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Don't hold on too tightly! In a new dirhodium catalyst for C-H functionalization reactions, two tropolonato ligands are introduced as hemilabile chelating ligands (see scheme). Only two bridges hold the Rh-Rh core together. The tropolonato ligands can liberate a binding site in the equatorial coordination sphere of the catalyst. This opens a doorway to new mechanistic channels in C-H functionalization., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The regio- and enantioselective alpha-allylation of unstabilized ketone enolates with unsymmetrical allylic carbonates to form the branched substitution products in the presence of metallacyclic iridium catalysts is reported. The products, branched gamma,delta-unsaturated ketones, were obtained from readily available silyl enol ethers and achiral Boc-protected allylic alcohols in high regioselectivities and enantioselectivities (91-96% ee). The combination of CsF and ZnF2 was shown to promote this reaction and suppress the formation of diallylation byproducts. In addition, iridium complexes derived from simple phosphoramidite ligands were shown to catalyze this reaction with excellent selectivities, and spectroscopic data show that a cyclometalated Ir precatalyst is formed in situ. This process provides an enantioselective access to synthetically important bifunctional compounds, which are generally accessible, but in racemic form, through Claisen rearrangements. Ten examples of the reactions of aromatic, as well as aliphatic, substrates are reported.

[reaction: see text] A synthesis of the antimitotic alkaloids (-)-colchicine and (-)-isocolchicine is reported. Important steps are (a) enantioselective transfer-hydrogenation of an alkynone, (b) iodine/magnesium exchange with subsequent aromatic acylation, (c) Rh-catalyzed transformation of an alpha-diazoketone into an oxatetracyclic key intermediate through intramolecular [3 + 2]-cycloaddition of an in situ generated carbonyl ylide, and (d) regioselective conversion of the cycloadduct into a tropolone derivative. The new synthetic strategy opens an efficient enantioselective access to colchicine and structural analogues.

Colchicine, the major alkaloid of the meadow saffron, is one of the most prominent natural products and, like other tubulin-binding natural products (e.g. taxol and the epothilones), exhibits great pharmaceutical potential. The first syntheses in the late 1950s were milestones in natural product synthesis. But even today this structurally supposedly simple molecule poses a challenge to synthetic chemists. Only in the last years have syntheses been developed that are efficient enough to provide novel structurally modified colchicine analogues. The comparative examination of all known colchicine total syntheses undertaken in this Review not only reveals the tremendous progress in synthetic organic methodology over the past decades, but also shows how the unique synthetic problems posed by this molecule can be solved in an exceptionally creative manner. Only a few target molecules have been synthesized in such multifaceted ways.