Enantioselective construction of biaryl part in the synthesis of stegane related compounds

Abstract

A Pd-mediated intramolecular aryl-aryl coupling reaction of phenyl benzoate derivatives were examined to form benzo[c]chromen-6-ones, and then enantioselective lactone-opening reaction with a borane-oxazaborolidine combination was carried out. The resulting biphenyl was transformed into a key intermediate for the stegane related compounds. The absolute configuration of the biphenyl is also discussed. Stegane and related compounds are important because of their interesting biological activities such as antileukemic properties. 1 One of the most outstanding features of their chemical structures is an unsymmetrical 2,2'-disubstituted biphenyl moiety with an axial chirality (Figure 1). For the formation of such a biphenyl part in the syntheses of the stegane families, several approaches have been attempted such as photocyclization, 2 Suzuki coupling, 3 oxidative biaryl coupling, 4 the S N Ar reaction, 5 Ullmann coupling, 6

Atroposelective Synthesis of Axially Chiral Biaryl Compounds

“…The carboxy‐ and phenol‐derived ortho functions resulting from the ring‐opening do not necessarily have to be part of the product, as they can easily be transformed or removed (see 282 and 285 ). The lactone approach has also been used, among others, by Molander et al in the total synthesis of (+)‐isoschizandrin ( 283 )250 and by Abe, Harayama, and co‐workers in a formal total synthesis of (−)‐steganone (( M )‐ 107 ) 251. Severe limitations of the method are not yet known 253.…”

Recent Development in Palladium-Mediated Synthesis of Oxygen Heterocycles

“…Palladium-catalyzed intramolecular biaryl coupling of phenyl benzoate derivatives 71a,b was investigated. 56 The reactions of 71a,b in the presence of Pd(OAc) 2 , P(n-Bu) 3 and K 2 CO 3 in DMA under refluxing condition proceeded smoothly to give benzo[c]chromen-6-ones 72a,b (Scheme 22).…”

Atropselektive Synthese axial‐chiraler Biaryle

“…Die aus der Ringöff-nung resultierenden, von Carboxy-und Hydroxygruppen abgeleiteten Funktionalitäten in ortho-Stellung müssen nicht notwendigerweise Teil des Produkts sein (siehe 282 und 285), da sie leicht umgewandelt oder entfernt werden können. Die Lacton-Methode wurde unter anderem von Molander et al in der Totalsynthese von (+)-Isoshizandrin (283) [250] und von Abe, Harayama und Mitarbeitern in der formalen Totalsynthese von (À)-Steganon ((M)-107) [251] eingesetzt. Stärkere Einschränkungen der Methode sind nicht bekannt.…”