Discovery and synthesis of novel phosphine-based ligands for aryl aminations

BippyPhos: A Single Ligand With Unprecedented Scope in the Buchwald–Hartwig Amination of (Hetero)aryl Chlorides

“…Using these standard conditions, functionalized (hetero)aryl chlorides were successfully cross-coupled with a variety of amides and sulfonamides in synthetically useful yields (44-99 %, 4-1-4-23; Figure 6). Chlorobenzene was successfully cross-coupled under the standard conditions with amides (4-1, 4-9, 4-15) and sulfonamides (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Substi- www.chemeurj.org tution in the ortho-position was also tolerated and 2-chlorotoluene was successfully cross-coupled with amides (4-4, 4-14, 4-17).…”

“…Substi- www.chemeurj.org tution in the ortho-position was also tolerated and 2-chlorotoluene was successfully cross-coupled with amides (4-4, 4-14, 4-17). Electron-poor 4-chlorobenzotrifluoride was also cross-coupled with amides (4-3, 4-11, 4-16), sulfonamides (4- 21,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and formamide (4-23). Electron-rich 4-chloroanisole proved to be a more challenging coupling partner.…”

BippyPhos: A Highly Versatile Ligand for Pd‐Catalyzed C−N, C−O and C−C Couplings

“…The earliest work at Pfizer involved directed lithiation of heterocycles (Figure ). These initial ligands ( 1 , 2 and 3 ) explored showed modest reaction rates and relatively narrow substrate scope . A second family of ligands examined possessed a biaryl motif analogous to the Buchwald ligands (ligands 4 – 7 ), demonstrated improved turnover numbers, but still fell short of the reactivity of Buchwald ligands .…”

Phosphines and Related Tervalent Phosphorus Systems

“…37 Three distinct groups of functionalised phosphines, (14), (15), and the heteroarylphosphine (16), have been developed as ligands for palladium-catalysed aryl aminations, each system having been obtained by the reaction of aryllithium reagents with halogenophosphines. 38 Among other heteroarylphosphines prepared in this way are a series of 2-phosphino-N-aryl-pyrroles 39 and -indoles, 40 the diphosphinopyrazole (17), 41 and further examples of bis(phosphino)oligothiophenes. 42 A new approach to the 1-phosphabicyclo [3,3,0]octane system (18) starts from the Grignard reaction of 4-chloro-hepta-1,6-diene with magnesium in THF, which proceeds without rearrangement.…”

“…70 New phosphines based on other metallocene scaffolds have also been reported, including osmocene, 71 benzenechromium tricarbonyl, 72,73 and the related cyclopentadienylrhenium(I) tricarbonyl system. 74 (37) Organolithium reagents have been widely employed in the synthesis of new diphosphines, including chiral 2,2 0 -bis(phosphino)biphenyls, 76,77 a series of new diphosphine ligands based on bisphenol A backbones, e.g., (38), 78,79 various 2,2 0 -bis(phosphino)diphenylamines, 80,81 and the C 2 -symmetric trans-coordinating ligand 'SPANphos' (39). 82 The norbornene-based diphosphine (40) has been obtained and shown to undergo a ruthenium-catalysed metathesis polymerisation of the norbornene moiety to give the polymeric diphosphine (41).…”