Biaryls atropisomerism

Enantioselective lithiation can be used to introduce and control new elements of planar or of axial chirality. The principal classes of compounds displaying these stereochemical features are ferrocenes, arenechromium tricarhonyl complexes, biaryls, atropisomeric amides and al-lenes. Methods for the enantioselective lithiation of these compound classes, relying on either substrate (chiral auxihary) or reagent (chiral base) control will be reviewed. 

Finally, the Miller group developed a peptide-catalyzed electrophilic aromatic substitution reaction (Scheme 13.34) [71]. Remarkably, this transformation resulted in a dynamic kinetic resolution (DKR), in which a single atropisomeric product was produced from interconvertible (i.e., racemic) biaryl atropisomeric starting materials. 

See reference [45] for a study of atropisomerization thresholds for model biaryls and perylenequinones. 

Chan has discovered a completely atropdiasteroselective synthesis of a biaryl diphosphine by asymmetric intramolecular Ullmann coupling or Fe(m)-promoted oxidative coupling. A chiral atropisomeric biaryl bisphosphine ligand 2 was synthesized through this central-to-axial chirality transfer.38 Recently, a xylyl-biaryl bisphosphine ligand, Xyl-TetraPHEMP, was introduced by Moran, and is found to be effective for the Ru-catalyzed hydrogenation of aryl ketone.39... 

This chapter describes atropisomeric biaryl bisphosphine ligands modified DIOP-type ligands P-chiral bisphosphane ligands other bisphosphane ligands and their applications in the enantioselective hydrogenation of olefins. 

SCHEME 32. Pd-catalyzed enantioposition-selective synthesis of atropisomeric biaryls... 

Diastereo- and enantio-selectivity in nucleophilic aromatic substitution is limited to atropisomerism in binaphthyl- and biaryl-forming reactions.21-42... 

Atropisomeric biaryl bisphosphines, in hydrogenation, 10, 2 Atropisomerism, dynamic NMR studies, 1, 421 ATRP, see Atom transfer radical polymerization type reactions rj3-l-Azaallyl complexes, with nickel, 8, 158 6-Aza[3.2.1]bicyclooct-3-ene, via ring-closing metathesis,... 

Biaryl bisphosphines, atropisomeric, in hydrogenation, 10, 2 Biaryl-bridged bis(iminooxazolidine) complexes, with Zr(IV) and Hf(IV), 4, 811-812 Biaryl compounds, directed synthesis, 10, 145 Bicyclic arenes, in hexaruthenium carbido clusters,... 

The reaction is quite sensitive to the chiral ligand used. Diphosphines with an axially disymmetric biaryl moiety in the backbone give the best results. The effectiveness of p-Tol-BINAP as ligand, for example, is similar to that of BINAP. The related atropisomeric ligand BIPHEMP can also be used [9]. Among chiral aliphatic diphosphines tested, CyDIOP, which only differs from DIOP in the type of P-substituents, also gives satisfactory results. 

The highly efficient stereoselective transformations catalyzed by transition metals that contain BINAP have resulted in extensive efforts in the development of both new Ru-BINAP catalysts and chiral atropisomeric bisphosphines based on biaryl backbones and biheteroaryl backbones.49 Coupled with the various classes of Ru(BINAP) catalysts and chiral bisphosphines, the number of efficient industrial asymmetric hydrogenations are sure to increase because optimization for fine precision and easy optimization in catalyst activity and enantioselectivity made easier.57 66... 

The binaphthyl backbone of BINAP has inspired many variations of atropisomeric biaryl bisphosphines. One approach by Roche was to substitute the binaphthyl backbone with a 6,6 -dimethox-ybiphenyl backbone. MeO-Biphep (96a) was synthesized in approximately 26% yield in 6 steps from 3-bromoanisole (97a) (Scheme 12.30). MeO-Biphep can also be synthesized in 5 steps from 2-iodo-3-nitroanisole in approximately 18% yield. Several phosphine analogues can be prepared by the addition of R2PC1 to the lithio intermediate.117... 

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