Chalcone-type enones

An alternative method for the epoxidation of enones was developed by Jackson and coworkers in 1997 , who utilized metal peroxides that are modified by chiral ligands such as diethyl tartrate (DET), (5,5)-diphenylethanediol, (—)-ephedrine, ( )-N-methylephedrine and various simple chiral alcohols. The best results were achieved with DET as chiral inductor in toluene. In the stoichiometric version, DET and lithium tert-butyl peroxide, which was generated in situ from TBHP and n-butyllithium, were used as catalyst for the epoxidation of enones. Use of 1.1 equivalent of (-l-)-DET in toluene as solvent afforded (2/f,35 )-chalcone epoxide in 71-75% yield and 62% ee. In the substo-ichiometric method n-butyllithium was replaced by dibutylmagnesium. With this system (10 mol% Bu2Mg and 11 mol% DET), a variety of chalcone-type enones could be oxidized in moderate to good yields (36-61%) and high asymmetric induction (81-94%), giving exactly the other enantiomeric epoxide than obtained with the stoichiometric system (equation 37). 

Quite recently, one of the most efficient phase-transfer-catalyzed epoxidation methods for chalcone-type enones was developed by the Park-Jew group [11], A series of meta-dimeric cinchona PTCs with modified phenyl linkers were prepared. Among this series, the 2-fluoro substituted catalyst 5, exhibited unprecedented activity and enantioselectivity for the epoxidation of various trans-chalcones in the... 

The conjugate hydrocyanation of rather unreactive chalcone-type enones RCH=CHCOAr, employing benzophenone cyanohydrin Ph2C(CN)OH as a precursor of HCN, and catalysed by the sodium salt generated in situ from NaNH2 and the... 

The first report of the reaction of 2//-l-benzopyran (139) with various 1,3-dipoles has appeared/ Good yields of single cycloaddition products (140) were obtained upon reaction with nitrile-imines, whereas nitrile oxides gave 1 1 mixtures of the regioisomers (141) and (142), The reactions with diazomethane gave rather inconclusive results, and phenyl azide and diphenyl nitrone failed to react. Similar types of reactions have been carried out using a variety of enones in which the overall conclusion appears to be that simple aliphatic or alicyclic enones produce mixtures of regioisomers upon reaction with nitrile oxides and nitrile imines whereas enones of the chalcone type show only one product. Experts in FMO theory will probably declare these results... 

Molecular orbital theory also predicts that a nucleophile of the sulfide type will bond at the carbon terminus of a conjugated ene carbonyl system that is, the nucleophile will bond with the electrophile in the Michael addition mode of reaction (20). Thus, the reaction of polysulfide dianion with an enone represented by a chalcone may proceed initially in such a manner as shown in Scheme 2, which reproduces one of the several pathways... 

Asymmetric -methylation of a, -enones. Chiral bidendate ligands derived from L-prolinol can be used for asymmetric Michael additions to a, 3-enones with cuprates of the type CH,L CuMgBr (10, 266). The highest optical yield in conjugate addition to chalcone is observed when L is (S)-N-methylprolinol (88% ee). The tridentate chiral ligand 1 is equally effective for asymmetric 3-methylation of chalcone with CH,L CuLi and CuBr the chemical yield is 95%. Reduction of the amide carbonyl group of 1 results in practically total loss of chiral induction. 

As described in Sections 2.3.1.2 and 2.2.3, Choudary et al. recently revealed nanocrystalline magnesium oxide (NAP-MgO) as a recyclable heterogeneous catalyst [40, 45]. These authors extended the use of this new type of heterogeneous catalyst for the asymmetric Michael reaction of different acyclic enones with nitromethane and 2-nitropropane [69a]. In a Michael reaction of chalcone with nitromethane in THF solvent at -20°C, NAP-MgO/(lR,2R)-(-)-diaminocyclohexane (DAC) was found to be an excellent catalyst system (96% ee, 95% yield) (Scheme 2.32). This Michael reaction proceeds via the dual activation of both substrates (nucleophiles and electrophiles) by NAP-MgO. The Lewis basic site (O /O ) of the NAP-MgO activates the nitroalkanes, while the Lewis acid moiety (Mg /Mg )... 

Substrates with electron acceptors are given in Scheme 4. For these rather unreactive n-systems, besides longer reaction times and excess dioxirane, elevated temperature (ca. 25 °C) was essential for complete conversion into their corresponding epoxides. Fortunately, these epoxides, which were all obtained quantitatively, were sufficiently stable for rigorous characterization. The specific substrate types include oc,P-unsaturated acids [20] 21 and esters [20] 22 hydroxychalcones [21] 23 a,P-enones [20] 24 2-cyclohexenones [20] 25 methylene-P-lactones [22] 26 tetracyclone [20] 27 and naphthaquinone [16] 28. The particular advantage of the dioxirane methodology is that labile functional groups, e.g. the phenolic moiety in the chalcones, do not require protection. 

Another type of catalyst successfully used in the enantioselective epoxidation of ( )-enones 52 is guanidine (Scheme 4.8). Thus, derivative 54a was able to perform the epoxidation of chalcone by using NaClO in toluene at 0 C [57]. Pentacyclic guanidine 54b (10 mol%), which have a characteristic closed-type cavity, gave products in moderated yields (22-99%) and enantioselectivities (35-60% ee) using iert-butyl hydroperoxide as oxidant in a liquid-liquid dichlo-romethane and aqueous potassium hydroxide two-phase system at 0°C. In contrast to that, tricyclic guanidine 54c (10 mol%) afforded the corresponding epoxides almost quantitatively with the same levels of enantioselectivity in similar reaction conditions [58]. 

---