A Flexible Approach to 6,5‐Benzannulated Spiroketals

Abstract

A novel route to simple 6,5‐benzannulated spiroketal analogues has been developed. A convergent Horner–Wadsworth–Emmons olefination enabled ready assembly of the spiroketal precursors. Use of a benzyl protecting group strategy enabled an efficient one‐pot hydrogenation/deprotection/spiroketalisation process to be employed providing a robust method to access a range of substituted aromatic monobenzannulated spiroketals.

Synthesis of 5,6- and 6,6-Spirocyclic Compounds

“…Alternatively, using a benzyl ether-protecting group, an efficient tandem hydrogenation/deprotection/cyclization sequence was demonstrated [53] (Scheme 10). Direct hydrogenation of the HWE products unmasks the dihydroxyketones from which the mono(benzannulated) spiroacetals 36 are derived.…”

“…A more efficient approach [53] involved Horner-Wadsworth-Emmons (HWE) union of the phosphonates 27 with aromatic aldehyde 28 to give the cyclization precursors 29 in generally high yield (Scheme 9). Chemoselective reduction followed by treatment with either DDQ or 1 M HCl then afforded the spiroacetals 30-32.…”

“…Scheme 8 Kulinkovich coupling/ring-opening strategy toward mono(benzannulated) spiroacetals [52] Scheme 9 HWE/chemoselective reduction strategy toward mono(benzannulated) spiroacetals [53] Scheme 10 HWE/deprotection strategy toward mono(benzannulated) spiroacetals [53] A recent example of the use of dehydrative spirocyclization for the synthesis of a heteroannulated spiroacetal natural product is Sudhakar et al's synthesis of the acortatarins 37 and 38 [54] (Scheme 11).…”

2011 Royal Australian Chemical Institute National Award Winners

“…Brimble’s research focuses on the synthesis of bioactive natural products as novel anticancer, antibacterial, and antiviral agents, the synthesis of alkaloids and peptidomimetics for the treatment of neurodegenerative disorders, and the synthesis of peptide and glycopeptide components for melanoma vaccines. She has reported on the total synthesis of paecilospirone in Angewandte Chemie ,5a and on the synthesis of 6,5‐benzannulated spiroketals in the European Journal of Organic Chemistry 5b…”

Die Preisträger der Auszeichnungen 2011 des Royal Australian Chemical Institute

“…Im Mittelpunkt von Brimbles Forschung stehen die Synthese bioaktiver Naturstoffe als neuartige Wirkstoffe gegen Krebs, Bakterien und Viren, die Synthese von Alkaloiden und Peptidmimetika für die Behandlung neurodegenerativer Störungen sowie die Synthese von Peptid‐ und Glycopeptidbestandteilen für Impfstoffe gegen den schwarzen Hautkrebs. In der Angewandten Chemie hat sie die Totalsynthese von Paecilospiron vorgestellt5a und im European Journal of Organic Chemistry die Synthese 6,5‐benzanellierter Spiroketale 5b…”