Enone derivatives

The intramolecular reductive aldol reaction of keto-enones was successfully conducted under conditions similar to those described above, employing a cationic Rh complex and PI13P (Scheme 20) [34]. The keto-enone 63 was cyclized in the presence of added K2CO3 to give the ketone-aldol 64 in 72% yield with exclusive ds-selectivity. Dione-enone derivatives, for example 68 and 70, were efficiently cyclized to furnish bicyclic aldol products 69 and 71, respectively, wherein three stereogenic centers of the bicyclic product form stereoselectivity through the intermediacy of a Rh-enolate. 

The Nazarov cyclization of vinyl aryl ketones involves a disruption of the aromaticity, and therefore, the activation barrier is significantly higher than that of the divinyl ketones. Not surprisingly, the Lewis acid-catalyzed protocols [30] resulted only in decomposition to the enone derived from 46,47, and CO. Pleasingly, however, photolysis [31] readily delivered the desired annulation product 48 in 60 % yield. The photo-Nazarov cyclization reaction of aryl vinyl ketones was first reported by Smith and Agosta. Subsequent mechanistic studies by Leitich and Schaffner revealed the reaction mechanism to be a thermal electrocyclization induced by photolytic enone isomerization. The mildness of these reaction conditions and the selective activation of the enone functional group were key to the success of this reaction. 

It was also shown that for some other related 4-substituted cyclopent-2-enone derivatives the regiofacial selectivity is lower, and completely reversed in the case of 4-acetoxycyclopent-2-enone, giving 100% of the adduct 77. 

Nazarov cyclizations of methoxymethoxylallene deliver a-methylenecyclopent-2-enone derivatives 105-107 [49, 50]. 

A chiral enone derived from carbohydrates, 131, undergoes a stereoselective [3+2] cycloaddition reaction with azomethine ylides to afford pyranopyrrolidines in good yields. The cycloaddition reaction is highly regio- and stereoselective (Equation 64) <2005SL587>. 

The reaction between acetophenone and acetic anhydride alone yields 2-methyl-4,6-diphenylpyrylium (23CB1012). It seems possible that a 1,3-diketone is formed by the acetylation of acetophenone (540R(8)59), which subsequently reacts with unchanged ketone. Alternatively, an intermediate enone derived from the condensation of two moles of acetophenone (53JA626) may be acylated to the pyrylium salt. There is supporting evidence for both reaction schemes and it is not possible to discard either alternative (Scheme 255). 

Acidic media favor the hydrolysis, and alkaline reagents, usually, but not without exceptions,141 142 do not attack geminal difluorides. Thus, perfluorocyclobutene with potassium hydroxide gives trifluoro-3-hydroxycyclobut-2-enone derivative 3.142... 

In the first attempts to use a chiral a-sulfinyi ester enolate as donor in Michael additions to a -un-saturated esters, only low selectivities were observed.185 186 Better results are obtained when the a-lithio sulfoxide (174), a chiral acyl anion equivalent, is employed. Conjugate addition of (174) to cyclopent-enone derivatives occurs with reasonably high degrees of asymmetric induction, as exemplified by the preparation of the 11-deoxy prostanoid (175 Scheme 63).187 188 Chiral oxosulfonium ylides and chiral li-thiosulfoximines can be used for the preparation of optically active cyclopropane derivatives (up to 49% ee) from a, -unsaturated carbonyl compounds.189... 

Conjugate additions of various organocopper reagents to the enones derived from glycals, e.g. 2-(diethoxyphosphoryl)hex-l-en-3-uloses, has been described. The reactions proved to be rapid, clean, and diastereoselective, giving rise to the formation of 3-oxo-2-phosphono-o -C-glycosides or the corresponding enol acetates.215... 

Chemistry of ketone dilithio dianions TABLE 5. Reaction of dianionic zincates with enone derivatives... 

In a variant of the Hantzsch synthesis N-substituted enaminones gave aminocyclohex-enone derivatives, which were convertible with Mn02 to the corresponding substituted diphenyls (see Section II.A.l.e and see equation 63). For an aromatic product resulting from cycloaddition, see Section II.A.4 (equation 144). 

Irradiation of host-guest crystals of the 2-[N-(2-propenyl) amino] cyclohex 2-enone derivatives 36 with chiral hosts 6a-c caused intramolecular [2 + 2]... 

It has not b estaUished whether enone-derived enolates are oxidized by LTA (c/. Section 2.3.2.1.2.iv), but the success of such a process seems likely. 

The original approach was designed to emulate the successful cyclization of anion V to the sativene precursor VI, by means of base treatment of a closely related enone derivative. The resulting anion (Vila) from the enone, however, failed to cyclize as predicted, yielding only the cyclopropane derivative I (see Scheme 6.2). The end result was, nevertheless, equally rewarding, since structure III exactly filled the purpose for which anion Vllb was intended. 

Mariano and coworkers have investigated the DCA sensitized photocyclization of silylamino-enone derivatives (Scheme 61) [130, 131, 308]. DCA-sensitized photoreactions of 255 in acetonitrile-methanol mixture gave the substituted piperidines 256 in high yields along with the pyrrolidine ester 257 in the case of 255b. DCA sensitized reaction of 246 resulted in the formation of a diastereomeric mixture (6 1) of hydrosoquinolines [212, 213] and <2 % of the hydrosoindoline, 258. 

Stork and Danheiser have developed a highly useful procedure for the synthesis of 4-alkylcyclohex-2-enones, which involves a -alkylations of cross-conjugated lithium dienolates of 3-alkoxycyclohex-2-enones, followed by metal hydride reduction of the carbonyl group and hydrolysis (Scheme 30). Numerous applications of this procedure have been reported.Two different alkyl groups may be introduced at the 6-position of a cyclohex-2-enone derivative without difficulty. While dialkylation is generally not a problem in alkylations of cross-conjugated dienolates of cyclohex-2-enones, it was observed when relatively acidic 3-chlorocyclohex-2-enones were employed. ... 

Murray s and Singh s studies on dialkylalkynes and alkyltrimethylsilyl-substituted alkynes likewise lead to products arising from oxirene and oxocarbene intermediates. The latter serve as precursors of products arising from hydrogen- or CH3-shifts, as well as cyclopropane insertion in some cases (Scheme 73). The enones derived from some of these carbene reactions are partially converted to 2,3-epoxyketones <93JOC5076>. 

The intramolecular cycloaddition of the enone derivative (78) affords the adducts (79) in yields of around 58%. The advantage of this compound for synthetic purposes is that the alcohol group is functionalized by a novel protecting group. The adducts (79) can be converted into derivatives such as (80). Four intramolecular cycloaddition products (82) and (83) are formed on irradiation of the naphthalenone derivative (81)." ° Changes in the regiochemistry are observed when the irradiations are carried out on silica surfaces. 

It must be emphasized that irradiation of such fused cross-conjugated cyclohexa-2,5-dienones in protic solvents such as glacial and aqueous acetic acid provided, by a different pathway, spirohydroxy enone derivatives." ... 

The use of optimized substrates and procedures allows for relatively high yields of bicyclic products to be obtained from such cycloisomerizations. For example, the enone derivative 20, which on cyclization benefits from the Thorpe — Ingold effect arising from the geminal... 

In a similar manner 1,3-di-ferf-butyl-2-phenylcyclopropenc (4) gave both di- ert-buty 1- and tert-butyl(phenyl)acetylenes, as well as an enone derived from the normal epoxidation of the cyclo-propene double bond. The mechanism by which the alkynes are formed is not clear, although radical scavengers did not significantly affect the reaction and addition of acetate did not lead to this being incorporated. 

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