The Lactone Concept: An Efficient Pathway to Axially Chiral Natural Products and Useful Reagents

Abstract

$EVWUDFW A highly efficient concept for the stereoselective synthesis of axially chiral biaryl target molecules is presented: the atroposelective ring cleavage of configurationally unstable lactonebridged biaryls. The method has almost no restrictions concerning the substitution pattern, works even for substrates with high steric hindrance at the RUWKR-position(s) of the axis, and allows the optional, atropo-divergent preparation of each atropisomer from the same biaryl lactone precursor and a recycling of the undesired minor product in the sense of a chiral economy. A broad series of successful applications in natural product and ligand syntheses underlines the high value of the method. .H\ ZRUGV axial chirality, biaryl natural products, biaryl ligands and reagents, atropo-divergent synthesis, lactone-bridged biaryls '-BINAP' () R 7

Synthesis of Axially Chiral Biaryls by Atropo-Diastereoselective Cleavage of Configurationally Unstable Biaryl Lactones with Menthol-DerivedO-Nucleophiles

“…[9] Axially chiral biaryl compounds play an important role As nearly ideal model lactones without stereocenters for as useful ligands or reagents for asymmetric synthesis [1] and (overall) atropo-enantioselective ring-opening reactions, [4] [5] as pharmacologically potent natural products. [2] [3] A highly benzopyranones of type 4 (Scheme 2) can be easily conefficient strategy for the directed, i.e., regio-and atropose-structed from their monomeric "halves" by esterification lective synthesis of even complex and highly functionalized and Pd II -catalyzed intramolecular aryl coupling in excellent biaryls is the "lactone method", [4] [5] which is based on the yields. [4,10,11] Due to the steric demand of the substituent R atropisomer-differentiating ring cleavage of configura-ortho to the biaryl axis, the lactones 4 are helically distionally unstable lactone-bridged biaryls with chiral N-, O-torted, with rapid interconversion of the two enantiomeric and H-nucleophiles or, if additional stereocenters are pre-forms, (M)-4 [12] [13] and (P)-4.…”

“…[4,10,11] Due to the steric demand of the substituent R atropisomer-differentiating ring cleavage of configura-ortho to the biaryl axis, the lactones 4 are helically distionally unstable lactone-bridged biaryls with chiral N-, O-torted, with rapid interconversion of the two enantiomeric and H-nucleophiles or, if additional stereocenters are pre-forms, (M)-4 [12] [13] and (P)-4. [4] [10] With chiral hydride or sent in the molecule, also with achiral reagents. The broad isopropylate transfer reagents, these configurationally labile applicability of this principle has been demonstrated in the lactones 4 can be cleaved atropo-enantioselectively to give total synthesis of axially chiral catalysts [4] [6] and more than stereochemically stable target biaryls with good to excellent 20 naturally occurring biaryls, [2] [3] mainly naphthylisoquin-enantiomeric ratios (e.r.)…”

“…[4] [10] With chiral hydride or sent in the molecule, also with achiral reagents. The broad isopropylate transfer reagents, these configurationally labile applicability of this principle has been demonstrated in the lactones 4 can be cleaved atropo-enantioselectively to give total synthesis of axially chiral catalysts [4] [6] and more than stereochemically stable target biaryls with good to excellent 20 naturally occurring biaryls, [2] [3] mainly naphthylisoquin-enantiomeric ratios (e.r.) of up to 98.5:1.5.…”

Synthesis of All-Methylated Isorugosin B

“…Recently, we reported the stereoselective synthesis of a valoneic acid derivative, in which Bringmann's "lactone concept" [14][15][16][17][18] was used to form its optically active biphenyl moiety. 19) In this paper, based on our previous work, we report the synthesis of all-methylated isorugosin B (1) [20][21][22][23] ( Fig.…”

Remarkably diastereoselective synthesis of a chiral biphenyl diphosphine ligand and its application in asymmetric hydrogenation

“…Atropisomeric, C 2 -symmetric diphosphine ligands have played a particularly crucial role in the development of asymmetric catalysis (1)(2)(3)(4). Therefore, it is not surprising that considerable efforts have been taken for the design and synthesis of atropisomeric ligands based on the biphenyl, binaphthyl, or other biaryl backbones (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”