Cyclic epoxy ketone

The condensation of o-aminothiophenol and epoxy-ketones of type (13) yields benzothiazolines (14). Cyclic epoxy-ketones form the spirans (15) analogously. ... 

The rt,/3-unsaturated linear carbonyl compound 39 is obtained by the decomposition of the cyclic hydroperoxide 38 with PdCl2,[35]. The a, 0-epoxy ketone 40 is isomerized to the /3-diketone 41 with Pd(0) catalyst[36]. The 1,4-epiperoxide 42 is converted into the /3-hydroxy ketone 43 and other products[37]. 

Interestingly, we were intrigued by the ESI mass spectrum of the compound, as the observed base peak consisted of [M-S02+Na]+. This led us to explore a thermal retro-Diels-Alder reaction that could afford the desired enone 69. It is noteworthy that the chemistry of cyclic enol-sulfites would appear to be an under-explored area with a few references reporting their isolation being found [57]. At last, we were also able to prepare epoxy ketone 70 from 69 in three steps, albeit epoxidation did not take place unless the TES group was removed. Spartan models reaffirmed our initial conformational assessment of enone 69 and epoxy ketone 70, which contain sp3-hybridized C8a and s/r-hybridized C8b (p s e u d o-. v/r - h y b r i d i zed C8b for 70) at the AB-ring junction (Fig. 8.12) and displayed the desired twisted-boat conformation in A-ring. 

The cyclic a-chloro ketone 81 which forms the (Z)-enolate only also underwent the asymmetric Darzens condensation with various aldehydes by use of the Merck catalyst 7 (R=4-CF3, X=Br) under analogous conditions to furnish the a,(3-epoxy ketones 82 with up to 86 % ee,160611 as shown in Scheme 25. It should be noted that this high enantioselectivity was attained by the reaction at room temperature. 

Replacing the electrophilic epoxy ketone moiety in TPX by a reversible zinc chelator such as a hydroxamic acid was carried out by Yoshida et al. (Fig. 6) [51]. This modification led to a low nanomolar reversible inhibitor of the HDACl enzyme. Several other cyclic tetrapeptides containing the epoxyketone feature, such as chlamydocin, were converted into their hydroxamic acid coimterparts as well [52]. Additionally, the introduction of reversed hydroxamic acids (-N(OH)COR, with R = H or Me) onto the structure of Cyl-1 was reported to give potent HDAC inhibitors as illustrated in Fig. 6 [53]. Generally, the most potent inhibitors were the examples with R = H and m = 2. Apicidin, a cychc peptide more remotely related to TPX, exhibits potent antiprotozoal activity via HDAC inhibition in parasites [54]. 

The spiroannulation of cyclic a-epoxy ketones proceeded stereospecifically, but with acyclic a-epoxy ketones the stereospecificity was lost during the oxaspiropentane-forming step, e.g. formation of cyclic a-epoxy ketones 11a, b and acyclic a-epoxy ketones 12/12. 69... 

Cyclic a,p-unsaturated ketones370 can be cleaved by treatment with base of their epoxy tosylhydrazone derivatives to give acetylenic ketones.371 The reaction can be applied to the formation of acetylenic aldehydes (R = H) by using the corresponding, 2,4-dinitrotosylhy-drazone derivatives.372 Hydrazones (e.g., 47) prepared from epoxy ketones and ring-sub-... 

Iy2-Acyl rearrangement of a, -epoxy ketones. This rearrangement can be used for synthesis of cyclic spiro-1,3-ketones. Thus the 2-cycloheptylidenecyclopenta-none oxide 1 rearranges in the presence of BF3 etherate at 25° within one minute to the spiro-1,3-diketone 2 in 91% yield.1... 

The reduction of a, (3-epoxy ketones using Sml2 is also possible. A range of acyclic and cyclic epoxides with different substitution patterns underwent reduction to give the desired aldol products in good yields (Scheme 4.26).31... 

Mai and co-workers have reported that the deoxygenation of cyclic a,/3-epoxy ketones (and acyclic a,/3-epoxy esters) is accomplished in high yields under mild and neutral conditions by the use of Mo(CO)6 (Table 14) <2003TL2355>. 

A special reaction type involves the a,p-epoxy ketone to alkynone fragmentation, often cited as the Eschenmoser fragmentation . First published by Eschenmoser, and a little later and independently by Tanabe, the utility of this fragmentation for the synthesis of open-chained or cyclic alkynones (Scheme 3) is obvious. 

Reaction with epoxides and cyclic sulfates. Opening of epoxides affords iodo-hydrins. Epoxy ketones are converted to a-iodo enones. Cyclic sulfates give alkenes. ... 

Dihydroxy allenes are generated from ketoenes and ethynyl epoxides. a,P-Epoxy ketones undergo reductive cleavage but the P-hydroxy ketones thus obtained can react further, for example with an e, -double bond to give cyclic 1,3-diols. Note that the double bond does not have to be activated, and furthermore, a silylalkyne moiety and a tricarbonylchromium-complexed arene can play the same role, although in the latter case the net result is a cine-substitution. 

Photoreduction of a,P-epoxy ketones is possible in the presence of an external and efficient hydrogen donor such as triethylamine. An application in carbohydrate chemistry is described by J. Cossy. In the final step of a 7-step synthesis, a cyclic a,P-epoxy ketone is reduced (with retention of configuration) to a P-hydroxy ketone. 

Reactions of free ketones with imines are far more restricted than those with preformed iminium salts. Examples of ketone-imine condensations are included in several reviews - and are limited to the use of arylimines, mainly benzylideneaniline. Blatt and Gross have noted that the reproducibility of uncatalyzed additions of ketones to Schiff bases is poor but can be improved by the addition of small amounts of hydrochloric acid. The highest yields of 3-amino ketones are obtained using 10 mol % of concentrated hydrochloric acid and 95% ethanol as solvent, and by performing the reaction at room temperature. The reaction, however, is of limited applicability, as it is restricted to methyl ketones and cycloalkanones. Deamination leading to unsaturated ketones is a major side reaction. In addition to hydrochloric acid, boron trifluoride etherate has been used as a catalyst in reactions of aromatic imines with methyl ketones, cyclic ketones and an epoxy ketone. ... 

Formation of spiro orthoesters such as 4 is achieved in high yield by reaction of cyclic ketene monothioacetals such as 3 with ethanediol and camphorsulfonic acid <04SL2013>. A variety of substituted epoxy ketones 5 rearrange to the benzodioxoles 6 upon treatment with Bu.,N CN in CHjClj or K1 in acetone <04T3825>. Condensation of phenacyl carbonates 7 with aromatic aldehydes in the presence of MgCClO ), 2,2 -bipyridyl, A-methylmorpholine and molecular sieves gives the trans dioxolanones 8 <04SL1195>. 

Vilsmeier reactions on 1,3-diketones, 1,4-diketones, and conjugated enones give cyclic products as shown by the reactions of compounds 86 (Eq. 81), 87 (Eq. 82), and 88 (Eq. 83). The reaction of the Vilsmeier reagent with a,jS-epoxy ketones also gives benzaldehydes or 1,3-phthalaldehydes (Eq. 83a) ... 

Hydroxy-3-alkylcyclopent-2-ene-l-ones. The substances (2) are available in 50-70% yield by treatment of 2,3-epoxy-2-alkylcyclopentanones (1, obtained by alkaline epoxidation of 2-alkylcyclopent-2-ene-l-ones) with acetic acid containing 2% of concentrated sulfuric acid at 55°. Use of boron trifluoride etherate, the classical reagent for rearrangement of cyclic 2,3-epoxy ketones (1,... 

Both open chain and cyclic epoxy alcohols can be neatly transformed into the corresponding epoxy ketones with high conversions and yields using just 1.1-1.5 equiv of DDO oxidant. Also, the conversion of optically active epoxy alcohols into epoxy ketones occurs selectively leaving the configuration at the chiral center(s) at the oxirane ring unaffected. ... 

Fused 2-methylbutenolides have been prepared in good yield by the addition of 1-diethylaminopropyne to cyclic a-epoxy-ketones (Scheme 21). The intermediate unsaturated amide can by cyclized to the hydroxy derivatives (69) simply by treatment with acid. Alternatively, prior reaction with BF3 followed by acid leads to the unsaturated analogue (70), whereas final reduction with borohydride gives the... 

NAP-MgO acts as a bifunctional heterogeneous catalyst for the Claisen-Schmidt condensation (CSC) of benzaldehydes with acetophenones to yield chalcones, followed by asymmetric epoxidation (AE) to afford chiral epoxy ketones in moderate to good yields and impressive enantioselectivities (ee s). NAP-MgO, in combination with the chiral auxiliary (11 ,21 )-(- -)-1,2-diphenyl-1,2-ethylenediamine (DPED), catalyzed the asymmetric Michael addition of malonates to cyclic and acyclic enones. 

Irradiation of 2,5-dimethylbenzoyl oxiranes results in formation of p-hydroxy functionalized indanones (74) that structurally resemble biologically active pterosines. Nanosecond laser flash photolysis and quantum-chemical calculations based on density functional theory support a photoenolization mechanism.Reversible photochemical transformations of cis- and tra v-2,3-dimethyloxirane radical cations in freonic matrices at 77 K has been observed and explained by the interconversion between the open (C2-C3 broken) and the cyclic forms. Photocatalytic ring opening of a-epoxy ketones in cyclopentanone, using 2,4,6-triphenylpyrylium tetra-fluoroborate as electron acceptor, results in the diastereoselective formation of 2,5-dioxaspiro[4,4]nonanes through Ca-O bond cleavage and subsequent nucleophilic attack by cyclopentanone to the radical cation intermediates. ... 

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