2Ј-Alkoxytricyclo[3.2.1.0 2,7
]octanes 4-R are obtained in good give chelation-stabilized cyclopropyllithium derivatives 6-Me, which react with electrophiles to yield the 7Ј-substituted to excellent yields from methyl 2-chloro-2-cyclopropylideneacetate (3) and the dienolates derived from the 3-alkoxycyc-tricyclo[3.2.1.0 2,7 ]octanes 4f؊i-Me (61Ϫ66%). By acidic workup of such reaction mixtures, or subsequent treatment lohex-2-enones 1-R and 2-R, by a cascade of two consecutive Michael additions and a γ-elimination. Compounds 4-R are of the isolated products 4f؊i-Me with acid, efficient transformation to the correspondingly substituted bicyclo[3.2.1]octa-transformed to the correspondingly substituted bicyclo-[3.2.1]octanecarboxylates 5 by treatment with acid. 2Ј-Meth-necarboxylates 5 is observed. oxytricyclooctanes 4a؊d-Me are readily deprotonated to
The bicyclo[3.2.1]octane ring system is a key structural by alkylation of the dienolates from 1a-Me and 1c-Bu with, respectively, methyl iodide and allyl bromide. component in a large variety of tri-and tetracyclic sesquiand diterpenes and their metabolites. [2] The basic skeleton Enone 2-Bzl was prepared by C-allylation of cyclohexane-1,3-dione and subsequent O-benzylation, demonstrat-has frequently been constructed by intramolecular alkylation, [3] ring expansion, [4] and aldol reaction. [5] The facile ing an option for additional functionalization of the tricyclo[3.2.1.0 2,7 ]octanes 4-R at C-5Ј and C-7Ј. Treatment of the formation of tricyclo[3.2.1.0 2,7 ]octane derivatives upon cascade cycloaddition [6] of methyl 2-chloro-2-cyclopropyli-tricyclic γ-oxo esters 4-R with an acid (HCl, CF 3 COOH, p-TsOH) in dichloromethane afforded the 2Ј,6Ј-dioxobicy-deneacetate (3), which is readily available in three steps from ethylene and tetrachlorocyclopropene, [7] with cyclo-clo[3.2.1]octanecarboxylates 5 in excellent yields (51Ϫ98%).
Moreover, this two-step process, consisting of a cascade of hexa-1,3-dienolates Li-1R, prompted us to investigate such compounds further and to look at their subsequent trans-two consecutive Michael additions followed by γ-elimination, and then subsequent retrograde aldol reaction under formations to highly functionalized bicyclic skeletons. The 2Ј-alkoxy-substituted derivatives 4 are of particular interest, acidic hydrolytic conditions, could easily be carried out in one pot. as they contain a vicinally "push-pull"-type substituted cyclopropane unit, [8] and can therefore undergo an acid-Kinetic Acidity of the Tricyclic Oxo Ester 4-R and the catalyzed retro-aldol reaction to give functionalized bi-Reaction of 6-Me with Electrophiles cyclo[3.2.1]octane derivatives 5, some of which appear to be potential precursors to spirocyclopropane analogues of Deprotonation of the tricyclic γ-oxo ester 4-Me with LDA in THF occurred only at C-7Ј. This could be shown terpenoid natural products.
by the constitution of the isolated products after quenching A number of lithium cyclohexadienolates Li-1-R, generof 6-Me with electrophiles. Thus, alkylation and silylation ated from the corresponding 3-alkoxycyclohex-2-enones 1with methyl iodide and chlorotrimethylsilane gave 4f-Me R with lithium diisopropylamide (LDA), reacted with the and 4g-Me, in 61% and 66% yield, respectively. α-chloroacrylate 3 to give the tricyclic γ-oxo esters 4-R in It is quite remarkable, since it cannot lead to a regularly good yields. [9] The enones, 1b-Me and 1d-Bu, were obtained stabilized enolate, [10] that the tricyclic γ-oxo ester 4c-Me is so easily deprotonated, even though the carbonyl group at [᭛] Part 37: Ref. [1] .