Relativistic Functional Groups: Aryl Carbon–Gold Bond Formation by Selective Transmetalation of Boronic Acids

Abstract

The rational design of triplet-state sensitizers for the photodynamic therapy of cancers [1][2][3] and other diseases [4] remains an obdurate challenge. A prominent strategy [5][6][7] is the modification of existing photosensitizers with bromine (Z = 35) or iodine (Z = 53); the resulting heavy-atom effects potentiate the generation of therapeutic 1 D g O 2 . The (phosphane)gold(I) fragment is s-isolobal with the proton. Terminal substitution of aromatic organic molecules with gold (Z = 79) has clear desirability for developing phototherapy mediators. What is missing are mild means of carbon-gold bond formation in the presence of sensitive functional groups. We describe here a selective protocol that installs gold(I)-carbon bonds along the peripheries of organic molecules. Reducible, polar moieties are tolerated, including nitro groups, aldehydes, ketones, and esters. The organometallic compounds described here withstand air and water indefinitely. The ability to modify organic fluorophores with gold raises immediate opportunities in metallopharmaceuticals design. [8][9][10] Finally, the new protocol affords organogold(I) compounds more rapidly and in higher yield than by traditional methods [11] of arylating gold. In the palladium-catalyzed Suzuki-Miyaura cross-coupling, [12,13] carbon-carbon bond formation is believed to follow transmetalation from boron to palladium. The reaction often requires an auxiliary base, which is thought to quaternize boron and promote transmetalation.[14] Related precedents include observations by the groups of Schmidbaur [15] and Fackler [16] of phenyl-group transfer from BPh 4 À to gold(I) in aqueous and non-aqueous media.[*] Dr.

Mono- and Di-Gold(I) Naphthalenes and Pyrenes: Syntheses, Crystal Structures, and Photophysics

“…8 Earlier publications by Fackler, Schmidbaur, and their co-workers documented phenyl group transfer to gold(I) from tetraphenylborate anion. 27,28 An example is 1-naphthyl group transfer to a (phosphine)gold(I) bromide, eq 1:…”

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

“…In 1998 we introduced a new class of air-stable [1] phosphine ligands based on the dialkylbiaryl phosphine backbone. [2] These phosphines have been used as ligands for gold, [3][4][5][6][7][8][9][10][11] silver, [12] rhodium, [13,14] ruthenium [15][16][17] and copper [18] where they have been shown to impart improvements in reactivity and catalyst stability. It is in reactions catalyzed by palladium, however, that they have had by far the greatest impact including the Sonogashira, [19] Negishi, [20] Hiyama, [21][22][23] Kumada [24] and Suzuki [25][26][27][28][29][30] cross-coupling reactions, Heck reaction, [31][32][33] enolate arylation [34][35][36][37] and allylation, [38] reductive cyclization [39] and etherification, [40][41][42][43] silylation, [44] borylation, [45]…”

Gold-Containing Indoles as Anticancer Agents That Potentiate the Cytotoxic Effects of Ionizing Radiation

“…Phosphine-gold(I) organometallics were prepared in transmetallation reactions developed by Gray and co-workers. 31–33 Protecting groups were added to N1 of indole to prevent coordination at nitrogen. The starting reagent is an indole boronic acid or pinacol boronate ester.…”