Current Research Projects
New Nickel Catalysts
Cross-couplings catalysed by transition metals have evolved to now play a vital role in organic synthesis. The use of nickel catalysts in these pivotal bond-forming reactions is an attractive and often effective alternative to the more popular and expensive palladium counterparts. This research project enabled the formation of a stable Ni(0) alternative to the Ni(cod)2 and phosphine catalytic system. In our investigation (dppf)Ni[P(OPh)3]2 was prepared, without the use of Ni(cod)2, and the complex was used in a series of C-N amination reactions of various aryl chlorides and bromides with anilines or amines. We have used a Ni[P(Op-tolyl)3]4 and Xantphos system for C-S bond formation of electronically diverse aryl/heteroaryl chlorides which are unreactive under standard conditions. In 2020, the Nickel Phosphite system was expanded to include NHC ligands in order to facilitate Suzuki-Miyaura Cross-Coupling. This zerovalent tricoordinate nickel NHC/phosphite complex offers unique reactivity through first loss of a single phosphite ligand.
Cross-couplings catalysed by transition metals have evolved to now play a vital role in organic synthesis. The use of nickel catalysts in these pivotal bond-forming reactions is an attractive and often effective alternative to the more popular and expensive palladium counterparts. This research project enabled the formation of a stable Ni(0) alternative to the Ni(cod)2 and phosphine catalytic system. In our investigation (dppf)Ni[P(OPh)3]2 was prepared, without the use of Ni(cod)2, and the complex was used in a series of C-N amination reactions of various aryl chlorides and bromides with anilines or amines. We have used a Ni[P(Op-tolyl)3]4 and Xantphos system for C-S bond formation of electronically diverse aryl/heteroaryl chlorides which are unreactive under standard conditions. In 2020, the Nickel Phosphite system was expanded to include NHC ligands in order to facilitate Suzuki-Miyaura Cross-Coupling. This zerovalent tricoordinate nickel NHC/phosphite complex offers unique reactivity through first loss of a single phosphite ligand.
|
|
Representative Publications:
1. J. Duczynski, A. N. Sobolev, S. A. Moggach, R. Dorta, S. G. Stewart, The Synthesis and Catalytic Activity of New Mixed NHC-Phosphite Nickel(0) Complexes, Organometallics 2020, 39, 105-115.
2. K D. Jones, D. J. Power, D. Bierer, K M. Gericke, S G. Stewart. Nickel Phosphite/Phosphine-Catalyzed C–S Cross-Coupling of Aryl Chlorides and Thiols, Org. Lett., 2018, 20 , 208–211.
3. S. S. Kampmann; A. N. Sobolev; G. A. Koutsantonis; S. G. Stewart; Stable Nickel(0) Phosphites as Catalysts for C-N Cross Coupling Reactions, Adv. Synth. Catal., 2014, 356, 1967–1973.
1. J. Duczynski, A. N. Sobolev, S. A. Moggach, R. Dorta, S. G. Stewart, The Synthesis and Catalytic Activity of New Mixed NHC-Phosphite Nickel(0) Complexes, Organometallics 2020, 39, 105-115.
2. K D. Jones, D. J. Power, D. Bierer, K M. Gericke, S G. Stewart. Nickel Phosphite/Phosphine-Catalyzed C–S Cross-Coupling of Aryl Chlorides and Thiols, Org. Lett., 2018, 20 , 208–211.
3. S. S. Kampmann; A. N. Sobolev; G. A. Koutsantonis; S. G. Stewart; Stable Nickel(0) Phosphites as Catalysts for C-N Cross Coupling Reactions, Adv. Synth. Catal., 2014, 356, 1967–1973.
Domino Reactions
Domino Reactions have provided effective methods for the synthesis of a range of simple to complex molecules. A domino reaction is defined as "the execution of two or more bond-forming transformations under identical reaction conditions, in which the latter transformations take place at the functionalities formed by the preceding transformation." Several projects have involved the formation of N-heterocycles through domino reactions including, Heck-/aza-Michael Reactions, Tsuji-Trost/Heck Reactions, Alkyne addition/CO insertion/Acylation and Buchwald Hartwig/Heck reactions.
Domino Reactions have provided effective methods for the synthesis of a range of simple to complex molecules. A domino reaction is defined as "the execution of two or more bond-forming transformations under identical reaction conditions, in which the latter transformations take place at the functionalities formed by the preceding transformation." Several projects have involved the formation of N-heterocycles through domino reactions including, Heck-/aza-Michael Reactions, Tsuji-Trost/Heck Reactions, Alkyne addition/CO insertion/Acylation and Buchwald Hartwig/Heck reactions.
Representative Publications:
1. K. D. Jones, M. J. Nutt, E. Comninos, A. N. Sobolev, S. A. Moggach, T. Miura, M. Murakami, S. G. Stewart, A One-Pot Reaction of α-Imino Rhodium Carbenoids and Halohydrins: Access to 2,6-Substituted Dihydro-2H-1,4-oxazines Org Lett, 2020, 22, 3490-3494.
2. J. E. Rixson, B. W. Skelton, G. A. Koutsantonis, K. M. Gericke, and S. G. Stewart, Domino Reactions for the Synthesis of Anthrapyran-2-ones and the Total Synthesis of the Natural Product (±)-BE-26554A, Org Lett, 2013, 4834–4837.
3. J. E. Rixson, T. Chaloner, C. H. Heath, L. F. Tietze, S. G. Stewart, The Development of Domino Reactions Incorporating the Heck Reaction: The Formation of N-Heterocycles, Eur. J. Org. Chem, 2012, 544-558.
4. D. L. Priebbenow, L. C. Henderson, F. M. Pfeffer, S. G. Stewart, Domino Heck-aza-Michael reactions; efficient access to 1-substituted tetrahydro-β-carbolines, J. Org. Chem. 2010, 1787-1790.
5. S. G. Stewart, C. H. Heath, E. L. Ghisalberti, Domino or Single-Step Tsuji–Trost/Heck Reactions and their Application in the Synthesis of 3-Benzazepines and Azepino[4,5-b]indole Ring Systems, Eur. J. Org. Chem, 2009, 1934.
1. K. D. Jones, M. J. Nutt, E. Comninos, A. N. Sobolev, S. A. Moggach, T. Miura, M. Murakami, S. G. Stewart, A One-Pot Reaction of α-Imino Rhodium Carbenoids and Halohydrins: Access to 2,6-Substituted Dihydro-2H-1,4-oxazines Org Lett, 2020, 22, 3490-3494.
2. J. E. Rixson, B. W. Skelton, G. A. Koutsantonis, K. M. Gericke, and S. G. Stewart, Domino Reactions for the Synthesis of Anthrapyran-2-ones and the Total Synthesis of the Natural Product (±)-BE-26554A, Org Lett, 2013, 4834–4837.
3. J. E. Rixson, T. Chaloner, C. H. Heath, L. F. Tietze, S. G. Stewart, The Development of Domino Reactions Incorporating the Heck Reaction: The Formation of N-Heterocycles, Eur. J. Org. Chem, 2012, 544-558.
4. D. L. Priebbenow, L. C. Henderson, F. M. Pfeffer, S. G. Stewart, Domino Heck-aza-Michael reactions; efficient access to 1-substituted tetrahydro-β-carbolines, J. Org. Chem. 2010, 1787-1790.
5. S. G. Stewart, C. H. Heath, E. L. Ghisalberti, Domino or Single-Step Tsuji–Trost/Heck Reactions and their Application in the Synthesis of 3-Benzazepines and Azepino[4,5-b]indole Ring Systems, Eur. J. Org. Chem, 2009, 1934.
Natural Product Synthesis
Several secondary metabolites have been targeted and prepared within the Stewart group. The indole alkaloids Ajamalicine and Arboflorine have been targeted due to their synthetically challenging ring systems and stereochemistry as well as biological activity. The Antrodins, and natural products from the parasitic fungus which has been used in traditionl Chinese medicine Antrodia Camphorata, were prepared and investigated for their activity in liver cancer cell lines. Recently a series of anthracenone-pyranone natural products have been prepared. These compounds are currently being evaluated for their anti-bacterial and anti-tumour growth properties.
Several secondary metabolites have been targeted and prepared within the Stewart group. The indole alkaloids Ajamalicine and Arboflorine have been targeted due to their synthetically challenging ring systems and stereochemistry as well as biological activity. The Antrodins, and natural products from the parasitic fungus which has been used in traditionl Chinese medicine Antrodia Camphorata, were prepared and investigated for their activity in liver cancer cell lines. Recently a series of anthracenone-pyranone natural products have been prepared. These compounds are currently being evaluated for their anti-bacterial and anti-tumour growth properties.
Representative Publications:
1. K. D. Jones, M. J. Nutt, E. Comninos, A. N. Sobolev, S. A. Moggach, T. Miura, M. Murakami, S. G. Stewart, A One-Pot Reaction of α-Imino Rhodium Carbenoids and Halohydrins: Access to 2,6-Substituted Dihydro-2H-1,4-oxazines Org Lett, 2020, 22, 3490-3494.
2. J. E. Rixson, B. W. Skelton, G. A. Koutsantonis, K. M. Gericke, and S. G. Stewart, Domino Reactions for the Synthesis of Anthrapyran-2-ones and the Total Synthesis of the Natural Product (±)-BE-26554A, Org Lett, 2013, 4834–4837.
3. S. G. Stewart, L. A. Ho, M. E. Polomska, A. T. Percival, G. C. T. Yeoh, The rapid evaluation of Antrodia camphorata natural products and derivatives in tumorigenic liver progenitor cells using a novel cell proliferation assay. ChemMedChem, 2009, 4, 1657.
4. S. G. Stewart, C. H. Heath, E. L. Ghisalberti, Domino or Single-Step Tsuji–Trost/Heck Reactions and their Application in the Synthesis of 3-Benzazepines and Azepino[4,5-b]indole Ring Systems, Eur. J. Org. Chem, 2009, 1934.
1. K. D. Jones, M. J. Nutt, E. Comninos, A. N. Sobolev, S. A. Moggach, T. Miura, M. Murakami, S. G. Stewart, A One-Pot Reaction of α-Imino Rhodium Carbenoids and Halohydrins: Access to 2,6-Substituted Dihydro-2H-1,4-oxazines Org Lett, 2020, 22, 3490-3494.
2. J. E. Rixson, B. W. Skelton, G. A. Koutsantonis, K. M. Gericke, and S. G. Stewart, Domino Reactions for the Synthesis of Anthrapyran-2-ones and the Total Synthesis of the Natural Product (±)-BE-26554A, Org Lett, 2013, 4834–4837.
3. S. G. Stewart, L. A. Ho, M. E. Polomska, A. T. Percival, G. C. T. Yeoh, The rapid evaluation of Antrodia camphorata natural products and derivatives in tumorigenic liver progenitor cells using a novel cell proliferation assay. ChemMedChem, 2009, 4, 1657.
4. S. G. Stewart, C. H. Heath, E. L. Ghisalberti, Domino or Single-Step Tsuji–Trost/Heck Reactions and their Application in the Synthesis of 3-Benzazepines and Azepino[4,5-b]indole Ring Systems, Eur. J. Org. Chem, 2009, 1934.