Total Synthesis of Lamellarins U and A3 by Interrupting Halogen Dance

A total synthesis of lamellarins U and A3 is described. The synthesis features interruption of a halogen dance reaction of a metalated α,β-dibromopyrrole. The pyrrolylmagnesium reagent, generated by deprotonative metalation using (TMP)MgCl·LiCl (TMP: 2,2,6,6-tetramethylpiperidide) as base, was transmetalated to the corresponding organozinc species without causing the halogen dance reaction, which underwent a Negishi coupling to incorporate an aryl group onto the pyrrole ring. The arylated α,β-dibromopyrrole was then converted into lamellarins U and A3 through an α-selective halogen–magnesium exchange followed by carboxylation and subsequent palladium-mediated cyclization. The late-stage introduction of another aryl group was performed using a Kosugi–Migita–Stille coupling to provide lamellarins U and A3.

1,2,3-Tri(9-anthryl)benzene. Photophysical Properties and Solid State Intermolecular Interactions of Radially Arranged, Congested Aromatic π-Planes

We report the Negishi coupling based synthesis of 1,2,3-tri(9-anthryl)benzene derivatives, containing three radially arranged anthracenes in a π-cluster. In the crystalline state of the unsubstituted derivative, intermolecular π-π and CH-π interactions between the anthracene units drive the formation of a two-dimensional packing structure. Owing to though-space π-conjugation between anthracene units, the substances have unique electronic properties. The excited state dynamic behavior occurring between the three radially arranged anthracene moieties, such as exciton localization/delocalization, was elucidated by means of transient absorption measurements and quantum chemical calculations. Interestingly, even though the three anthracenes are closely oriented with a ca. 3.0 Å distances between their C-9 positions, exciton localization on two anthracene units is energetically favorable because of the flexible nature of the radially arranged aromatic rings.

Synthesizing highly fluorinated oligophenyls via Negishi coupling of fluoroarylzinc pivalates

Previously established general synthetic methods for the synthesis of highly fluorinated biphenyls using Suzuki-Miyaura protocols require the use of organoboron compounds which are not very stable under reactions conditions and thus need to be used in large excess. Herein we report an improved general strategy for the synthesis of highly fluorinated biphenyls, terphenyls and phenyl-substituted terphenyls using organozinc pivalates. The influence of several parameters was investigated: a) in a series of different monodentate phosphine ligands, X-Phos showed the best performance; b) a higher yield could be obtained for substrates bearing less steric hindrance or lower amount of fluorine substitution; c) as iodinated substrates decomposed during the reaction, brominated electrophiles were found to be superior. The presented protocol is scalable, versatile, and works with commonly used and commercially available phosphine ligands (X Phos) and palladium sources (Pd2dba3). Also, it does not need excess nucleophile usage for terphenyl synthesis and only a slight such excess for the preparation of phenyl substituted terphenyls.

Practical Synthesis of Iboxamycin, a Potent Antibiotic Candidate, in Amounts Suitable for Studies in Animal Infection Models

A gram-scale synthesis of iboxamycin, an antibiotic candidate bearing a fused bicyclic amino acid residue, is presented. A pivotal transformation in the route involves an intramolecular hydrosilylation–oxidation sequence to set the ring-fusion stereocenters of the bicyclic scaffold. Other notable features of the synthesis include a high-yielding, highly diastereoselective alkylation of a pseudoephenamine amide, a convergent sp³–sp² Negishi coupling, and a one-pot transacetalization–reduction reaction to form the target compound’s oxepane ring. Implementation of this synthetic strategy has provided ample quantities of iboxamycin to allow for its <i>in vivo</i> profiling in murine models of infection.

Practical Synthesis of Iboxamycin, a Potent Antibiotic Candidate, in Amounts Suitable for Studies in Animal Infection Models

A gram-scale synthesis of iboxamycin, an antibiotic candidate bearing a fused bicyclic amino acid residue, is presented. A pivotal transformation in the route involves an intramolecular hydrosilylation–oxidation sequence to set the ring-fusion stereocenters of the bicyclic scaffold. Other notable features of the synthesis include a high-yielding, highly diastereoselective alkylation of a pseudoephenamine amide, a convergent sp³–sp² Negishi coupling, and a one-pot transacetalization–reduction reaction to form the target compound’s oxepane ring. Implementation of this synthetic strategy has provided ample quantities of iboxamycin to allow for its <i>in vivo</i> profiling in murine models of infection.

Homogeneous Catalyzed Aryl–Aryl Cross-Couplings in Flow

Aryl–aryl cross-coupling reactions are important reactions for the production of various biaryl compounds. This short review covers the various aryl–aryl cross-coupling reactions carried out in flow, focusing on the metal species of the aryl nucleophiles used in the cross-coupling reactions.1 Introduction2 Suzuki–Miyaura Coupling (B)3 Migita–Kosugi–Stille Coupling (Sn)4 Negishi Coupling (Zn)5 Kumada–Tamao–Corriu Coupling (Mg)6 Murahashi Coupling (Li)7 Conclusion