Asymmetric Synthesis of Gonytolide A: Strategic Use of an Aryl Halide Blocking Group for Oxidative Coupling

Abstract

The first synthesis of the chromanone lactone dimer gonytolide A has been achieved employing vanadium(V)-mediated oxidative coupling of the monomer gonytolide C. An o-bromine blocking group strategy was employed to favor para- para coupling and to enable kinetic resolution of (±)-gonytolide C. Asymmetric conjugate reduction enabled practical kinetic resolution of a chiral, racemic precursor and the asymmetric synthesis of (+)-gonytolide A and its atropisomer.

Synthetic Applications of Oxidative Aromatic Coupling—From Biphenols to Nanographenes

“…In this case, the reaction outcome is undoubtedly governed by the bulky O i Pr group, which enforces the dominant para – para coupling. Such a regioselectivity can also be achieved by blocking the ortho positions relative to the OH group, as was recently shown by Porco and co‐workers …”

“…In this case,t he reaction outcome is undoubtedly governed by the bulky OiPr group,which enforces the dominant para-para coupling.S uch ar egioselectivity can also be achieved by blocking the ortho positions relative to the OH group,aswas recently shown by Porco and co-workers. [21] Theo xidative dimerization of larger phenols represents one of the most convenient pathways toward complex 2,2'dihydroxybiaryl compounds.According to the Tsubaki group, butterfly-shaped molecule 11 can be obtained by the Cu IImediated dimerization of dinaphthofuran-6-ol ( Figure 2). [22] Thedihedral angle between the two central naphthyl moieties can be altered by chemical modification of the central region; for example,acid-catalyzed dehydration involving the central OH groups delivers an additional furan system, which in turn decreases the dihedral angle from 86.48 8 to 14.68 8,aspredicted by DFT methods.T he protected 1,1'-bi-2-pyrenol (12, Figure 2) can be prepared by the Fe III - [23] or Cu II -mediated [24] oxidative dimerization of the protected precursor of 2pyrenol.…”

Enantioselective Total Synthesis of Chromanone Lactone Homo‐ and Heterodimers

“…Examples for dimeric chromanone lactones are blennolide H ( 7 ) from Alternaria sp., and phomopsis‐H76 A from Phomopsis sp., which have been synthesized this year (2018) for the first time allowing the determination of their relative and absolute configuration . Quite recently the preparation of an additional natural homodimeric chromanone lactone has been described …”

“…[14] Quite recently the preparation of an additional natural homodimeric chromanone lactone has been described. [15] On the other hand, the configuration of several otherc ompounds of this type, especially those with ah eterodimeric structure as paecilin A( 8)f rom Paecilomyces sp. [10] and paecilin C( 9)f rom Penicillium sp (Figure 3).…”

Synthesis and Anticancer Activity of Structure Simplified Naturally Inspired Dimeric Chromenone Derivatives

“…The limited investigations dedicated toward advancing their biological performance in the context of drug discovery can be, at least in part, attributed to the synthetic challenges that naturally occurring dimeric chromanones and tetrahydroxanthones present . The chromanone and/or xanthone units of these dimers can be bonded in several scenarios, including scaffolds that contain 8,8′‐, 6,6′‐, and 6,8′‐linked chromenone/xanthone units (for the purposes of this paper a chromanone numbering scheme has been adopted, A – C , Figure ).…”