Atropisomeric Phosphine Ligands Bearing C-N Axial Chirality: Applications in Enantioselective Suzuki-Miyaura Cross-Coupling Towards the Assembly of Tetra-ortho-Substituted Biaryls.

Biaryl phosphines bearing C(Ar)-C(Ar) axial chirality are commonly known and have been successfully applied in many asymmetric catalyses. Nevertheless, the development of a chiral ligand having an axially chiral C(Ar)-N backbone remains elusive due to its undesirable less restricted rotational barrier. In fact, it is highly attractive to overcome this challenge in ligand development as the incorporation of an N-donor component at the chiral axis is more favorable toward the transient metal coordination, and thus, a better outcome of stereocommunication is anticipated to the approaching substrates. Herein, we present a rational design of a new collection of chiral phosphines featuring a C-N axial chirality and their applications in enantioselective Suzuki-Miyaura cross-coupling for accessing highly steric hindered tetra-ortho-substituted biaryls (26 examples up to 98:2 er). It is worth noting that the embodied carbazolyl framework is crucial to succeed the reaction, by the fruitful steric relief of bulky substrate coordination and transmetalation via a fleeting Pd-N jumping to Pd-π fashion. DFT calculation reveals an interesting Pd-arene-walking characteristic across the carbazolyl plane for attaining a lower energy-preferred route in a catalytic cycle. The theoretical study successfully predicts the stereooutcome and matches the enantioselectivity with the experimental results.

N-Difluoromethylation of N-pyridyl-substituted anilines with ethyl bromodifluoroacetate.

A general protocol for N-difluoromethylation of aniline derivatives is developed. Commercially available ethyl bromodifluoroacetate serves as a difluorocarbene source in the presence of a base. This carbene surrogate is attractive owing to its favorable stability, environmental friendliness and inexpensiveness. This reaction system features notable operational simplicity (bench top-grade solvents can be used without any pre-drying and do not require inert atmosphere protection). A wide range of functional groups in aniline derivatives are well-tolerated, and good-to-excellent product yields are generally obtained.

A Metal-Free and Redox-Neutral Benzylic C-O Cyclization for Succinct Access of Helical Chromenes.

A redox-neutral benzylic C-O cyclization under beneficial transition-metal-free conditions is reported. Key to the success of this process is the utilization of the Tf anion as the leaving group for achieving the redox-neutral transformation. This protocol delivers a series of captivating helical compounds having various functionality in good-to-excellent yields. It is particularly noteworthy that sterically hindered helical compounds are conformationally stable. In addition to simple helical chromenes, the bihelical multiple-ring systems which are potentially useful in material chemistry are also easily attained by employing this method. DFT calculation revealed that quinone intermediate is the key species, among four possible mechanisms, for accomplishing the desired cyclization via an oxa-6π-electrocyclization pathway.