Epoxides bicyclic

Epoxidation of norbornene was found some time prior to this work not to stop at the monoepoxide step. Instead, this intermediate goes on to rearrange to the bicyclic aldehyde, 31, ... 

Steps 1-2 of Figure 27.14 Epoxide Opening and Initial Cyclizations Cyclization is initiated in step 1 by protonation of the epoxide ring by an aspartic acid residue in the enzyme. Nucleophilic opening of the protonated epoxide by the nearby 5,10 double bond (steroid numbering Section 27.6) then yields a tertiary carbo-cation at CIO. Further addition of CIO to the 8,9 double bond in step 2 next gives a bicyclic tertiary cation at C8. 

The hydrogeh atom bound to the amide nitrogen in 15 is rather acidic and it can be easily removed as a proton in the presence of some competent base. Naturally, such an event would afford a delocalized anion, a nucleophilic species, which could attack the proximal epoxide at position 16 in an intramolecular fashion to give the desired azabicyclo[3.2.1]octanol framework. In the event, when a solution of 15 in benzene is treated with sodium hydride at 100 °C, the processes just outlined do in fact take place and intermediate 14 is obtained after hydrolytic cleavage of the trifluoroacetyl group with potassium hydroxide. The formation of azabi-cyclo[3.2.1]octanol 14 in an overall yield of 43% from enone 16 underscores the efficiency of Overman s route to this heavily functionalized bicycle. 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

Aziridinocyclopropanes 163 derived from 2-phenylsulfonyl-l,3-dienes undergo BF3-induced rearrangement to bicyclic amines 165, which feature the skeleton of the tropane alkaloids. The reaction proceeds via cyclopropyl carbinyl cation 164, an intermediate also invoked in the analogous epoxide rearrangements. Trapping by fluoride ion is a competing pathway <96TL3371>. 

Scheme 10.1 gives some representative examples of laboratory syntheses involving polyene cyclization. The cyclization in Entry 1 is done in anhydrous formic acid and involves the formation of a symmetric tertiary allylic carbocation. The cyclization forms a six-membered ring by attack at the terminal carbon of the vinyl group. The bicyclic cation is captured as the formate ester. Entry 2 also involves initiation by a symmetric allylic cation. In this case, the triene unit cyclizes to a tricyclic ring system. Entry 3 results in the formation of the steroidal skeleton with termination by capture of the alkynyl group and formation of a ketone. The cyclization in Entry 4 is initiated by epoxide opening. 

Another epoxidation, followed by fragmentation gave the bicyclic intermediate that contains the eight-membered ring and bridgehead double bond properly positioned for conversion to Taxol (Steps B-2 and B-3). 

The following syntheses of five-membered carbocyclic systems involve radical-induced epoxide fragmentation with radical translocation and cyclization. The resulting bicyclic alcohols are formed as a mixture of two epimeric esters with cw-fused rings.[71]... 

The reductive demercuration was marred by the loss of about half of the peroxide due to competing deoxymercuration which afforded 4-cycloocten-l-ol. An additional complication was the formation of a small amount of trans-1,2-epoxy-cw-cyclooct-5-ene. The bicyclic peroxide 50 was readily separated from the unsaturated alcohol by silica chromatography, but complete removal of the epoxide was more difficult. Preservation of the peroxide linkage was markedly higher in the bromodemercuration. The diastereoisomeric dibromoperoxides 51 were separated by HPLC, although only one isomer was fully characterised. 

A rather new concept in the context of domino radical cydizations has been developed by Gansauer and coworkers utilizing titanocene-complexes for the radical opening of unsaturated epoxides. The titanocene-catalyzed reactions [61] of 3-145 primarily led to radical 3-146, which underwent a subsequent intermolecular addition to a present a,(3-unsaturated carbonyl compound to form bicyclic carbocy-cles of type 3-148 via the intermediate 3-147 after aqueous work-up (Scheme 3.38) [62]. From a kinetic point of view, the reaction is remarkable since the intermolecular addition of simple radicals to a,(3-unsaturated carbonyl compounds is not an easy task, as highlighted above. 

Pyran-4-ones bear an obvious structural similarity to the all-carbon cyclohexadienones discussed above. However, the original studies of their photochemical behavior revealed only dimerization processes to produce a cage product resulting from two successive head-to-tail [2 + 2]-photocycloadditions (Scheme 29)54. Much later, small amounts of substituted furfural 121 were observed during the irradiation of 11955a. It was speculated that 121 could arise from bicyclic epoxide 120, an intermediate analogous to those formed in cyclohexadienone photochemistry. Subsequent reports noted that further irradiation of... 

By the same type of epoxide rearrangement, other bicyclic and tricyclic orthoesters can be synthesized [80]. However, the orthoesters are only the kinetic products and, if not sufficiently inert, can further rearrange under reaction conditions to more stable tetra-hydrofuran derivatives (cf. Scheme 8.40). In many cases, the tetrahydrofurans are the... 

An unusual rearrangement has been observed when fra r-a,/3-unsaturated ester 260 on treatment with MCPBA gave a mixture of three products in 80% yield. The most abundant product was identified as the bicyclic 7-lactam 261 (45%) and the minor constituents were identified as the epoxides 262 (19%) and 263 (17%) (Equation 40) <2003T241>. A mechanism has been postulated to explain this transformation (Scheme 39). 

Hsung and co-workers described the first epoxidation of 1-amidoallenes leading to highly reactive intermediate 292 (Scheme 8.76) [159]. Formation of bicyclic products 291 occurs via iminium enolate 293, which was trapped by cyclopentadiene 290 (X = CH2) or furan 290 (X = 0). [4+3] Cycloaddition of the intermediate 293furnished 291 in good yield as a mixture of mdo-diastereoisomers (-75 25). The best dia-stereoselectivity was found when the reaction was performed in the presence of 2 equiv. of zinc chloride (>96 4). 

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