Expanding the Palette of Organic Synthesis in Water: I. Carbonyl Iron Powder as a Reagent for Nitro Group Reduction. II. B-alkyl Suzuki-Miyaura Couplings in Water. III. Development of a Low-Foaming Surfactant for Organic Synthesis in Water IV. “ppm” Tsuji-Trost Allylations in Water

I. In searching for a broadly applicable method for nitro group reduction in water, carbonyl iron powder (CIP) was identified as a commercially available source of Fe(0) which was uniquely suited to this task. The method was found to work well on substrates which were difficult to reduce by other means, and in a mild and environmentally friendly fashion, while ensuring good-to-perfect chemoselectivity. II. While much research has been conducted on Suzuki-Miyaura couplings in aqueous medium, very little exists in the synthetic literature related to B-alkyl Suzuki-Miyaura couplings conducted in water. A partially oxidized derivative of the venerable 9-BBN reagent was found to be especially suitable for B-alkyl Suzuki couplings in water. A general methodology for use of these “OBBD” reagents in water was developed, as well as studies on the bench stability and air tolerance of the coupling reactions themselves. III. The development of new “designer” surfactants specifically tailored to organic synthesis in water has been a reoccurring theme in Lipshutz Group for the last decade. In this chapter of surfactant development, we developed a new surfactant with low-foaming properties. This property of low-foaming is particularly important in reactions which produce gas, or otherwise introduce gas into the reaction medium, as this will cause a large reaction volume increase when conducted with “typical” surfactants. Several types of reactions which suffer from this gas-evolution problem are presented, as well as a number of other reaction types. The development of this surfactant, as well as reaction comparison trials are presented, as compared to what is considered benchmark-surfactant: TPGS-750-M. IV. The use of palladium catalysis has been ubiquitous in modern organic synthesis. However, with increasing palladium prices and a growing awareness of the endangered status of palladium as a precious metal, there is an ever-increasing move toward sustainable catalysis practices. In the simplest interpretation, this means using as low amounts of palladium as possible in coupling reactions. The study of palladium catalyzed allylic substitution reactions or “Tsuji-Trost” reactions under very low catalysts loadings is presented. A number of reaction types which have not been previously reported in water were explored, and the results of these explorations are presented. In addition to more “typical” reaction types like allylic aminations, some of these previously-not-known-to-water were found to be suitable at very favorable palladium loadings of 1000 ppm (0.1 mol%)