2-Aminobenzaldehydes as Versatile Substrates for Rhodium-Catalyzed Alkyne Hydroacylation: Application to Dihydroquinolone Synthesis**

Alkene and alkyne hydroacylation reactions are archetypal examples of simple addition processes that display excellent atom economy. Both reactions result in the formation of a new C C bond and deliver synthetically useful carbonylcontaining products. In recent years, there has been considerable interest in converting these processes into synthetically useful transformations. Transition-metal-catalyzed variants represent the largest class of hydroacylation reactions, and amongst these, processes that involve some form of chelation control dominate. The need to employ a chelating substrate stems from the fact that the majority of the metal-catalyzed examples proceed through an inherently unstable acyl metal intermediate 1 (Scheme 1), which can lead to the formation of unwanted side products formed by decarbonylation. A limitation of the chelation-controlled strategy is that the coordinating group, which is present to stabilize the metal– acyl intermediate 2, will also be present in the product. If this group is not needed in the final product, then it must be removed or converted into an alternative functional group. Despite this limitation, the advantages of this chelationcontrolled process, such as mild reaction conditions, control of enantioand regioselectivity, and broad substrate scope, have resulted in widespread applications of this approach. One strategy to overcome the innate limitation of a chelationcontrolled approach is to develop catalytic methods that function without the need for such coordinating groups; although there are notable examples of success with this approach, significant limitations with regard to substrate scope and enantioand regioselectivity remain. An alternative strategy is to consider the need for a chelating unit as an opportunity, and to expand the range of effective coordinating groups, so that a large variety of useful functional groups can act as the crucial chelating motif. As synthetic chemistry is generally concerned with the preparation of functionalized molecules, an approach that is tolerant of, or indeed benefits from, as many useful functional groups as possible should find wide application. Herein, we demonstrate that simple and readily available 2-aminobenzaldehydes are excellent substrates for intermolecular Rh-catalyzed alkyne hydroacylation, and in doing so add to the motifs available for use in these valuable processes. Furthermore, the products of these reactions, amino-substituted enones, were directly converted into a series of useful dihydroquinolone heterocycles. The first intermolecular metal-catalyzed alkene hydroacylation, which employed an aldehyde with a coordinating C=C bond, was reported by Lochow and Miller. Since this initial report, the most popular substrates for chelationcontrolled reactions feature heteroatom coordination, and systems that include oxygen (3), sulfur (4, 5), and, to a more limited extent, phosphorus substituents have all been reported. Although there are also some precedents for the use of nitrogen-based functional groups, examples are scarce and mostly either poor yielding or limited to very specific substrates. Suggs first reported the use of nitrogen chelation when he employed quinoline-8-carboxyaldehyde (6) as a substrate in the presence of a stoichiometric amount of Wilkinson s complex. Picolyl imines 7 were first used as removable or catalytic chelating groups by Suggs; significant advances were then achieved by Jun et al. and other groups. However, these reactions require harsh reaction Scheme 1. Chelation-free (a) and chelation-controlled intermolecular alkyne hydroacylation (b). The most common chelating aldehyde motifs are also shown (3–7), along with the 2-aminobenzaldehyde framework 8 and examples demonstrating the ubiquity of the 2-aminocarbonyl unit in biologically significant heterocycles.