Oxaphosphole‐Based Monophosphorus Ligands for Palladium‐Catalyzed Amination Reactions

Abstract

A novel class of C-2-substituted oxaphosphole-based monophosphines 1-4 has been synthesized. Palladium complexes derived from these ligands and their C-2-unsubstituted analogs provide general catalysts for amination reactions of challenging aryl and heteroaryl halides with sterically hindered anilines and alkylamines.

Heavily Substituted Atropisomeric Diarylamines by Unactivated Smiles Rearrangement of N‐Aryl Anthranilamides

“…[8] Nonetheless,d espite the existence of atropisomeric diaryl ethers 1 and 2 and diaryl sulfides 3,the potential for atropisomerism in diarylamines has hardly been explored. Thec hallenging N-arylations of 2,6disubstituted anilines by 2,6-substituted aryl halides (which require specialist ligands and techniques) [10] and the lack of generality in structures available by nucleophilic aromatic substitution (S N Ar) reactions prompted us to explore an alternative approach to 6.Smiles rearrangement allows N-arylation, under basic conditions,o fa mides, [11] carbamates, [12] anilines [13] and indoles. We now report the first example of an unelaborated diarylamine atropisomer 6, whose synthesis was made possible by the discovery of aremarkable unactivated Smiles rearrangement of anthrani-lamides 5.T his rearrangement allows the construction of diarylamines with exceptionally high steric hindrance.…”

“…Thec hallenging N-arylations of 2,6disubstituted anilines by 2,6-substituted aryl halides (which require specialist ligands and techniques) [10] and the lack of generality in structures available by nucleophilic aromatic substitution (S N Ar) reactions prompted us to explore an alternative approach to 6. [4a, 5] Expecting similar steric demands in atropisomeric diarylamines,w es ought synthetic methods allowing the construction of ArÀNb onds between 2,6disubstituted anilines 7 and 2,6-disubstituted coupling partners 8 (Scheme 1).…”

Recyclable Catalysts for Palladium‐Catalyzed Aminations of Aryl Halides

“…Based on their elegant work in the last two decades, transition-metal-catalyzed aminations of aryl halides as well as related substrates have become the most popular tool for their preparation on a laboratory scale. [5][6][7] Whereas easily activated substrates such as aryl iodides and activated bromides can be coupled with primary and secondary amines in the presence of a plethora of palladium and copper catalysts, more challenging substrates including heterocyclic arenes, aryl mesylates, and chlorides do require specifically designed ligands for successful coupling processes. It is generally accepted that sterically hindered and electron-rich mono-and bidentate phosphanes represent stateof-the-art ligands for the latter processes.…”

Sequential C–H Arylation and Enantioselective Hydrogenation Enables Ideal Asymmetric Entry to the Indenopiperidine Core of an 11β-HSD-1 Inhibitor

“…Fully aware of the challenges associated with the asymmetric hydrogenation of tetrasubstituted olefins, 9 we aspired to engineer a new catalytic system for this important transformation by leveraging our recently developed dihydrobenzooxaphosphole (BOP)-based ligand series ( vide infra ). 10,11 To access requisite hydrogenation precursor A , a conceptually concise sequence was devised involving an S N Ar coupling of fragments 4 and 5 followed by an intramolecular C–H arylation. At the outset, the proposed cyclization to the C-3 position of pyridine was expected to be challenging, with few related examples found in the literature.…”

“…10 Many effective ligands have been derived from this motif and have been found to mediate a variety of different catalytic transformations. 11 In particular, the rigid bidentate BoQPhos P,N-ligands, which were constructed from the BOP core by anchoring a less basic nitrogen-containing pyridine fragment onto the carbon atom of the O,P ring system (see Figure 4), have been successfully demonstrated for asymmetric hydrogenation of nonfunctionalized tri- and tetrasubstituted olefins. 6 Since the presumed final intermediate in the reduction of tricyclic substrate 13 contains a tetrasubstituted double bond (see compound 15 in Figure 3), we anticipated that the BoQPhos series would be applicable to the asymmetric reduction of 2,3-disubstituted pyridinium salts (Figure 4).…”