Chalcone derivatives, asymmetric

A series of chiral p-hydroxysulfoximine ligands have been synthesised by Bolm et al. and further investigated for the enantioselective conjugate addition of ZnEt2 to various chalcone derivatives. The most eiScient sulfoximine, depicted in Scheme 2.33, has allowed an enantioselectivity of up to 72% ee to be obtained. These authors assumed a nonmonomeric nature of the active species in solution, as suggested by the asymmetric amplification in the catalysis with a sulfoximine of a low optical purity. 

The asymmetric epoxidation reaction with polyleucine as catalyst may be applied to a wide range of a, 3-unsaturated ketones. Table 4.1 shows different chalcone derivatives that can be epoxidized with poly-L-leucine. The substrate range included dienes and tctracncs151. Some other examples were reported in a previous edition161 and by M. Lastcrra-Sanchcz171. 

In 2006, Xu and Xia et al. revealed the catalytic activity of commercially available D-camphorsulfonic acid (CS A) in the enantioselective Michael-type Friedel-Crafts addition of indoles 29 to chalcones 180 attaining moderate enantiomeric excess (75-96%, 0-37% ee) for the corresponding p-indolyl ketones 181 (Scheme 76) [95], This constitutes the first report on the stereoselectivity of o-CSA-mediated transformations. In the course of their studies, the authors discovered a synergistic effect between the ionic liquid BmimBr (l-butyl-3-methyl-l/f-imidazohum bromide) and d-CSA. For a range of indoles 29 and chalcone derivatives 180, the preformed BmimBr-CSA complex (24 mol%) gave improved asymmetric induction compared to d-CSA (5 mol%) alone, along with similar or slightly better yields of P-indolyl ketones 181 (74-96%, 13-58% ee). The authors attribute the beneficial effect of the BmimBr-D-CSA combination to the catalytic Lewis acid activation of Brpnsted acids (LBA). Notably, the direct addition of BmimBr to the reaction mixture of indole, chalcone, d-CSA in acetonitrile did not influence the catalytic efficiency. 

Since Corey s group first reported 0(9)-allyl-N-(9-anthracenylmethyl) cinchonidi-nium bromide as a new phase-transfer catalyst [13], its application to various asymmetric reactions has been investigated. In particular, this catalyst represents a powerful tool in various conjugated additions using chalcone derivatives (Scheme 3.2). For example, nitromethane [14], acetophenone [15], and silyl eno-lates [16] produce the corresponding adducts in high enantioselectivity. When p-alkyl substrates are used under PTC conditions, asymmetric dimerization triggered by the abstraction of a y-proton proceeds smoothly, with up to 98% ee [17]. 

The catalytic asymmetric epoxidation of electron-deficient olefins has been regarded as one of the most representative asymmetric PTC reactions, and various such systems have been reported (Scheme 3.12). Lygo reported the asymmetric epoxidation of chalcone derivatives through the use of NaOCl [30,31], while Shioiri and Arai used aqueous H202 as an oxidant, their results indicating hydrogen bonding between the catalyst and substrates because an OH functionality in the catalyst was essential... 

The Wang group also reported the asymmetric epoxidation of chalcone derivatives with their polymer-supported dimeric PTC 61 using fert-butyl hydroperoxide as an oxidant (Scheme 4.18) [23]. 

Cobalt(II) complexes prepared in situ from (AcO Co and two novel chiral spiro nitrogen-containing ligands, 7,7/-bis(2-pyridinecarboxamido)-l,l/-spirobiindane (SIPAD) and 7,7/-bis(2-quinolinecarboxamido)-l,l/-spirobiindane (SIQAD), are efficient cata- lysts for the asymmetric Michael addition of malonates to chalcone derivatives. The alkylation products were obtained in high yields with moderate enantioselectives.169... 

As the first example of asymmetric synthesis using chiral crystals involving solid-gas reaction, ) some other interesting examples of solid-gas reaction using chiral crystals were reported. Reaction of chiral crystals of chalcone derivative with bromine in connection with rearrangement gave optically active dibromide in 8%... 

Table 20 Asymmetric Friedel-Crafts-type reactions of indole with chalcone derivatives using a chiral Hg-S.S -SiPhs-BINOL-barium catalyst...

In addition, catalyst 28 has been appUed in an organocatalytic asymmetric tandem Michael/aza-Henry reaction between chalcone derivatives and nitrometh-ane to afford the corresponding polysubstituted tetrahydroquinoline derivatives with good yields and high enantio- and diastereoselectivities [40]. 

Roberts has shown that the asymmetric epoxidation of chalcone can be catalysed by polyamino acid derivatives under non-aqueous conditions [13]. This improved reaction involves the use of a urea-hydrogen peroxide complex in THF, in the presence of an organic base (DBU) and immobilized poly-(L)-leucine. Under these conditions, the reaction of chalcone derivatives and related substrates provided the corresponding epoxides in 70-99% yield and 83-95% ee within 30 min. Several substrates with enolisable enones have also been epoxidized successfully [14]. 

Scheme 12.20 Asymmetric phase-transfer catalytic conjugate addition of 2-nitropropane to chalcone derivatives and its application to the synthesis of highly functionalized substituted pyrrolidines 95.

The first attempted asymmetric intermolecular Stetter reaction was reported by Enders and co-workers who showed in 1989 that reaction of n-butanal 142 with chalcone 143 in the presence of the NHC derived from thiazolium salt 144 generated Stetter product 145 in 39% ee but only 4% yield (Scheme 12.30) [66],... 

Bode and co-workers rendered this transformation asymmetric allowing access to a>cyclopentenes 244 with high enantioselectivity (Table 19) [128], Optimized reaction conditions include the use of A-mesityl substituted aminoindanol derived triazo-lium catalyst 214. When chalcone and derivatives we re subjected to the reaction conditions, ax-cyclopentenes were formed selectively. Although the substrate scope is also limited to P-aryl substituted enals, cis. trans ratios of up to >20 1 are observed. 

Gaul and Seebach showed that lithiated methylthiomethyl-substituted chiral oxazolidi-nones react with aldehydes, ketones, imines and chalcones (Scheme 41). In this case, the oxazolidinone is derived from diphenylvalinol. The products, with two new asymmetric centers, are formed in good yield and excellent diastereoselectivity.A detailed mechanistic study of this and related systems, using computational methods, IR and NMR... 

The synthetic protocol (Scheme 11.2) toward the flavan-3-ol permethylaryl ethers is based upon the transformation of rc7ro-chalcones into 1,3-diarylpropenes. These compounds are then subjected to asymmetric dihydroxylation to give diarylpropan-l,2-diols that are used as chirons for essentially enantiopure flavan-3-ols. The protocol is demonstrated in Scheme 11.2 for the synthesis of the tetra-(9-methyl-3-(9-acetyl derivatives 61a, 61b, 62a, and 62b of (-l-)-catechin (2), (—)-e 7-catechin, (—)-epicatechin (3), and (+)-e 7-epicatechin (4). ... 

Lygo and Wainwright recently reported a detailed study of the asymmetric phase-transfer mediated epoxidation of a variety of acyclic a,P-unsaturated ketones of the chalcone type. The third-generation cinchona-derived quats (8c and 7c), related to those discussed earlier in the alkylation section and Scheme 10.4, gave the best inductions (89% ee, 88 to 89, Scheme 10.13 and 86% ee for the pseudoenantiomeric catalyst 7c to give, as product, the enantiomer of 89). 

The 1,4-addition of diethylzinc to a, )-unsaturated ketones is catalyzed by nickel (II) complexes. Bolm showed in 1991 that a chiral amino alcohol derived from pyridine and Ni(acac)2 catalyzed the addition of diethylzinc to chalcone with a moderate asymmetric amplification.42 ML -type species are assumed, with the meso complex being the less reactive. Other examples of this reaction are collected in Table 2. 

The mechanism of the polyleucine-catalyzed epoxidation is still under investigation [74]. Kinetic studies indicate that the reaction proceeds via the reversible addition of chalcone to a polyleucine-bound hydroperoxide [75]. Recent discussions have included studies of asymmetric amplification polyleucine derived from non-enantiopure amino acid shows highly amplified epoxide enantiomeric excess, and the results fit a mathematical model requiring the active catalyst to have five terminal homochiral residues, as rationalized by molecular modeling studies [76]. 

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