Diastereo- and Enantioselective Hydrogenative Aldol Coupling of Vinyl Ketones:  Design of Effective Monodentate TADDOL-Like Phosphonite Ligands

• Published in: Journal of the American Chemical Society 2008-03, Vol.130 (9), p.2746-2747
• Main Authors: Bee, Cisco, Han, Soo Bong, Hassan, Abbas, Iida, Hiroki, Krische, Michael J
• Format: Article
• Language: English
• Subjects: Catalysis; Crystallography, X-Ray; Dioxolanes - chemistry; Hydrogenation; Ketones - chemical synthesis; Ketones - chemistry; Ligands; Methanol - analogs & derivatives; Methanol - chemistry; Molecular Structure; Organometallic Compounds - chemistry; Organophosphorus Compounds - chemical synthesis; Organophosphorus Compounds - chemistry; Oxidation-Reduction; Rhodium - chemistry; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja710862u

We report the first enantioselective reductive aldol couplings of vinyl ketones, which were achieved through the design of a novel monodentate TADDOL-like phosphonite ligand. Specifically, hydrogenation of commercially available methyl vinyl ketone (MVK) or ethyl vinyl ketone (EVK) in the presence of aldehydes 1a−7a using cationic rhodium catalysts modified by chiral TADDOL-like phosphonite ligands AP-I and AP-IV produces aldol adducts 1b−7b and 1c−7c with excellent control of relative and absolute stereochemistry. The absolute stereochemical assignments of the aldol adducts are made in analogy to that determined for the 5-bromophthalimido derivative of aldol adduct 1b and the 2-bromo-5-nitrobenzoate of 3b, which were established by single-crystal X-ray diffraction analysis using the anomalous dispersion method.