 2014, 136, 17702
