The aim of our research is to develop new selective methods for organic synthesis enabling the preparation of organic compounds with well-defined three-dimensional structures. To achieve this, we design new selective catalysts based on transition metals, which we apply in asymmetric synthesis, and develop new enantioselective catalytic processes. Ongoing projects include:
Lewis acid-Lewis base catalyzed reactions:
Our Lewis acid - Lewis base catalyzed cyanations of aldehydes using ketonitriles to yield, in one step, highly enantioenriched acylated cyanohydrins in high yields are recent important achievements. The new process is fairly general in that a large variety of aldehydes and ketonitriles can be used. The products, which are obtained with perfect atom economy, serve as important synthetic building blocks and have in themselves useful applications as e g environmentally friendly insecticides and herbicides. Recent publications: S. Lundgren, E. Wingstrand, M. Penhoat and C. Moberg, C. J. Am. Chem. Soc. 2005, 127, 11592; S. Lundgren, E. Wingstrand and C. Moberg, Adv. Synth. Catal., 2007, 349, 364; E. Wingstrand, L. Fei, S. Lundgren, M. Penhoat and C. Moberg, Chem. Oggi, 2007, Suppl to Vol 25, no 5, 14.
Secondary interactions: M…H-O hydrogen bond:
During studies of palladium catalyzed asymmetric allylic alkylations we found evidence for a hydrogen bond where Pd(0) serves as the proton acceptor. The presence of this hydrogen bond has major consequences for the stereochemistry of the catalytic process since the conformation of the ligand is affected by the interaction. For this reason ligands with suitably situated hydroxy groups and their O-alkylated analogues exhibit different stereochemical preferences. This is the first example where this type of interaction has consequences for the stereochemistry of a catalytic reaction. DFT computations have verified our conclusions (K. Hallman, T. Wondimagegn, A. Frölander, M. Svensson and C. Moberg, Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5400; A. Frölander, S. Lutsenko, T. Privalov and C. Moberg, J. Org. Chem. 2005, 70, 9882)
We have explored the influence of symmetry, in particular C3 symmetry, in asymmetric reactions. Major experimental studies are based on chiral TREN (tris(2-aminoethyl)amine) derivatives, obtained via our ring opening of chiral aziridines by ammonia. A conceptual survey of C3 symmetry has been published: C. Moberg, Angew. Chem.1998, 37, 248. Other publications: C. Moberg, Angew. Chem.,Int. Ed. 2006, 45, 4721; E. Brulé, Y. Pei, F. Lake, F. Rahm and C. Moberg, Mendeleev Commun. 2004, 14, 276; Y. Pei, K. Brade, E. Brulé, L. Hagberg, F. Lake and Moberg, C., Eur. J. Org. Chem. 2005, 2835.
The performance of P,N-ligands with pseudo-C2 and pseudo-Cs symmetry, the former “sterically C2-symmetric” but electronically asymmetric, the latter sterically meso but electronically asymmetric, in catalytic applications have led to valuable insight into the influence of electronic and steric properties in palladium catalyzed allylic alkylations: J.-L. Vasse, R. Stranne, R. Zalubovskis, C. Gayet and C. Moberg, J. Org. Chem. 2003, 68, 3258.
Self adaptable catalysts:
The discovery that ligands with pseudo-C2 symmetry result in higher selectivity for substrates giving rise to syn-syn-allyl complexes, whereas ligands with pseudo-Cs symmetry are preferred for reactions involving anti-anti-allyl complexes in Pd-catalyzed asymmetric alkylations led us to design and study a new type of catalysts capable of adapting their structure to the reacting substrate: R. Zalubovskis, E. Fjellander, Z. Szabó and C. Moberg, Eur. J. Org. Chem. 2007, 108; R. Zalubovskis, A. Bouet, E. Fjellander, S. Constant, D. Linder, J. Lacour, T. Privalov and C. Moberg, J. Am. Chem. Soc. 2008, 130, 1845.
We have contributed with the first enantioselective element-element addition to 1,3-dienes and the first example of allene formation via element-element addition to 1,3-enynes. Two surveys of the field have been published together with prof I Beletskaya: I. Beletskaya and C. Moberg, Chem. Rev. 1999, 99, 3435; I. Beletskaya and C. Moberg, Chem. Rev. 2006, 106, 2320; M. Gerdin and C. Moberg, Adv. Synth. Catal. 2005, 347, 749; M. Gerdin and C. Moberg, Org. Lett., 2006, 8, 2929; C. Lüken and C. Moberg, Org. Lett. 2008, ASAP.
We have developed several efficient methods for covalent attachment of ligands to solid supports, including the attachment of chiral ligands to planar and structured silicon surfaces. Several of the polymeric ligands have been shown to behave successfully in catalytic applications, allowing recovery and reuse of the chiral ligands up to 30 times and of the entire metal complex up to four times without loss in selectivity or reactivity: O. Belda, S. Lundgren and C. Moberg, Org. Lett. 2003, 5, 2275.M. Tilliet, S. Lundgren, C. Moberg and V. Levacher, Adv. Synth. Catal. 2007, 349, 364.
Micro reactors, high throughput screening: synthesis and analysis:
In order to enable efficient screening of reactions and reaction conditions we use micro reactors for the optimization of asymmetric metal catalyzed reactions. We have for example recently successfully studied the influence of the structure of Lewis bases in Lewis acid-Lewis base catalyzed additions of ketonitriles to aldehydes using microreactor technology. S. Lundgren, H. Ihre and C. Moberg, Archivoc, 2008, 6, 73.
Enzymatic determination of enantioselectivity and conversion in catalytic reactions:
We have developed an enzymatic method (jointly with prof K. Hult and coworkers) for the simultaneous analysis of yield and enantioselectivity in the synthesis of acylated cyanohydrins. The results have been published in A, Hamberg, S. Lundgren, M. Penhoat, C. Moberg and K. Hult, J. Am. Chem. Soc., 2006, 128, 2234; A. Hamberg, S. Lundgren, E. Wingstrand, C. Moberg and K. Hult, Chem Eur J, 2007, 13, 4334.