Markus Granitzka

A Facile Route to Functionalized N-Heterocyclic Carbenes (NHCs) with NHC Base-Stabilized Dichlorosilylene

Reaction of IPr x SiCl(2) (1) [IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] with 1-azidoadamantane leads to functionalized N-heterocyclic carbene (NHC) 2. Silyl-substituted NHC 2 reacts easily with 1-azidoadamantane to form triazene 3, in which the exocyclic C=N bond is slightly shorter than those of regular NHC-derived triazines. 2 could serve as a promising ligand for transition metals.

Stable silaimines with three- and four-coordinate silicon atoms.

The reactions of silylenes with organic azides are quite diverse, depending on the substituents of the silylene center and on the nature of the azide employed. Elusive silaimine with three-coordinate silicon atom L(1)SiN(2,6-Triip(2)-C(6)H(3)) (5) {L(1) = CH[(C═CH(2))(CMe)(2,6-iPr(2)C(6)H(3)N)(2)] and Triip = 2,4,6-triisopropylphenyl} was synthesized by treatment of the silylene L(1)Si (1) with a sterically demanding 2,6-bis(2,4,6-triisopropylphenyl)phenyl azide (2,6-Triip(2)C(6)H(3)N(3)). The reaction of Lewis base-stabilized dichlorosilylene L(2)SiCl(2) (2) {L(2) = 1,3-bis(2,6-iPr(2)C(6)H(3))imidazol-2-ylidene} with Ph(3)SiN(3) afforded four-coordinate silaimine L(2)(Cl(2))SiNSiPh(3) (6). Treatment of 2,6-Triip(2)C(6)H(3)N(3) with L(3)SiCl (3) (L(3) = PhC(NtBu)(2)) yielded silaimine L(3)(Cl)SiN(2,6-Triip(2)-C(6)H(3)) (7) possessing a four-coordinate silicon atom. The reactions of L(3)SiN(SiMe(3))(2) (4) with adamantyl and trimethylsilyl azide furnished silaimine compounds with a four-coordinate silicon atom L(3)(N(Ad)SiMe(3))SiN(SiMe(3)) (8) (Ad = adamantyl) and L(3)(N(SiMe(3))(2))SiN(SiMe(3)) (9). Compound 8 was formed by migration of one of the SiMe(3) groups. Compounds 5-9 are stable under inert atmosphere and were characterized by elemental analysis, NMR spectroscopy, and single-crystal X-ray studies.

Characterization of a Multicomponent Lithium Lithiate from a Combined X-Ray Diffraction, NMR Spectroscopy, and Computational Approach

An unusual lithium lithiate [Li(diglyme)2][(diglyme)Li2(C4H3S)3], made up from three carbanions, two lithium cations, and a single donor base molecule in the anion and a single lithium cation, coordinated by two donor base molecules, is investigated in a combined study including X-ray diffraction, NMR spectroscopy and computational approaches in solution and the solid state. While the multicomponent lithiate is the only species present in the solid state, solution NMR spectroscopy and computational methods were employed to identify a second species in solution. The dimer [(diglyme)Li(C4H3S)]2 coexists with the lithiate in solution in a 1:1 ratio, the more the higher the polarity of the solvent is. Only the combination of this multitude of methods provides a firm picture of the whole.

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

Summary (2S,3S)-3-Hydroxyleucine can be found in an increasing number of bioactive natural products. Within the context of our work regarding the total synthesis of muraymycin nucleoside antibiotics, we have developed a synthetic approach towards (2S,3S)-3-hydroxyleucine building blocks. Application of different protecting group patterns led to building blocks suitable for C- or N-terminal derivatization as well as for solid-phase peptide synthesis. With respect to according motifs occurring in natural products, we have converted these building blocks into 3-O-acylated structures. Utilizing an esterification and cross-metathesis protocol, (2S,3S)-3-hydroxyleucine derivatives were synthesized, thus opening up an excellent approach for the synthesis of bioactive natural products and derivatives thereof for structure activity relationship (SAR) studies.

A biomimetic domino reaction for the concise synthesis of capreomycidine and epicapreomycidine

The non-proteinogenic amino acids capreomycidine and epicapreomycidine are constituents of antibiotically active natural products, but the synthesis of these unusual cyclic guanidine derivatives is challenging. The biosynthesis of capreomycidine has therefore been employed as a guideline to develop a concise biomimetic synthesis of both epimeric amino acids. The resulting domino-guanidinylation-aza-Michael-addition reaction provides the most convenient access to these amino acids in racemic form. Attempts to dissect the domino reaction into two separate transformations for a stereocontrolled version of this synthetic approach have also been made. The synthesized didehydro-arginine derivatives with urethane-protected guanidine moieties did not undergo the aza-Michael-addition anymore. These results may have wider implications for the 1,4-addition of guanidines to α,β-unsaturated carbonyl compounds, particularly to didehydro amino acids.

Concise Synthesis and X-Ray Crystal Structure of N-Benzyl-2-(pyrimidin-4′-ylamino)-thiazole-4-carboxamide (Thiazovivin), a Small-Molecule Tool for Stem Cell Research

Abstract Stem cell research is one of the most promising fields of modern biomedical research and regenerative medicine. Limited availability and ethical concerns suggest the renouncement of embryonic stem cells (ESCs), thus raising the need for more efficient procedures for the generation of stem cells, ideally through reprogramming of mammalian cells. The small molecule N-benzyl-2-(pyrimidin-4′-ylamino)-thiazole-4-carboxamide (thiazovivin) is known to improve the generation of human induced pluripotent stem cells (iPSCs) from human fibroblasts. We herein describe a highly efficient procedure for the synthesis of thiazovivin over just five steps, which should be suitable for a large-scale application, and the first x-ray crystal structure of the target compound. [Supplementary materials are available for this article. Go to the publishers online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.] GRAPHICAL ABSTRACT

Polymorphism of Dibromo-tetrakis(tetrahydrofuran-κO)magnesium(II)

The title compound, [MgBr2(C4H8O)4] (1a), forms twinned four-component monoclinic crystals as a new polymorph, space group P21/n with Z´ = 2, in addition to the already known tetragonal polymorph (1b). Although the molecular parameters in the two polymorphs match very well, the packing patterns are significantly different. Furthermore, the correct constitution of the mixed halide bromo-chloro-tetrakis(tetrahydrofuran-κO)magnesium(II) (2) could be determined. Graphical Abstract Polymorphism of Dibromo-tetrakis(tetrahydrofuran-κO)magnesium(II)

Bis-2-thienyldiethylaminophosphane as a Ligand in Late Transition Metal Complexes and its Transformation to Bis-2-thienylphosphane

Abstract Bis-2-thienyldiethylaminophosphane (C4H3S)2PNEt2 (1) is introduced as a ligand for late transition metal complexes ([(H3C4S)2PNEt2]nMXmLp), with M = Ni(II), Au(I), Cu(I), Pd(II), Ir(I), X = Cl, Br and L = NCMe, COD, (2-7). Reactions of 1 with the late transition metal salts NiCl2·dme, (Me2S)AuCl, CuCl, PdCl2(PhCN)2, and [Ir(COD)Cl]2 yield the complexes [{(H3C4S)2PNEt2}2 · NiCl2] (2), [(H3C4S)2PNEt2 · AuCl] (3) [(H3C4S)2PNEt2·CuCl(CH3CN)]2 (4), [{(H3C4S)2PNEt2}2 · PdCl2] (5), [{(H3C4S)2PNEt2}2·PdCl2]2 (6), and [(H3C4S)2PNEt2·IrCl(COD)] (7). In addition, the transformation of 1 to the valuable chlorine-substituted starting material (H3C4S)2PCl (8) and the related conversion of 8 to the secondary phosphane (H3C4S)2PH (9) is reported. The complexes 2-7 are stable under inert gas conditions and were characterized by single-crystal X-ray studies, NMR spectroscopy, and elemental analysis.