A single Cu(II) catalyst without the addition of ligand or base couples a diverse range of nitrogen sources with alkynes and aldehydes bearing alkyl, halogenated, silyl, aryl, and heteroaryl groups. The first example of a copper-catalyzed alkynylation involving p-toluenesulfonamide provides high yields of N-Ts-protected propargylamines. The superior activity of copper(II) triflate also allows this three-component alkynylation to incorporate a ketone.

A high-yielding three-component reaction proceeds under mild, solvent-free conditions for access to a wide variety of fully-substituted propargylamines. Inexpensive copper(II) chloride catalyzes the coupling of equimolar amounts of amines, alkynes, and cyclohexanone such that the only byproduct is one equivalent of water.Scheme 1 Versatile KA 2 of cyclohexanone, amines, and alkynes. † Electronic supplementary information (ESI) available: Spectroscopic data and detailed procedures for all compounds are available online free of charge. See

The first ketone-catalyzed method for the oxidation of aliphatic C-H bonds is reported. The reaction conditions employ aryl trifluoromethyl ketones in catalytic amounts and hydrogen peroxide as the terminal oxidant. Hydroxylation is stereospecific and chemoselective for tertiary over secondary C-H bonds. A catalytic cycle invoking a dioxirane as the active oxidant is proposed.

A wide range of natural products and bioactive compounds contain fully substituted carbon centers. [1] To circumvent the difficulty of creating these hindered CÀN bonds in one step, compounds are commonly synthesized and rearrangement induced. [2] A catalytic system capable of overcoming the barrier to the condensation of a ketone and an amine to a ketimine, while leaving a nucleophile able to attack would lead to the direct formation of tetrasubstituted carbon atoms bearing amines. [3] In contrast to the wide array of threecomponent couplings (3CC) of aldehydes by the in situ formation of aldimines, reactions of ketones as electrophiles require an extra step that costs time, energy, and chemicals to produce and purify the ketimine starting material. [4] Dozens of enantioselective additions to ketimines have appeared without examples of the corresponding 3CC in either asymmetric or racemic form. [1] This situation suggests that the direct 3CC of ketones is more difficult to achieve than the asymmetric addition of nucleophiles to preformed ketimines.The nucleophilic attack on imines by terminal alkynes has been widely studied owing to the intrinsic biological activity and utility of the resulting propargylamines as synthetic building blocks. [5] Aldehyde-amine-alkyne couplings (A 3 ) abound, [6][7][8] but as ketones are 750-times less-active than aldehydes as electrophiles, [9] the corresponding KA 2 procedure for unactivated ketones has not been reported. The three catalytic methods developed for cyclohexanones [10][11][12] rely on the fact that they undergo nucleophilic attack 300-times faster than acyclic ketones. [13] Cyclohexanone is a special case of near aldehyde-like reactivity, [14] and its corresponding ketimines [15] readily react to release torsional strain. [16] Until Van der Eycken and co-workers described their solvent-free KA 2 methodology, [10] the catalytic incorporation of any ketone was an isolated, low-yielding event. [17] By applying microwave conditions in the presence of 20 mol % CuI, cyclohexanones and benzylamines couple with phenylacetylenes in 31-82 % yield. [10] Employing 4 mol % AuBr 3 , Ji and co-workers focused on cyclic amines and phenylacetylenes. [11] With 1 equivalent morpholine and 1.5 equivalents each of 2-pentanone and phenylacetylene, this Au III system produces what they term a quaternary propargylamine in 54 % yield.

The first examples of catalysis of aliphatic C-H hydroxylation by an iminium salt are presented. The method allows the selective organocatalytic hydroxylation of unactivated 3° C-H bonds at room temperature using hydrogen peroxide as the terminal oxidant. Hydroxylation of an unactivated 2° C-H bond is also demonstrated. Furthermore, improved functional group compatibility over other catalytic methods is reported in the form of selectivity for aliphatic C-H hydroxylation over alcohol oxidation. On the basis of initial mechanistic studies, an oxaziridinium species is proposed as the active oxidant.