Synthesis of α-aryl carbonyl compounds is important because an array of natural products and pharmaceutically relevant molecules contain this moiety.1 The introduction of aryl groups at the α-position of carbonyl compounds was initially addressed in the Pd-catalyzed cross-coupling of enolate species with aryl halides.2 However, strong base involved limited their applications in the synthesis of tertiary α-arylated carbonyl compounds, due to a facile racemization of the product.3
A potential solution to this synthetic problem has recently emerged, employing Brønsted acid-catalyzed oxygenative arylation of ynamides.4 These processes occur under mildly acidic conditions, and thus the racemization can be kept to a minimum. We introduce an external oxidant. Herein, we report a reagent-controlled enantioselective oxidation reaction, using a chiral N,N’-dioxide. In this external oxidant approach, unmodified nucleophilic arenes could be employed and the product is now free of trace groups from the oxidant, thereby avoiding two unnecessary steps. Furthermore, the byproduct of the oxidation (mono-N-oxide) could be recycled at the end in an efficient manner. Various nucleophilic arenes, including indoles, phenols, and pyrroles, participate in the oxygenative alkylation, and enantioselectivity upto 92%ee was realized.
1. Bellina, F.; Rossi, R. Chem. Rev. 2010, 110, 1082-1146. (b) Johansson, C. C. C.; Colacot, T. J. Angew. Chem. Int. Ed. 2010, 49, 676-707.
2. Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 12382-12383.
3. Chae, J.; Yun, J.; Buchwald, S. L. Org. Lett. 2004, 6, 4809-4812.
4. (a) Kaldre, D.; Maryasin, B.; Kaiser, D.; Gajsek, O.; González, L.; Maulide, N., Angew. Chem. Int. Ed. 2017, 56, 2212-2215. (b) Kaldre, D.; Maulide, N. Science, 2018, 361, 664-667.