Hindered biaryl bond

Another total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B has been developed by Hoye et al. [32], who emphasized that Suzuki coupling of the boronic acid derived from the naphthalene moiety with a THIQ-iodide proved to be the most generally effective method for forming the hindered biaryl bond. A racemic isochromane analogue of michellamines has been synthesized by a similar procedure [33]. 

The hindered biaryls are examples of a different type of chiral compound due to their rotational restriction around a C C single bond. As long as the ortho-substituents in a compound such as 23 are bulky enough, the compound can exist in two forms, 23 and its enantiomer 23, which are not interconvertible. 

Buchwald et al. have reported a number of bulky phosphine ligand PR 2R which give high activity in Suzuki— Miyaura catalysis for the synthesis of sterically hindered biaryls.The conditions used in the catalysis involved the in situ preparation of the Pd(0) catalyst from Pd2(dba)3 and the phosphine. Two ligands which proved superior to the others had in common the same polyaromatic R (R = Cy, Ph) as a difference from the rest. A Pd(0) complex could be prepared by mixing Pd2(dba)s and PR 2R in toluene, which has the X-ray structure 40 sketched in the upper reaction of Scheme 25. The key structural feature of the complex is the short distance of Pd to one double bond of the phenanthrene moiety (distances to the two carbons are 2.298 and 2.323 A) supporting an 77 -phenanthrene... 

Mechanistic studies carried out by the Buchwald group97,98 on the key C-O bond formation step in these reactions have reinforced the importance of the properties of the ligand, and have led to the adoption of a variety of more sterically hindered ligands (e.g., 23, 24, 27, 29, and 30), which have given improved results for the preparation of biaryl ethers (Equation (15)),89 /-butyl aryl ethers,99 and aryl ethers of primary alcohols.100... 

Cis-trans isomerism around single bonds has been widely used in supramolecular chemistry, in particular with bulky biaryl compounds such as the metal-chelating agents bipyridines and sterically hindered binaphthyl motifs. In these compounds, a moderate barrier to rotation exists due to the resonance of the two con-... 

It is well known that transition metal-catalyzed carbon-carbon bond formations are extraordinarily difficult with sterically hindered, electron-rich aryl triflates.However, just such a transformation was required to install the Z-propenyl fragment necessary for the samarium-mediated cyclization. Lauren s initial attempts to achieve this goal afforded predominantly detriflated material and capricious reactions leading to loss of biaryl enantiopurity. 

As observed with carbene rotations (see Section 3), conformations of aryls can introduce additional chirality into a complex. Aryls prefer to lie orthogonal to the coordination plane in square-planar complexes. Hindered rotation of aryls in these complexes can produce atropisomerism, although this description is most commonly associated with restricted rotation about C-C single bonds in biaryls. An example of hindered rotation is found in (DIOP)Pt(3,5-Br2C6H3)(I) (43) in Brown s paper which provides an excellent discussion and leading references. The ortho protons of the dibromoaryl are... 

The control of stereochemistry with chromium carbine complexes has been reviewed. The DBR can create a new stereocenter in three ways. First, the arene tricarbonyl chromium complex contains a plane of chriality, thus the complexes 35 and ent-35 are enantiomers when RL Ri and RS R2. Second, when phenyl substituents are included in the reactants the resulting biaryls can posess axial chirality if there is hindered rotation about the new aryl-aryl bond as in 36. Finally, all DBRs with differentially p-disubstitued alkenes give rise to cyclohexadienones 37 with a new stereocenter adjacent to the carbonyl. When Ri and R2 are not hydrogen, tautomerization cannot occur and the final product possesses a chiral center. 

Axial chirality of biaryls, also known as the atropisomerism phenomenon, arises from hindered rotation around the central single bond (Scheme 5.4). 

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