Present work - -
Metal-free applications of diaryliodonium salts
We are currently working on development of metal-free reactions where diaryliodonium salts are employed as electrophilic arylation reagents with a range of nucleophiles. We have recently reported the efficient synthesis of diaryl ethers by arylation of phenols at room temperature.
We have also developed a synthesis of aryl esters by arylation of carboxylic acids, which allows production of extremely sterically hindered products.
Asymmetric α-substitution of carbonyl compounds is an interesting field, as the products obtained can be derivatized into so many functional groups and thus be of vast use in industry. Asymmetric α-arylation of enolates is investigated using a number of strategies. We have recently published a mechanistic study of this reaction.
We have also designed and synthesized chiral diaryliodonium salts in an asymmetric fasion, the use of which will be reported separately.
Synthesis of diaryliodonium salts
Diaryliodonium salts belong to the class of iodine(III) compounds. These non-toxic reagents can be employed in α-arylation of carbonyl compounds, metal-catalyzed cross couplings and as photo initiators. Present synthetic routes to diaryliodonium salts generally consist of 2-3 steps, often with an anion exchange.
We have recently developed several practical one-pot protocols towards diaryliodonium salts starting from aryl iodides and arenes. The oxidant of choice is mCPBA, which rapidly oxidizes the aryl iodide to iodine(III) intermediate. In the presence of an acid, the arene subsequently attacks this intermediate to form the diaryliodonium salt. The anion has an effect on the solubility and reactivity of the salt, and it is therefore of interest to develop routes to salts containing various anions.
When triflic acid (TfOH) is added to the reaction, diaryliodonium triflates are obtained in high yields, without the need for an anion exchange step. The reaction is fast and has a big substrate scope, leading to both symmetric and unsymmetric salts.
This protocol was subsequently extended to the reaction of molecular iodine with arenes. The method delivers symmetric diaryliodonium triflates in high yields and short reaction times, thus avoiding the need for expensive aryl iodides. The reaction can easily be performed on large scale.
Tosic acid (TsOH) can be employed in the same type of one-pot reaction, leading to diaryliodonium tosylates. The benefit of using tosic acid in some cases is that very electron-rich substrates are tolerated. In applications where the triflate anion is preferred to the tosylate, an in-situ anion exchange can be employed to obtain also electron-rich diaryliodonium triflates.
An alternative approach to diaryliodonium salts was subsequently developed. This sequential one-pot synthesis employs aryl iodides and arylboronic acids, which in the presence of mCPBA and BF3 deliver diaryliodonium tetrafluoroborates in a regiospecific manner, avoiding the EAS limitations of the two other protocols.
The synthesis of diaryliodonium triflates can also be performed using the environmentally benign oxidant hydrogen peroxide.
Synthesis of other iodine(III) compounds
We have reported the facile synthesis of Koser's reagent (HTIB), and substituted derivatives, directly from iodine and arenes or iodoarenes.
We have developed one-pot routes to a series of iodine(III) compounds from iodoarenes and mCPBA, delivering both alkynyl(aryl)- and alkenyl(aryl)iodoonium salts.
Diaryliodonim salt applications by other research groups
A number of interesting applications have been published recently. Here are some nice references; most of which employ our methodology to synthesize the diaryliodonium salts.
- A. Bigot, A. E. Williamson, M. J. Gaunt: "Enantioselective alfa-Arylation of N-Acyloxazolidinones with Copper(II)-bisoxazoline Catalysts and Diaryliodonium Salts" J. Am. Chem. Soc. 2011, 133, 13778. PDF
- J. S. Harvey, S. P. Simonovich, C. R. Jamison, D. W. C. MacMillan "Enantioselective alfa-Arylation of Carbonyls via Cu(I)-Bisoxazoline Catalysis" J. Am. Chem. Soc. 2011, 133, 13782. PDF
- A. E. Allen, D. W. C. MacMillan: "Enantioselective alfa-Arylation of Aldehydes via the Productive Merger of Iodonium Salts and Organocatalysis" J. Am. Chem. Soc. 2011, 133, 4260. PDF
- A. M. Wagner, M. S. Sanford: "Palladium-Catalyzed C-H Arylation of 2,5-Substituted Pyrroles" Org. Lett. 2010, 13, 288. PDF
- C.-L. Ciana, R. J. Phipps, J. R. Brandt, F.-M. Meyer, M. J. Gaunt: "A Highly Para-Selective Copper(II)-Catalyzed Direct Arylation of Aniline and Phenol Derivatives" Angew. Chem. Int. Ed. 2010, 50, 458. PDF
- H. A. Duong, R. E. Gilligan, M. L. Cooke, R. J. Phipps, M. J. Gaunt: "Copper(II)-Catalyzed meta-Selective Direct Arylation of α-Aryl Carbonyl Compounds" Angew. Chem. Int. Ed. 2010, 50, 463. PDF
- Robert J. Phipps and Matthew J. Gaunt: "A Meta-Selective Copper-Catalyzed C–H Bond Arylation" Science 2009, 323, 1593-1597. PDF
- Robert J. Phipps, Neil P. Grimster and Matthew J. Gaunt: "Cu(II)-Catalyzed Direct and Site-Selective Arylation of Indoles Under Mild Conditions" J. Am. Chem. Soc. 2008, 130, 8172. PDF
- Jean-Michel Becht and Claude Le Drian: "Biaryl Synthesis via Decarboxylative Pd-Catalyzed Reactions of Arenecarboxylic Acids and Diaryliodonium Triflates" Org. Lett. 2008, 10, 3161-3164. PDF
- Nicholas R. Deprez, Dipannita Kalyani, Andrew Krause, and Melanie S. Sanford: "Room Temperature Palladium-Catalyzed 2-Arylation of Indoles" J. Am. Chem. Soc. 2006, 128, 4972-4973. PDF