Cross-coupling reactions between lipophilic terminal alkynes and aryl bromides can be catalyzed by ligated Pd, in the absence of copper, in pure water at ambient temperatures. Small amounts of the nonionic amphiphile PTS assist by virtue of nanometer micelles formed spontaneously in an aqueous medium.

Unsymmetrical di-and triarylamines can be formed under green chemistry conditions, taking advantage of micellar catalysis leading to palladium-catalyzed aminations at ambient temperatures in water as the only medium. Keywords aminations; amphiphiles; micellar catalysis; surfactantsThe direct amination of aromatic rings via palladium-catalyzed processes could be considered among the most important of the advances in synthesis within the past two decades. A wide range of C-N bond-forming reactions are available; a variety of aryl-, [1] heteroaryl-, [2] and alkylamines [3] can be introduced onto an aromatic or heteroaromatic ring. The nature of the leaving group also varies widely (e.g., halides, pseudo-halides, etc.), made possible by the impressive range of ligands developed that allow for fine-tuning of the reactivity of this group 10 metal.[4] Notwithstanding these impressive advances, there remain opportunities to further this science, in particular concerning the "greening" of existing procedures; [5] that is, finding new inroads to net aminations of aromatic rings that may be environmentally more appealing relative to existing methodologies. One such approach is to eliminate the up-front use of organic solvents, as well as the need to invest energy in the form of heat. A literature precedent for such amination reactions that fulfill these criteria (i.e., reactions in water only, at room temperature) is unknown.Aminations in water at reflux, on the other hand, have been reported, [6] as have such couplings in toluene/water using a phase-transfer catalyst, [7] and in "water-containing solvent." [8] Very recently, a limited amount of water has been found to assist with Pd catalyst pre-activation, although the catalysis was conducted in t-BuOH or dioxane at 110°C. [9] In this communication we describe the first amination technology for preparing unsymmetrical di-and triarylamines that relies on water exclusively as the medium at ambient temperatures (Scheme 1).Prior work has led to the finding that micellar catalysis,[10] based on the commercially available[11] "designer" surfactant PTS (polyoxyethanyl α-tocopheryl sebacate, 1; Figure 1) Table 1 (entries A-J). Importantly, these basic conditions did not lead to any saponification of the diester linkages that characterize PTS. Tertiary amine 5 could be fashioned at room temperature in three hours using these green conditions (water, 2% PTS) in good isolated yield (84%; Scheme 3). By way of comparison, the identical coupling using the most recent literature procedure for such aminations calls for a 20-hour timeframe in hot (100 °C) organic solvent (DME).[17]A simple switch from KOH to tert-butoxide [18] or t-amylate [19] (either K + or Na + ) had a dramatic impact on the rates of these aminations. At first, this might seem odd, given the leveling effect in water. However, these more lipophilic bases, to the extent present in water, would be expected to have far greater solubility than hydroxide within the lipophilic core of PTS micelles where the couplin...

Di-p-chlorobenzyl azodicarboxylate (DCAD) is introduced as a novel, stable, solid alternative to DEAD and DIAD for a variety of Mitsunobu couplings. DCAD/Ph(3)P-mediated reactions in CH(2)Cl(2) generate a readily separable hydrazine byproduct. [reaction: see text]

Alkynes Q 0087 Sonogashira Couplings of Aryl Bromides: Room Temperature, Water Only, No Copper. -With PTS as the nanomicelle-forming agent, the title reaction proceeds in pure water. A broad spectrum of water-insoluble aryl bromides and alkynes can be transformed without the use of any organic solvent or copper salts. -(LIPSHUTZ*, B. H.; CHUNG, D. W.; RICH, B.; Org. Lett. 10 (2008) 17, 3793-3796; Dep. Chem. Biochem., Univ. Calif., Santa Barbara, CA 93106, USA; Eng.) -R. Simon 02-075

Dehydration O 0336Simplification of the Mitsunobu Reaction. Di-p-chlorobenzyl Azodicarboxylate: A New Azodicarboxylate. -A variety of inter-and intramolecular Mitsunobu coupling reactions can be performed using DCAD as a novel, stable and solid alternative reagent to DEAD and DIAD. In methylene chloride, it is reduced to a separable hydrazine by-product which can be removed from the reaction mixture by precipitation with CH2Cl2. The yields of the coupling products and the reaction rates are similar for all three azodicarboxylates. -(LIPSHUTZ*, B. H.; CHUNG, D. W.; RICH, B.; CORRALL, R.; Org. Lett. 8 (2006) 22, 5069-5072;