The tandem asymmetric conjugate addition of alkyl or aryl groups to enones and subsequent silyl trapping has already been achieved and yields valuable silyl enol ethers. Herein, the first method for the respective addition of alkenyl groups is reported, which is based on a rhodium(I)‐catalyzed addition of readily available alkenylzirconocenes. As prerequisite for silyl trapping, the initially formed enolates have to be transmetalated from zirconium to lithium by treatment with methyllithium prior to addition of the silyl chloride. Starting from 5‐ to 7‐membered cycloalkenones, the respective silyl enol ethers were obtained in excellent yields and ≥93% ee; an acyclic substrate furnished a moderate enantioselectivity. Besides trimethylsilyl chloride, the silylation was also performed with tert‐butyldimethylsilyl chloride, and the synthetic scope was evaluated by employing five different alkenyl groups. Moreover, the mechanism of this sequence was elucidated by 1H NMR studies, and the efficiency of catalyst control was exemplified by synthesis of a cis‐3,5‐disubstituted cyclohexanone which, due to strong substrate control, cannot be obtained by copper‐catalyzed conjugate addition.magnified image

Rhodium(I)/Binap complexes catalyze highly enantioselective additions of methyl- and arylaluminum reagents to cyclic α,β-unsaturated N-tosyl ketimines. Depending on the solvent and substituents at the ring, the reaction occurs either in a 1,2-manner to deliver α-tertiary allylic amines or in a 1,4-manner to yield, after subsequent reduction, 3-substituted cycloalkyl amines. Well known in the case of the respective cycloalkenones, these first transformations of the aza-analogues enable the synthesis of amine structures of pharmaceutical and biochemical interest.

(R)-Sarkomycin was prepared using a five-step total synthesis. Key steps in the enantioselective construction of the targeted scaffold were a rhodium-catalyzed asymmetric conjugate alkenyl addition with subsequent silyl trapping and a Mukaiyama aldol reaction with aqueous formaldehyde. Protection of the hydroxy group as a THP acetal and oxidative cleavage of the C,C-double bond provided a stable direct precursor to the natural product. The final liberation was carried out under slightly acidic conditions in a microwave-assisted reaction, resulting in a high yield of the "deceptive" sarkomycin. This represents the shortest enantioselective synthesis of this rather unstable compound to date and the first to employ asymmetric catalysis to introduce the stereogenic center.

Keywords: Bafilomycin / Concanamycin / Fluorous chromatography / Perfluorinated reagents / Photoaffinity labeling / VATPase inhibitors (Trifluoromethyl)diazirines are well established photoaffinity labels (PAL) used in biochemical investigations to create covalent ligand-receptor bonds. Two new diazirinylbenzoic acids 8b,c with perfluorobutyl and perfluorooctyl chains (F-PAL) were efficiently prepared from p-bromobenzaldehyde and attached to the highly potent and specific V-ATPase inhibitors 21-deoxyconcanolide A (2) and bafilomycin A 1 (5), deriving from the natural product pool from Streptomyces producer strains. The labelled derivatives 17 and 18 were efficiently purified by fluorous solid-phase extraction. Func-

N‐Sulfonylimines of cycloalk‐2‐enones are well‐suited for the enantioselective rhodium(I)/binap‐catalyzed 1,4‐additions of arylzinc halides. The cyclic enamides, obtained after quenching, are sensitive towards chromatography, but can undergo diastereoselective reductions to furnish cis‐ or trans‐3‐arylcycloalkylamines with five‐ to seven‐membered rings. The 1,4‐addition is not influenced by a methyl group at C‐5 of six‐membered rings, providing further configurational options. 3‐Arylcycloalkylamines are subunits in a number of bioactive substances and can also be oxidatively transformed into cyclic γ‐amino acids.magnified image