Tandem cyclisations involving α-ketenyl alkyl radicals. New syntheses of the natural triquinanes pentalenene and modhephene

Abstract

New synthetic approaches to the angular and propellane sesquiterpene triquinanes (+/-)-pentalenene 2 and (+/-)-modhephene 3, respectively, are described. The syntheses are based on tandem cyclisations involving alpha-ketene alkyl radical intermediates produced from alpha,beta-unsaturated acyl radical species, as highlighted in Schemes 2 and 4.

Occurrence, synthesis and applications of natural and designed [3.3.3]propellanes

“…Radical cyclizations constitute another popular approach to the construction of the [3.3.3]propellane cores, either via an intramolecular radical cyclization from a cyclopentane or diquinane core bearing appropriate side chains 60,84,[94][95][96][97][98][99][100][101][102] or by means of a domino transannular radical cyclization of a substituted cyclooctane derivative. [103][104][105] 3.5.1 Curran and co-workers. In 1990, Curran and Jasperse developed a synthesis of the natural product (AE)-modhephene ((AE)-1) based on a series of radical cyclizations.…”

“…101 3.5.8 Pattenden and co-workers. Pattenden and co-workers also proposed a formal synthesis of (AE)-modhephene ((AE)-1) based on the domino transannular radical cyclization of a cyclooctenyl substituted a-ketenyl radical 205, 104,105 itself generated by heating thioester 203 in presence of Bu 3 SnH and AIBN, as depicted in Scheme 28. This strategy allowed them to report a synthesis of [3.3.3]propellane 204, which is a precursor of (AE)-modhephene ((AE)-1).…”

Treasures old and new: what we can learn regarding the macrocyclic problem from past and present efforts in natural product total synthesis

“…The Pattenden group 60 had for a number of years studied radical mediated macrocyclisation-transannulation. [61][62][63][64] Later they reported the addition of vinylic radicals to furans resulting in a cascade culminating in the tetracyclic diketone (33) (Scheme 10). It is…”

Synthesis of propellane-containing natural products

“…The latest synthesis of modhephene was published by De Boeck and Pattenden. 170,171 Their approach called for the construction of an eight-membered ring that was then cyclized by virtue of an a-ketenyl radical intermediate into propellane 209.…”