Diastereoselective Ring Opening of Achiral Bridged Biaryls Using ChiralO- andN-Nucleophiles: First Atropo-Enantioselective Synthesis of (-)-4,4′-Bis(orcinol)¹

Atropo-Enantioselective Synthesis of the Natural Bicoumarin (+)-Isokotanin A via a Configurationally Stable Biaryl Lactone

“…It was planned to prepare this bridged biaryl from the bromo ester 6 as a single monoaryl precursor. The ( P ) enantiomer of 4,4′‐bisorcinol (biaryl 4 in its deprotected, tetraphenolic form) had already been prepared earlier, via a six‐membered lactone, although with only moderate atropo‐diastereoselectivity in the ring‐cleavage step (up to 48% de ) 6. Later, ( M )‐ 4 was used as an intermediate in Lin’s synthesis of (+)‐isokotanin A ( 1 ) 3…”

“…[α] D 25 = −36.7 ( c = 0.50, ethanol), ref 25. [α] D 20 = −41.3 ( c = 3.00, ethanol), ref 6. [α] D 25 = −38.6 ( c = 0.28, ethanol)}.…”

Dynamic Kinetic Resolution of Biaryl Lactones via a Chiral Bifunctional Amine Thiourea-Catalyzed Highly Atropo-enantioselective Transesterification

“…Notably, this protocol is operated under very mild conditions and delivers axially chiral biaryl products in high yields and with excellent enantio­selectivities (up to quantitative yields and 99% ee). Moreover, the process shows a much broader substrate scope than that of previous studies. , A variety of alcohols, including aliphatic alcohols and even phenols, perform very well. Moreover, biaryl lactones with a broad range of substituent patterns are efficienty transformed to chiral biaryl products.…”

“…However, achieving highly atropo-enantio­selective DKR of Bringmann’s lactones presents a long-standing challenge in synthesis, despite more than 20 years’ effort by Bringmann and Yamada and others. ,,,, Diastereo­selective transesterification of lactones with alcohols represents a straightforward approach to chiral biaryls but has had limited success so far. Chiral (+)-menthol-derived potassium alcoholate as chiral nucloephile gave the best result, with 48% ee (Scheme , eq 1, asymmetric transamidation giving better enantio­selectivity (86% ee)) . An asymmetric catalytic version using methanol as nucleophile by a chiral BINAP silver complex delivered moderate enantio­selectivity (50–84% ee, Scheme , eq 2).…”

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

“…[8] Preliminary investigations revealed the potential of This goal was not reached by later intermolecular biaryl atropo-diastereoselective lactone-cleavage reactions with chiral alkoxides as O-nucleophiles. [17] In this paper, we de-[ ] Part 79: Ref. [16] [a] Institut für Organische Chemie der Universität Würzburg scribe highly efficient atropo-enantioselective biaryl synth- thesized atropo-diastereo-or -enantiodivergently from the KH, leading to clear solutions of the alkali metal (1S)-mentholates (S)-7b, c, and d in the solvents used (THF, CH 2 Cl 2 , same lactone precursor 4, by simply using the appropiate mentholate R*OM or its enantiomer ent-R*OM; "wrong" Et 2 O, and toluene).…”