Construction of the 1,2-Dialkenylcyclohexane Framework via Ireland-Claisen Rearrangement and Intramolecular Barbier Reaction: Application to the Synthesis of (±)-Geijerone and a Diastereoisomeric Mixture with Its 5-Epimer

Abstract

Abstract:The elemene-type terpenoids, which possess various biological activities, contain a syn-or anti-1,2-dialkenylcyclohexane framework. An efficient synthetic route to the syn-and anti-1,2-dialkenylcyclohexane core and its application in the synthesis of (±)-geijerone and its diastereomer is reported. Construction of the syn-and anti-1,2-dialkenyl moiety was achieved via Ireland-Claisen rearrangement of the (E)-allylic ester, and the cyclohexanone moiety was derived from the iodoaldehyde via intramolecular Barbier reaction. The synthetic strategy allows rapid access to various epimers and analogues of elemene-type products.

Enantioselektive Totalsynthese der Terreumole A und C aus dem Pilz Tricholoma terreum

“…Ein unerwartetes Problem trat bei der Hydroxyalkylierung von 12 mit dem α,β‐ungesättigten Aldehyd 13 auf. Nach Brom/Lithium‐Austausch ( t BuLi, Et 2 O) und Reaktion mit 13 isolierten wir nur den invertierten tertiären Allylalkohol 14 (72 %), der in CDCl 3 eine Eliminierung zum Dien 15 und anderen Produkten einging.…”

Copper-Catalyzed Reductive Ireland–Claisen Rearrangements of Propargylic Acrylates and Allylic Allenoates

“…To synthesize geijerone, Ireland-Claisen product 39 was obtained from 38 with a 2:1 diastereoselectivity at best. The addition of Lewis acids, which had been reported to be effective to increase both the yield and selectivity of the Ireland–Claisen rearrangement, led to a lower dr in this case …”

“…The addition of Lewis acids, which had been reported to be effective to increase both the yield and selectivity of the Ireland−Claisen rearrangement, led to a lower dr in this case. 63 One outstanding example for a successful rearrangement was reported by Fukuyama. 60 The low temperature silylation and rearrangement of β,γ-unsaturated 40 successfully delivered 41 in good yield and excellent diastereoselectivity, through the intermediacy of an (E)-enolsilane.…”

Enantioselective Total Synthesis of Terreumols A and C from the Mushroom Tricholoma terreum

“…An unexpected problem occurred in the hydroxyalkylation of 12 with α,β‐unsaturated aldehyde 13 , which was prepared in 6 steps from geraniol . After bromine/lithium exchange ( t BuLi, Et 2 O) and reaction with aldehyde 13 , we isolated the inverted tertiary allylic alcohol 14 (72 % yield), which in CDCl 3 underwent elimination to diene 15 and other products.…”

“…[10] After bromine/lithium exchange (tBuLi, Et 2 O) and reaction with aldehyde 13,w e isolated the inverted tertiary allylic alcohol 14 (72 %y ield), which in CDCl 3 underwent elimination to diene 15 and other products.Conversion to the required epoxy ketone moiety of the terreumols seemed impossible.T herefore,w et urned to RCM.…”