Biomedical subjects
Publications and source records attributed to Carsten Bolm.
[reaction: see text] A simple and mild copper salt-catalyzed N-arylation of sulfoximines in high yields is reported. Cu(OAc)(2) activates aryl boronic acids for the reaction with NH-sulfoximines without additional base or heating. Furthermore, this new method allows the preparation of N-arylated sulfoximines, which have previously been more difficult to access.
[reaction: see text] Palladium-catalyzed alpha-arylation of N-benzoyl sulfoximine ethyl ester with various aryl bromides leads to alpha-arylated products that can easily be hydrolyzed, giving the corresponding N-protected benzyl phenyl sulfoximines. In this manner, new sulfoximine derivatives are accessible that have so far been difficult to prepare in enantiopure form.
[reaction: see text] Various ferrocene-based organosilanols have been synthesized in four steps starting from achiral ferrocene carboxylic acid. Applying these novel planar-chiral ferrocenes as catalysts in asymmetric phenyl transfer reactions to substituted benzaldehydes afforded products with high enantiomeric excesses. The best result (91% ee) was achieved in the addition to p-chlorobenzaldehyde with organosilanol 2b, which has a tert-butyl substituent on the oxazoline ring and an isopropyl group on the silanol fragment.
[reaction: see text] The asymmetric synthesis and chemical modification of p-bromophenyl methyl sulfoximine (2) is described. Starting from p-bromophenyl menthyl sulfinate (5), enantiopure 2 can be obtained in a short reaction sequence involving a well-established substitution reaction followed by stereospecific imination with O-mesitylenesulfonylhydroxylamine (MSH). Palladium-catalyzed Buchwald/Hartwig, Suzuki, and Stille coupling reactions allow a broad variation of the sulfoximine aryl group, which is otherwise difficult to achieve. The incorporation of a p-morpholino-substituted derivative into a pseudotripeptide demonstrates the applicability of the novel sulfoximine derivatives.
Explore the source record for details and available documents.
The addition of Ph(2)Zn to aldehydes has been investigated by DFT calculations. The experimentally observed increase in enantioselectivity upon addition of Et(2)Zn to the reaction mixture is rationalized from calculations of all isomeric transition states. Spectator ethyl groups in the transition state do not lower the intrinsic activation barrier, but instead increase it. In the presence of a bulky ligand, the inherently preferred all-phenyl transition state is selectively disfavored. The paths with less sterically demanding spectator ethyl groups will experience a more drastic ligand acceleration, and thus the influence of the ligand would be expected to be stronger in the presence of Et(2)Zn, in agreement with experimental observations.
The development of an enantioselective sulfide oxidation involving a chiral iron catalyst and aqueous hydrogen peroxide as oxidant is described. In the presence of a simple carboxylic acid, or a carboxylate salt, the reaction affords sulfoxides with remarkable enantioselectivities (up to 96 % ee) in moderate to good yields. The influence of the structure of the additive on the reaction outcome is reported. In the sulfoxide-to-sulfone oxidation a kinetic resolution (with s = 4.8) occurs, which, however, plays only a negligible role in the overall enantioselective process. Furthermore, a positive nonlinear relationship between the ee of the product and that of the catalyst has been found. On the basis of these observations, a possible catalyst structure is proposed.
A chiral pyrrolidinylmethanol derivative containing perfluoro-ponytails (5) was prepared from (S)-proline. The use of this perfluoro-substituted amino alcohol in catalytic asymmetric additions of organozinc reagents to aldehydes affords products with high enantioselectivities in both pure hexane and a mixture of hexane and FC-72 (perfluorohexane). Enantiomeric excesses up to 94 and 88 % ee have been achieved in Et(2)Zn and Ph(2)Zn additions, respectively. For the reactions in the biphasic solvent system a striking temperature effect was observed. Thus, when the temperature was raised from 0 to 40 degrees C the ee value of the product increased from 81 to 92 %. Furthermore, the catalyst loading could be remarkably low, and with only 0.1 mol % of amino alcohol 5 a product with 90 % ee was obtained in the Et(2)Zn addition to benzaldehyde in hexane. The perfluoro-ligand was easily recovered by simple phase separation, and until the ninth repetition its reuse proceeded without significant loss of enantioselectivity and reactivity.
For several decades, enamines and related compounds have been used as intermediates in organic synthesis and many methods are known for their preparation. Most of the synthetic protocols, however, require harsh reaction conditions. Recently, a new approach has emerged, inspired by the analogous arylation of amines catalysed by palladium or copper complexes (Buchwald-Hartwig reaction). Simultaneous and independent work from several research groups has led to the development of very powerful protocols for the preparation of enamines and their derivatives that require only readily available starting materials and proceed under very mild reaction conditions. Noteworthy is the fact that in less than five years an almost unknown reaction has reached such a high level of scope and generality that it is now very frequently applied in total syntheses of natural products.
New previously unavailable N-vinyl sulfoximines have been synthesized by intermolecular palladium-catalyzed coupling between sulfoximines and vinyl bromides in excellent yield. Hydrogenation of the vinyl moiety opens a novel way to alpha-branched N-alkyl sulfoximines.
Explore the source record for details and available documents.
[reaction: see text] Copper-mediated cross-coupling reactions of sulfoximines with aryl iodides and aryl bromides provide N-arylated sulfoximines in high yields. The method is complementary to the known palladium-catalyzed N-arylation and allows the preparation of N-arylated sulfoximines, which have previously been inaccessible.
Explore the source record for details and available documents.
N-Acylated sulfoximines display unique chemical properties. Various derivatives have been synthesized and investigated by NMR and IR spectroscopy. The results of these studies suggest that the bond between the sulfoximine nitrogen atom and the carbonyl group has a less pronounced double-bond character than the corresponding bond in an amide. This assumption is supported by the first X-ray crystal structure of a sulfoximidoyl derivative. Ab initio calculations (MP2/6-311++G**) provide further insight into the electronic nature of the N-acyl fragment. Studies of the chemical behavior of N-acylated sulfoximines indicate the presence of a highly electrophilic carbonyl group. Thus, the N--C(O) bond can easily be cleaved under mild basic conditions, and the acidity of the hydrogen atoms alpha to the sulfoximine carbonyl group is high. As a consequence of the latter property, endo,endo-sulfoximidoyl norbornene derivatives readily isomerize to their endo,exo counterparts, and sulfoximine-containing pseudopeptides can easily epimerize at the stereogenic center next to the N--C(O) carbonyl group.
Small amounts of simple methoxy poly(ethylene glycol)s (MPEGs) have a beneficial effect on catalyzed asymmetric aryl and alkyl transfer reactions onto aldehydes. The enantiomeric excesses of the products are improved, and this "MPEG effect" allows a reduction of the catalyst loading by a factor of 10.
The Rh(II)-catalyzed imination of sulfoxides and sulfides using [Rh(2)(OAc)(4)] as a catalyst and trifluoroacetamide or sulfonylamides in combination with iodobenzene diacetate and magnesium oxide affords sulfoximines and sulfilimines, respectively, in a stereospecific manner. [reaction: see text]
Starting from readily accessible endo-cis-(2S,3R)-norbornene dicarboxylic acid benzyl monoester, a general and efficient synthetic approach toward unsymmetrical two-stranded peptidic structures was developed. In these structures the peptide strands are oriented in a parallel geometry. Their synthesis is easily applicable to a variety of amino acids and peptides. Specifically, a norbornane template as molecular scaffold induces hydrogen bonding between the adjacent peptide strands. The specific hydrogen bonding patterns between these strands were revealed by detailed NMR analysis including TOCSY/NOE experiments.
Explore the source record for details and available documents.