Cyclopentene oxides rearrangement

Isomerization of epoxides to allylic alcoholsThis rearrangement has been effected with strong bases and various Lewis acids. Enantioselective rearrangement to optically active allylic alcohols can be effected with catalytic amounts of vitamin B, at 25°. Thus cyclopentene oxide rearranges to (R)-2-cyclopentene-l-ol in 65% ee. The rearrangement of the as-2-butene oxide to (R)-3-butene-2-ol in 26% ee is more typical. 

Nevertheless, whereas the base-promoted isomerization of simple linear oxiranes and cyclohexene oxide occurs via a -deprotonation mechanism, recent denterinm-labeUng experiments demonstrate that the LDA-mediated rearrangement of cyclopentene oxide in nonpolar solvents furnishes the corresponding cyclopentenol through an a-deprotonation route (Scheme 7) . 

The first study was performed by Milne and Murphy, who found that the rearrangement of substituted cyclopentene oxide 69 into 70 by a stoichiometric amount of the dilithiated homochiral base 71 derived from norephedrine occurred in excellent yield and good ee... 

The catalytic asymmetric rearrangement of functionalized cyclohexene and cyclopentene oxides to give chiral allylic alcohols has been studied using sub-stoichiometric amounts of a chiral lithium amide in combination with a stoichiometric amount of different lithiated imidazoles (Scheme 47).79... 

Hodgson and coworkers used lithium amide 9 to rearrange the cyclopentene oxide 10 into the allylic alcohol (15,4/J)-11 with 95% ee (Scheme 5)12,13. The sense of asymmetric induction found in this case was opposite to that observed by Murphy. Interestingly, no allylic alcohol could be obtained with protected epoxide (TBS or benzyl) in the presence of 9. 

Chiral base 14 was also used to convert the substituted c/s-cyclopentene oxide 15 to the corresponding cyclopentenol derivative (1/ ,4S>16 in up to 90% ee using 3 equiv. of chiral base (Scheme 11). The rearrangement in presence of 3.3 equiv. of DBU gave the product in 83% ee. 

A synthetic route to Q, /i-disubstituted cycloalkenones via a four step one-pot synthesis employed (4a) for RCM and then oxidative rearrangement giving products in low to moderate overall yields as a way to access estrogen receptor ligand tetrahydrofluorenones (equation 29)3 Crimmins reported an asymmetric aldol-oleftn metathesis approach to the synthesis of functionalized cyclopentenes exploiting the acyclic stereocontrol of the aldol reaction with efficient (2a) catalyzed RCM (equation 30)3 ... 

Aryl epoxides undergo rearrangements to aldehydes and ketones in the presence of Lewis acid catalysts. For example, the cyclopentene oxide derivative 80 opens up to the more stable benzylic carbocation, which then provides the cyclopentanone derivative 82 via 1,2-methyl migration in 93% yield <01T815>. A similar rearrangement (83 84) has been shown to... 

Evidence for the mechanism is provided by the fact that cyclopentene oxide (36) does not react , as its rearrangement would require the existence of the intermediate 37 which possesses two rro/u-fused five-membered rings. The thiiran 38, however, reacts smoothly and gives 39. This striking difference in behaviour can probably be attributed mainly... 

Deuterium labelling studies have revealed that the lithium amide-induced desym-metrizing rearrangements of 4-substituted cyclopentene oxides to cyclopentenols generally proceed by a -elimination mechanism. Highly enantioselective syntheses of 4-substituted c -4-hydroxymethylcyclopent-2-en-l-ols are described. 

In fluorosulfonic acid the anodic oxidation of cyclohexane in the presence of different acids (RCO2H) leads to a single product with a rearranged carbon skeleton, a 1-acyl-2-methyl-1-cyclopentene (1) in 50 to 60% yield (Eq. 2) [7, 8]. Also other alkanes have been converted at a smooth platinum anode into the corresponding a,-unsaturated ketones in 42 to 71% yield (Table 1) [8, 9]. Product formation is proposed to occur by oxidation of the hydrocarbon to a carbocation (Eq. 1 and Scheme 1) that rearranges and gets deprotonated to an alkene, which subsequently reacts with an acylium cation from the carboxylic acid to afford the a-unsaturated ketone (1) (Eq. 2) [8-10]. In the absence of acetic acid, for example, in fluorosulfonic acid/sodium... 

Although cyclic azoalkanes are well known as biradical precursors [159] they have been used as 1,2- and 1,3-radical cation precursors only recently [160-164]. Apart from the rearrangement products bicyclopentane 161 and cyclopentene 163, the PET-oxidation of bicyclic azoalkane 158 yields mostly unsaturated spirocyclic products [165]. Common sensitizers are triphenyl-pyrylium tetrafluoroborate and 9,10-dicyanoanthracene with biphenyl as a cosensitizer. The ethers 164 and 165 represent trapping products of the proposed 1,2-radical cation 162. Comparison of the PET chemistry of the azoalkane 158 and the corresponding bicyclopentane 161 additionally supports the notion that the non-rearranged diazenyl radical cation 159 is involved (Scheme 31). 

The last synthesis to evolve which is due to Ito and his coworkers is interesting in that it relies on a stereospecific skeletal rearrangement of a bicyclo[2.2.2]octane system which in turn was prepared by Diels-Alder methodology (Scheme XLVIII) Heating of a toluene solution of cyclopentene 1,2-dicarboxylic anhydride and 4-methylcyclohexa-l,4-dienyl methyl ether in the presence of a catalytic quantity of p-toluenesulfonic acid afforded 589. Demethylation was followed by reduction and cyclization to sulfide 590. Desulfurization set the stage for peracid oxidation and arrival at 591. Chromatography of this intermediate on alumina induced isomerization to keto alcohol 592. Jones oxidation afforded diketone 593 which had earlier been transformed into gymnomitrol. 

Butene is oxidized to methyl ethyl ketone, presumably arizing from the acid-catalyzed rearrangement of the peroxide. Alkenols and aldehydes are formed in lower amounts. Cyclopentene is more reactive towards oxidation than butenes. 

Vinylcyclopropane - cyclopentene.2 This one-electron oxidant permits rapid rearrangement of some vinylcyclopropanes to cyclopentenes in CH3CN at ambient temperatures. 

First, following the results of the 1,6-dioxa-spiro[2.5]octane rearrangement (5,19), continuous gas phase conditions were applied in a fixed bed reactor and secondly under liquid phase conditions in a slurry reactor. The catalytic experiments carried out showed that two main reactions took place rearrangement of 18 to the aldehyde 19 and a oxidative decarbonylation reaction to the olefine 1,3,3,4-tetramethyl-cyclohex-l-ene 20, which is assumed to be caused by a formaldehyde elimination reaction. Also observed was a deoxygenation reaction to the alkane 1,1,2,5-tetra-methylcyclohexane 21 (Eq. 15.2.7), explained by elimination of CO. There are several other side-products such as 2,2,3,6-tetramethylcyclohex-l-enyl-methanol, ringcontracting compounds and double bond isomers of dimethyl-isopropylene-cyclopentene. 

Several electrochemical methods for alkane oxidation have been used by Fleisdimann and his cowork-ers. These proceed via caibonium ion intermediates and, as expected, extensive rearrangement can be observed for example, cycldiexane in FSO3H gives l-acetyl-2-methyl-l-cyclopentene as major product ... 

In 1995, Mioskowski and co-workers reported a new carbenoid 1,2-alkyl rearrangement of a-hydroxy-substituted cyclopentene and cyclohexene oxides treatment of such systems with 3 equiv of an organolithium resulted in the formation of two products, as exemplified by the synthesis of dihydrojasmone and its regioisomer 99 (Scheme 44) <1995JA12700>. 

Dinnocenzo and Conlon have described the remarkable effect of one-electron oxidation on the rate of certain vinylcyclopropane rearrangements. Exposure of several l-p-anisyl-2-vinylcyclopropane derivatives to a catalytic amount of tris(4-bromophenyl)aminium hexafluoroantimonate in acetonitrile at room temperature was found to induce ring expansion to form cyclopentenes (equation 25) temperatures in excess of 200 °C are required for the conventional thermal rearrangement cf these systems. At this time it is uncertain whether these reactions follow concerted mechanisms, or are stepwise processes involving trimethylene cation radical intermediates. 

It was shown by Ortiz de Montellano et al. that bicyclo[2.1.0]pentane was oxidized by rat liver microsomes to a 7 1 mixture of e <7o-2-hydroxy-bicyclo[2.1.0]pentane and 3-cyclopenten-l-ol, consistent with a radical ring-opening reaction. Applications of the radical-clock method by Ingold and by Newcomb began to measure the lifetime of the suspected radical cage intermediate. The rate constant for the rearrangement of bicyclo[2.1.0]pent-2-yl radical to 3-cyclopenten-... 

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