Enones electron-deficient

Avery powerful oxidant, TMDO epoxidizes alkenes up to 10 times faster than the widely used dimethyldioxirane (DMDO), which in turn reacts 10 times faster than a peracid such as perbenzoic acid. The electron-deficient enone C=C bond in anthracycline 59 resists attack by DMDO, but reacts with TMDO to give epoxide 60 in 95% isolated yield. " Naphthalene (61) is transformed by TMDO into dioxide 62... 

Benzoate salt of the vicinal diamine (249) has been found to catalyse a domino reaction of enones R CH=CHCOR with R CH=CHCOR that affords cyclic products containing three to four contiguous stereocentres (with 92-99% ee and >30 1 dr) " The self-assembly of proline and cinchona alkaloid-derived thioureas has been reported to dramatically improve the enantioselectivity of the inverse-electron-demand hetero-Diels-Alder reactions between aldehydes R R CHCH=0 and electron-deficient enones R CH=CHCOR , affording (250) after subsequent oxidation with PCC. °... 

Catalytic enantioselective nucleophilic addition of nitroalkanes to electron-deficient alke-nes is a challenging area in organic synthesis. The use of cinchona alkaloids as chiral catalysts has been studied for many years. Asymmetric induction in the Michael addition of nitroalkanes to enones has been carried out with various chiral bases. Wynberg and coworkers have used various alkaloids and their derivatives, but the enantiomeric excess (ee) is generally low (up to 20%).199 The Michael addition of methyl vinyl ketone to 2-nitrocycloalkanes catalyzed by the cinchona alkaloid cinchonine affords adducts in high yields in up to 60% ee (Eq. 4.137).200... 

The epoxidation of electron-deficient alkenes, particularly a,P-unsaturated carbonyl compounds, continues to generate much activity in the literature, and this has been the subject of a recent concise review <00CC1215>. Additional current contributions in this area include a novel epoxidation of enones via direct oxygen atom transfer from hypervalent oxido-).3-iodanes (38), a process which proceeds in fair to good yields and with complete retention of... 

The first example of asymmetric rhodium-catalyzed 1,4-addition of organoboron reagents to enones was described in 1998 by Hayashi and Miyaura. Significant progress has been made in the past few years. This asymmetric addition reaction can be carried out in aqueous solvent for a broad range of substrates, such as a,/ -unsaturated ketones, esters, amides, phosphonates, nitroalkenes. The enantioselectivity is always very high (in most cases over 90% ee). This asymmetric transformation provides the best method for the enantioselective introduction of aryl and alkenyl groups to the / -position of these electron-deficient olefins. 

In the phosphonium salt synthesis, the addition reaction of tertiary phosphines to activated alkenes has been reported (Scheme 3). PPh3 is added to electron-deficient alkenes such as enones or enals at the p-position in the presence of acids.4 The reaction of styrenes with phosphine has recently been reported by Okuma, which gave Markovnikov adducts.5 Although no catalyzed reactions of... 

Cycloadditions and cyclization reactions are among the most important synthetic applications of donor-substituted allenes, since they result in the formation of a variety of carbocyclic and heterocyclic compounds. Early investigations of Diels-Alder reactions with alkoxyallenes demonstrated that harsh reaction conditions, e.g. high pressure, high temperature or Lewis acid promotion, are often required to afford the corresponding heterocycles in only poor to moderate yield [12b, 92-94]. Although a,/3-unsaturated carbonyl compounds have not been used extensively as heterodienes, considerable success has been achieved with activated enone 146 (Eq. 8.27) or with the electron-deficient tosylimine 148 (Eq. 8.28). Both dienes reacted under... 

Asymmetric induction of the Michael addition of thiols to electron-deficient alkenes (4.6.1) has been achieved in high overall conversion using both free [e.g. 12-20] and polymer-supported [e.g. 21, 22] cinchona alkaloids and their salts [23-25], but with varying degrees of optical purity. The corresponding asymmetric Michael addition of selenophenols to cyclohex-2-enones is promoted by cinchoni-dine to give a chiral product (43% ee) [26],... 

Direct phase-transfer catalysed epoxidation of electron-deficient alkenes, such as chalcones, cycloalk-2-enones and benzoquinones with hydrogen peroxide or r-butyl peroxide under basic conditions (Section 10.7) has been extended by the use of quininium and quinidinium catalysts to produce optically active oxiranes [1 — 16] the alkaloid bases are less efficient than their salts as catalysts [e.g. 8]. In addition to N-benzylquininium chloride, the binaphthyl ephedrinium salt (16 in Scheme 12.5) and the bis-cinchonidinium system (Scheme 12.12) have been used [12, 17]. Generally, the more rigid quininium systems are more effective than the ephedrinium salts. 

Metal alkyl peroxides can be used for the epoxidation of electron-deficient alkenes such as enones. The use of a combination of diethylzinc, oxygen, and A-methylephedrine gave epoxides in very high yield and generally high enantio-selectivity (Figure 11.8). " ... 

Molander and Hiersemann (60) reported the preparation of the spirocyclic keto aziridine intermediate 302 in an approach to the total synthesis of (zb)-cephalotax-ine (304) via an intramolecular 1,3-dipolar cycloaddition of an azide with an electron-deficient alkene (Scheme 9.60). The required azide 301 was prepared by coupling the vinyl iodide 299 and the aryl zinc chloride 300 using a Pd(0) catalyst in the presence of fni-2-furylphosphine. Intramolecular 1,3-dipolar cycloaddition of the azido enone 301 in boiling xylene afforded the desired keto aziridine 302 in 76% yield. Hydroxylation of 302 according to Davis s procedure followed by oxidation with Dess-Martin periodinane delivered the compound 303, which was converted to the target molecule (i)-cephalotaxine (304). 

Nnmerons other protocols have been developed to prepare magnesium enolates by asymmetric 1,4-addition of Grignard reagents to electron-deficient alkenes. Recently, an enantioselective metal-catalyzed version of this key reaction has been studied with enones and a, S-unsaturated thioesters Using chiral ferrocenyl-based diphosphines leads to... 

The epoxidation of electron-deficient alkenes with either vanadium or titanium catalysts give syw-epoxides347 a free hydroxy group and a ketone or ester function are necessary for the reaction to take place, and a modest level of asymmetric induction can be achieved with y-hydroxy enone substrates and chiral titanium catalysts348. 

Reductive arylation of enones, TiCl3 induces homolytic dediazotization of diazonium salts to produce aryl radicals, which arylate electron-deficient alkenes.1 Example ... 

The normally sluggish Diels-Alder cycloaddition between cyclohexa-1,3-diene and various enones and enals can be activated by precoordination of the diene to a jt-basic molybdenum complex TpMo(NO)MeIm(//-cyclohexadiene)].134 The 4-1-2-cycloaddition of cyclohexa-2,4-dienones with electron-deficient 2n -dienophiles produced bridged bicyclo[2.2.2]octenones. Triplet-sensitized irradiation of these bridged bicyclooctenones produced bicyclo[3.3.0]octanoids, whereas direct irradiation yielded bicyclo[4.2.0]octanes.135... 

Electron-deficient alkenes, either these with conjugating substituents or of enones, undergo Michael-like additions with regiospecific introductions of the nucleophiles, and this approach has been successful for the formation of cyclopropyl derivatives—notably from some nucleosides. An example involves the addition of the anion of bis(phenylsulfonyl)methane to the phenylselenone 173 which gives the adduct 174 in 35% yield. This reaction presumably occurs by Michael addition to C-2 followed by Sn2 ring-closure reaction at C-3 with displacement of phenylselenic acid. Reductive desulfonylation affords the 2,3,-dideoxy-2,3 -cyclopropayuridine 175.199... 

A new iodine-catalysed, remarkably simple Michael reaction of indoles with enones, e.g. PhCH=CHCOR, has been developed.183 The Sml3-catalysed reaction of indoles with electron-deficient alkenes (e.g. enones) afforded the corresponding Michael adducts in high yields. As in the previous case, the substitution on the indole nucleus occurred exclusively at the 3-position and A-alkylation products have not been observed.184... 

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