Synthesis Atropisomerism

The first examples of macrocyclization by enyne RCM were used in Shair s impressive biomimetic total synthesis of the cytotoxic marine natural product longithorone A (429) [180]. This unique compound features an unusual hep-tacyclic structure which, in addition to the stereogenic centers in rings A-E, is also chiral by atropisomerism arising from hindered rotation of quinone ring G through macrocycle F (Scheme 85). It was assumed that biosynthesis of 429 could occur via an intermolecular Diels-Alder reaction between [12]paracy-... 

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... 

As to most chiral atropisomeric ligand, resolution or asymmetric synthesis is requisite. Mikami developed a novel ligand-accelerated catalyst. The chirality of atropos, but achiral triphos ligand-Ru complex, can be controlled by chiral diamines. Using ( -dm-dabn as controller, the single diastereomeric triphos-Ru complex was achieved through isomerization of (i )-triphos-Ru complex in dichloroethane at 80 °G (Scheme l).44... 

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

The most formidable challenge in the synthesis of vancomycin is to maintain control of the atropisomerism displayed as a result of hindered rotation of the aromatic residues in each of the three cyclic tripeptide units (AB, C-O-D, D-O-E see structure 111, Scheme 21). The Evans and Nicolaou procedures are similar in that each focuses first on construction of the... 

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,... 

Synthesis of chiral atropisomeric diphosphine type ligands is a current challenge in chemical research because their late transition metal complexes usually provide high enantioselectivity in homogenous catalytic reactions. [28] In practical point of view, preparation and optical resolution of racemic diphosphine oxides followed by the reduction of the separated enantiomers are usually more advantageous than an expensive enantioselective synthesis of one diphosphine enantiomer. [29]... 

The Nicolaou group entered this area relatively recently, hence it is truly remarkable that they were able to develop a synthesis of the vancomycin aglycon so quickly. However, their route stumbles over the sections that involve atropisomeric selectivity or removal of the triazine. Evans group synthesis addresses or avoids these problems. It is a more polished effort that took many years and high levels of financial and human resources to develop. 

Ken D. Shimizu, Heather O. Freyer, Richard D. Adams Synthesis, resolution and structure of axially chiral atropisomeric N-arylimides, Tetrahedron Lett. 41,5431-5434 (2000)... 

Direct synthesis of atropisomeric benzamides and anilides from prochiral precursors has been reported using chiral-amide-mediated deprotonation of 2,6-dimethyl-substituted ben-zamide and anilide chromium complexes. A screening of amides revealed that (R,R) 3 was the most selective in the deprotonation of the benzylic methyl groups (Scheme 51)92 94. 

The potassium enolate generated from 23 is regarded as an enantiomeric atropisomer. Recently non-biaryl atropisomers have been receiving more attention in asymmetric synthesis.19 Most of them employ atropisomers that are configurationally stable at room temperature, while attention in this chapter is focused on asymmetric reactions that proceed via chiral nonracemic enolate intermediates that can exist only in a limited time. An application of configurationally stable atropisomeric amide to a chiral auxiliary for stereoselective alkylation has been reported by Simpkins and co-workers (Scheme 3.10).20... 

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