The Asymmetric Suzuki Coupling Route to Axially Chiral Biaryls

Abstract

Axially chiral biaryls are ubiquitous structural motifs in biologically active natural products or ligands for homogeneous catalysis. Their properties relate to the particular spatial arrangement of the two aromatic residues and therefore the control of their absolute configuration constitutes an issue of major importance. The asymmetric Suzuki–Miyaura coupling has recently emerged as an attractive alternative to standard methods for the control of biaryl axial chirality. Recent diastereo‐ and enantioselective approaches, as well as some applications in target‐oriented synthesis, are commented on in this microreview. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Efficient Synthesis of Chiral 1,1′‐Binaphthalenes by the Asymmetric Suzuki–Miyaura Reaction: Dramatic Synthetic Improvement by Simple Purification of Naphthylboronic Acids

“…, which is easily available by standard methods from the commercially available (R)-(+)-(1-ferrocenylethyl)-dimethylamine, [20] as well as three other (R,S p )-chiral ferrocenylmonophosphanes (9)(10)(11). Prior to optimization of the enantioselectivity tests, some studies were carried out in order to solve problems of reactivity encountered in the early stages of this study (Table 1).…”

“…In spite of this, though, a thorough examination of the literature afforded only a very few studies of Suzuki-Miyaura couplings in enantioselective catalytic asymmetric syntheses of binaphthalenes, hindered aryls, and related systems. [9] The first, and so far best (in terms of asymmetric induction), Suzuki-Miyaura syntheses of chiral binaphthalene derivatives were reported by Cammidge and CrØpy in 2000, and included-as the most hindered synthesis-that of 2,2'-dimethyl-1,1'-binaphthalene in 60 % yield and up to 85 % enantiomeric excess, through the use of PdCl 2 , boronic ester as nucleophile, and 2-(diphenylphosphinoferrocenyl)ethyldimethylamine as catalyst. [10,11] Sadly, this procedure has serious drawbacks that are discussed below.…”

A C3‐Symmetric Palladium Catalyst with a Phosphorus‐Based Tripodal Ligand

“…The enantiomerically pure complex was tested for the asymmetric cross-coupling reaction between 1-iodo-2-methoxynaphthalene and 1-naphthylboronic acid, which led to compound 7 with only 7 % ee. Despite the growing success of the Suzuki cross-coupling reaction for the construction of biaryls, its asymmetric variant still remains a challenge, [11][12][13] probably because of the inherent difficulty in coupling two sterically hindered arenes in a transition-metal-mediated process. Enantioselective couplings [13] have recently emerged as viable and more direct alternatives, thanks to the design of chiral ligands.…”

Asymmetric Synthesis of Antimicrotubule Biaryl Hybrids of Allocolchicine and Steganacin

“…[20] In particular, we described the asymmetric synthesis of a potent analogue of another axially chiral tubulin-binding biaryl compound, rhazinilam, through an atropo-enantioselective coupling catalyzed by palladium and a chiral phosphane ligand. [21] Herein, we report the synthesis of hybrid analogues of 2 and 4 using a complementary approach, namely, an atropo-diastereoselective Suzuki coupling [20] and the preliminary biological evaluation of these compounds as novel antimicrotubule agents. [22] Results and Discussion Retrosynthetic analysis and initial studies: In light of the similar structural properties and antimicrotubule activities of both types of natural products, we envisaged the synthesis of hybrid analogues 5 that retained the polyoxygenated biaryl backbone with the aR absolute configuration, namely, the common pharmacophore elements, but with bridging rings of varying size and substitution (Scheme 2).…”

“…[20,23,24] The stereogenic center in 10 should be preferably installed by a catalytic enantioselective reaction to render this synthetic sequence Abstract in French: La synthse asymØtrique de nouveaux biaryles à chiralitØ axiale 5 a-f, contenant un hØtØrocycle mØdian à sept ou huit chaînons, est dØcrite. Ces molØcules peuvent Þtre considØrØes comme des hybrides structuraux de produits naturels de type allocolchicine et stØganacine.…”