Benjamin Schäffner

A General Palladium‐Catalyzed Amination of Aryl Halides with Ammonia

A new robust palladium/phosphine catalyst system for the selective monoarylation of ammonia with different aryl bromides and chlorides has been developed. The active catalyst is formed in situ from [Pd(OAc)(2)] and air- and moisture-stable phosphines as easy-to-handle pre-catalysts. The productivity of the catalyst system is comparable to that of competitive Pd/phosphine systems; full conversion is achieved with most substrates with 1-2 mol % of Pd source and a fourfold excess of ligand (L).

Iridium Phosphite−Oxazoline Catalysts for the Highly Enantioselective Hydrogenation of Terminal Alkenes

A modular library of readily available phosphite-oxazoline ligands (L1-L16a-f) has been successfully applied for the first time in the Ir-catalyzed asymmetric hydrogenation of a broad range of highly unfunctionalized 1,1,-disubstituted terminal alkenes. Enantioselectivities up to >99% and full conversions were obtained in several 1,1-disubstituted alkenes, including substrate classes that have never been asymmetrically hydrogenated before (i.e., 1,1-heteoraryl-alkyl, 1,1-diaryl, trifluoromethyl, etc.). The results indicated that these catalytic systems have high tolerance to the steric and electronic requirements of the substrate and also to the presence of a neighboring polar group. The asymmetric hydrogenations were also performed using propylene carbonate as solvent, which allowed the Ir catalyst to be reused and maintained the excellent enantioselectivities.

Enantioselective synthesis of tertiary α-hydroxyketones from unfunctionalized ketones: palladium-catalyzed asymmetric allylic alkylation of enolates.

Tertiary a-hydroxyketones are found in many biologically active compounds. These include the phytolexin lacineline C and the homoisoflavanone eucomol, both of which have a tetralone ring system. Despite their presence in a variety of biologically active targets, only a few catalytic methods are known to generate this functionality in an enantioselective fashion. Phase-transfer-catalyzed oxidations of simple ketones using molecular oxygen have been reported. However, in general, these methods require high catalyst loadings and only moderate enantioselectivities are obtained. Suzuki and co-workers developed an intramolecular crossed aldehyde–ketone benzoin cyclization with chiral triazolium salts as catalysts to access tertiary a-hydroxyketones in moderate to excellent yield and enantiomeric excess, but this strategy required high catalyst loadings (10–20 mol%). Sharpless and co-workers reported the osmium-catalyzed dihydroxylation of cyclic silyl enol ethers to give tertiary a-hydroxyketones. However, slight structural variation in the substrates resulted in large changes in the enantioselectivity using this method. Previously, we reported palladium-catalyzed decarboxylative asymmetric allylic alkylation (Pd-DAAA) of enolcarbonates to access both tertiary and quaternary stereocenters. To demonstrate the power of this transformation, we envisioned the oxidation of the enol carbonate, such that an additional oxygen functionality was present, for use as substrates in the Pd-DAAA to access highly oxygenated chiral products. We envisaged that simple, readily accessible allyl enol carbonates could be chemoselectively oxidized to yield the corresponding keto carbonates. Oxidation using m-CPBA should initially yield the corresponding epoxides, which could rearrange to give the more stable keto carbonates (Scheme 1). To our surprise, such an oxidation/rearrangement protocol was unprecedented in the literature. In a second step, these substrates could be enolized and protected to give the desired substrates for the Pd-DAAA reaction as shown in Scheme 2. As model substrates, tetralones and benzosuberones were chosen. The corresponding enol allyl carbonates were synthesized by selective O-acylation using allyl imidazole carboxylate along with boron trifluoride etherate, a high yielding method previously reported by our group (Table 1). Epoxidation of the enolcarbonates was achieved using m-CPBA in CH2Cl2 at room temperature (Scheme 3). For the encolcarbonates 2a–f, which are derived from tetralones, full conversion was observed after one hour. The reactions of the benzosuberone-derived substrates 2g and 2h were somewhat slower and the reaction was stopped after two hours at room temperature. The resulting epoxides are surprisingly stable even under aqueous conditions. The epoxide opening was facilitated by using BF3·OEt2 as the Lewis acid in Et2O. Under the described reaction conditions complete acyl migration was observed. Upon deprotonation of 4a–h with NaHMDS, the resulting enolates undergo complete acyl migration to form the thermodynamically favored regioisomer even at 78 8C. The enolate was then treated with MOMI, thus yielding the MOM-protected 1,2-endiol carbonate (Scheme 4). Similarly, the enolate could be treated with BOMI, thus affording the protected carbonate. Both the MOMand BOM-protected 1,2-endiol carbonates were obtained in good to excellent yield. The carbonates 5 a–l are stable and can be stored for Scheme 1. Synthesis of 1,2-endiol carbonates from simple enol carbonates. mCPBA= meta-chloroperbenzoic acid, PG = protecting group.