Gold-catalyzed intermolecular oxidations of internal alkynes have been achieved with high regioselectivities using 8-alkylqinoline N-oxides as oxidants and in the absence of acid additives. Synthetically versatile α,β-unsaturated carbonyls are obtained in good to excellent yields and with excellent E-selectivities. A range of functional groups such as THP, MOMO, N 3 , OTBS, and NBoc are tolerated. This reaction allows to mask α,β-unsaturated carbonyls as propargyl moieties, thus offering a practical solution to issues of functional group compatibility with α,β-unsaturated carbonyls, likely encountered in syntheses of complex structures.Although alkene epoxidation is a classic and versatile reaction in organic synthesis, epoxidation of C-C triple bonds1 with DMDO or peracids has little synthetic utility except with electronically biased ynamide substrates2 as often multiple products including α,β-unsaturated ketones were formed with little chemoselectivity and regioselectivity. Many of the product formations could be rationalized via an initial rearrangement of oxirene A3 into highly reactive α-oxocarbene B (Scheme 1A). In the cases of alternative metal-mediated/ catalyzed intermolecular alkynes oxidation, further oxidation is unavoidable,4 leading to α,β-epoxy ketones,5 1,2-dicarbonyl, or carboxylic products;6 hence, regioselectivity has not been studied nor achieved. Herein, we report a rare highly regioselective single oxidation of internal alkynes via gold catalysis under exceedingly mild conditions, and synthetically versatile α,β-unsaturated carbonyls are directly formed from propargyl moieties for the first time in good yields and with high to excellent regioselectivities.We have recently reported that terminal alkynes or alkynoates can be oxidized intermolecularly into α-oxo gold carbene C,7 which could be trapped efficiently by tethered OH groups.8 We envisioned such a gold carbene intermediate, if generated from internal alkynes, might undergo facile 1,2-C-H insertions, thus avoiding further oxidation and forming highly valuable α,β-unsaturated carbonyls (Scheme 1B). This gold catalysis would make a propargyl moiety a masked α,β-unsaturated carbonyl;9 however, the challenge is how to achieve high regioselectivities10 without much structural bias in the substrate.To our delight, the oxidation of symmetric 6-dodecyne indeed afforded α,β-unsaturated ketone 2a in 77% yield albeit sluggish reaction (Eq. 1). In contrast to cis-C-C double bonds formed in zhang@chem.ucsb.edu. Supporting Information Available: Experimental procedures, compound characterization data. This material is available free of charge via the Internet at http://pubs.acs.org. Rh-catalyzed decomposition of α-diazo carbonyl compounds,11 only trans-2a was observed, reflecting a unique aspect of gold carbene reactivities.
NIH Public AccessWith this encouraging result, we then chose non-symmetric aliphatic alkyne 1b to study regioselectivity by tuning the steric and electronic properties of gold catalysts and N-oxides. Table 1 shows some...