Enantioselective hydrogenation of furans and benzofurans remains a challenging task. We report the hydrogenation of 2- and 3-substituted furans by using iridium catalysts that bear bicyclic pyridine-phosphinite ligands. Excellent enantioselectivities and high conversions were obtained for monosubstituted furans with a 3-alkyl or 3-aryl group. Furans substituted at the 2-position and 2,4-disubstituted furans proved to be more difficult substrates. The best results (80-97% conversion, 65-82% enantiomeric excess) were obtained with monosubstituted 2-alkylfurans and 2-[4-(trifluoromethyl)phenyl]furan. Benzofurans with an alkyl substituent at the 2- or 3-position also gave high conversions and enantioselectivity, whereas 2-aryl derivatives showed essentially no reactivity. The asymmetric hydrogenation of a 3-methylbenzofuran derivative was used as a key step in the formal total synthesis of the cytotoxic naphthoquinone natural product (-)-thespesone.

SummaryA synthesis of new NeoPHOX ligands derived from serine or threonine has been developed. The central intermediate is a NeoPHOX derivative bearing a methoxycarbonyl group at the stereogenic center next to the oxazoline N atom. The addition of methylmagnesium chloride leads to a tertiary alcohol, which can be acylated or silylated to produce NeoPHOX ligands with different sterical demand. The new NeoPHOX ligands were tested in the iridium-catalyzed asymmetric hydrogenation and palladium-catalyzed allylic substitution. In both reactions high enantioselectivities were achieved, that were comparable to the enantioselectivities obtained with the up to now best NeoPHOX ligand derived from expensive tert-leucine.

Invited for the cover of this issue is the group of Andreas Pfaltz at the University of Basel. The image depicts the catalytic reaction used as a key step in the synthesis of thespesone, embellished with a drawing of the plant from which this natural product was isolated. Read the full text of the article at .

Excellent enantioselectivities and high conversions are achieved for 3‐substituted furans (I) and 2‐substituted benzofurans (VII).

Enantioselective hydrogenation of furans and benzofurans remains a challenging task. In their Full paper on A. Pfaltz et al. report the hydrogenation of differently substituted furans and benzofurans by using iridium catalysts bearing bicyclic pyridine–phosphinite ligands. Excellent enantioselectivities and high conversions were obtained in this transformation. The asymmetric hydrogenation of a 3‐methylbenzofuran derivative was used as a key step in the formal total synthesis of the cytotoxic naphtoquinone natural product (−)‐thespesone.