Enones chalcone

Aryl-substituted enones (chalcones in particular) have been used as model substrates in studies of catalytic 1,4-additions vith organozinc reagents. Fig. 7.7 summarizes typical enantioselectivities achieved vith various chiral ligands. 

In contrast to the reaction products of the 1,3-dipolar cycloaddition to linear enones (chalcones and their derivatives), spiro- 1-pyrazolines 25-28 are stable heterocycles. Their isomerization into spiro-2-pyrazolines 29-31 can be carried out under acidic conditions at room temperature for 24 h in the case of the cis isomers, and for more than 1 month in the case of trans isomers [30, 41, 42, 43]. 

All of the methods are hmited to s-ds-enones (chalcones generally seem to work best) and much work remains to be done to expand the range of alkenes to include s-trans-enones, unsaturated esters, and imsaturated nitriles. There is, therefore, considerable scope for future research in this area. 

Cyclohexenones are thionated with LR (eq 3), but only the vinylogous dithioester (6) is a stable compound. Acyclic enones (chalcones) give on reaction with LR the enethione dimers (eq 4). ... 

The conjugate addition to acyclic enones is summarized in Table 5. The chiral hetero-cuprate derived from (S)-prolinol or cinchonidine produced products of low enantiomeric excess on treatment with chalcone (entries 3 and 4), while the cuprate from (S)-yV-methylpro-linol gave 64% ee (entry 6). Under more dilute conditions, 88% cc was obtained (entry 5). (2[Pg.909]

A series of chiral phosphinous amides bearing pendant oxazoline rings (50, Ri=H,Tr R2=H,Tr, 51, Ri=H,Tr R2=H,Tr and 54, Ri=H,Tr R2=H,Tr in Scheme 41) have been used as ligands in the copper-catalyzed 1,4-addition of diethylzinc to enones. Two model substrates have been investigated, the cyclic 2-cyclohexenone and the acyclic trans-chalcone. The addition products are obtained quantitatively in up to 67% ee [171]. 

In 2000, Gennaii et al. discovered a new family of chiral Schiff-base ligands, with the general structure, Af-alkyl-p-(A -salicylideneamino)alkanesulfonamide, depicted in Scheme 2.28. These ligands were successfully implicated in the copper-catalysed conjugate addition of ZnEt2 to cyclic enones (Scheme 2.28) and, less efficiently, to acyclic enones such as benzalacetone (50% ee) or chalcone... 

There are two distinct classes of compounds that fit the criteria mentioned above alkene-functionalized chalcone derivatives (Fig. IB) and enone-functionalized chalcone derivatives (Fig. 1C). Within each class, both aromatic and non-aromatic compounds exist. Those compounds functionalized at the alkene include i) 3-membered heterocycles, e.g., epoxide and aziri-dine compounds, ii) 5-membered aromatic derivatives including fused and non-fused compounds, and iii) 6-membered aromatic pyrazine compounds. The enone-functionalized compounds include i) 5-membered aromatics such as pyrazole and isoxazole compounds, ii) 5-membered non-aromatic compounds for example pyrazolines and isoxazolines, and iii) 6-membered non-aromatics where a discussion of heterocyclic and non-heterocyclic compounds will be given for completeness. 

Similarly, Scheme 44 indicates that Selvan et al. utilized -hydroxy enones (e.g., 169) to synthesize pyrazoles (e.g., 170) [87]. Although this example is a cur cumin analog and not a chalcone derivative, it has been included as this class of compounds exhibited anti-oxidant and COX-l/COX-2 activity. 

Aryl-substituted enones such as chalcone and benzalacetone have been used as model substrates in the study of asymmetric 1,4-addition of acyclic enones. Many chiral ligands have been found to afford good enantioselectivities (Scheme 19). Typical results are summarized in Table i 46>50 58-66... 

For epoxidation of chalcones using Ender s method, the results depend on the nature of the substrate. For the ( )-benzylideneacetophcnonc (R1, R2 = Ph), the enantiomeric excess was only 60 % using the same procedure as the one described above, whereas the polyleucine method furnished the epoxide with an enantiomeric excess > 95%. Table 4.3 gives some results of the epoxidation of some acyclic enones using Ender s method. 

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. 

Following work on Michael addition of triazoles to nitro-olefins (discussed in Sect. 2.5), bifunctional chiral thiourea catalysts were used in the addition of triazoles to chalcones [83]. The catalytic system was applicable to enones bearing aromatic groups of varying electronic natures to provide good yields and moderate selectivity. a-Cyanoacetates [84] were also applied in Michael addition to chalcones under similar catalytic conditions (Scheme 33). 

The synthesis of isoxazolines and pyrazolines via the Michael addition of hydro-xylamine and phenyl hydrazine to chalcones and related enones was also reported with activated Ba(OH)2 as a basic catalyst (293) (Scheme 45). In both cases, reactions were performed at reflux of ethanol, and excellent yields (65-80%) with 100% selectivity to the heterocyclic compounds were observed. Steric hindrance associated with the carbonyl compound as well as the electronic character of the substituents in the aromatic ring slightly affected the yields of the heterocyclic compounds. 

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). 

Another approach to secondary amines has been reported (J. Am. Chem. Soc. 125 16178, 2003) by Masakafsu Shibasaki of the University of Tokyo. Addition of methoxyamine to a chalcone 7 (alkyl enones work in slightly lower ) gives the amine 8. The amine 8 can be reduced with high stereocontrol to the amino alcohol 9. K-Selectride gives the complementary diastereomer. 

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