Andreas Hafner

Stereoselective transformations mediated by chiral monocyclo-pentadienyl titanium, zirconium, and hafnium complexes

The chiral cyclopentadienyldialkoxytitanium chlorides 3 and 4 with ligands deri- ved from (D)-glucose and tartaric acid afford highly stereoselective reagents for the addition of nucleophiles to aldehydes. The methyltitanium derivatives of 4 are unreactive, but interesting reagents result from mixtures of the chloride 4 and different organometallics before the trans- metalation occurs. Most successful for the methyl transfer are, however, the Cp*Zr- and Cp*Hf-analogs of the titanacycle 4. While the cyclic complex 4 is especially suited for the al- lyltitanation of aldehydes, the diacetoneglucose system 3 is the best choice for aldol reactions. The stereochemical course of these reactions can be rationalized by six-membered cyclic tran- sition states with either chair-conformation in the case of allyltitanations or boat-confoxmation for the aldolizations. Interactions of the alkoxy ligand(s) with the cyclopentadienyl group seem to be crucial for good stereoselectivity. The mechanism of the often perfect enantiofacial diffe- rentiations is, however, still unclear and might be due to stereoelectronic effects. These rea- gents have been successfully applied for the synthesis of C(2)-modified pentoses from glycer- aldehyde.

A two-step continuous-flow procedure towards ribociclib

This work describes the manufacturing of ribociclib following the concept of an end-to-end continuous-flow process. The active pharmaceutical ingredient (API) is produced in a two-step telescoped flow process with integrated in-line liquid-liquid extraction and semibatch crystallization.

53Cr Nuclear Magnetic Resonance Studies of Pentacarbonylchromium Carbene Complexes

The 53Cr nmr spectra of forty six chromium carbene complexes were recorded, and the chemical shift and line width data were discussed, along with associated infrared, UV-visible, and 13C spectroscopic data1. The 53Cr chemical shifts correlated very well with the donor-acceptor properties of the carbene ligand, and were quite sensitive to steric influences on efficiency of π-overlap of the heteroatom with the carbene carbon. No correlation was observed between the 53Cr chemical shift and the reactivity with imines to form β-lactams; however, the line width appeared to be related to reactivity. Preliminary attempts to utilize 53Cr nmr data to direct the synthetic utilization of chromium carbene complexes are reported.