Chalcone, diethylzinc

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]. 

A combined system consisting of a Ni(ll) complex and (2S)-DAIB effects the conjugate addition of diethylzinc to chalcone, resulting in the formation of (R)-1,3-diphenylpenta-1-one in 85% ee.°... 

In other diethylzinc studies, a neural network modelling approach has been used to predict the utility of new enantioselective catalysts,222 norephedrine-derived ligands with three stereogenic centres catalyse enantioselective addition to aldehydes and to chalcones,223 and a chiral sulfonamide ligand based on tartaric acid gives good ees in addition to both aldehydes and ketones.224... 

Novel norephedrine-based chiral ligands with multiple stereogenic centers have been conveniently prepared from norephedrine and. -substituted pyrrole.112 These novel chiral ligands have been used to catalyse the enantioselective addition of diethylzinc to aldehydes and to chalcone in high yields and with good to high enantioselectivities. 

Enantioselective catalytic conjugate addition of diethylzinc to chalcone using DBNE (Structure 1) as a chiral ligand27... 

Add a solution of chalcone in CH3CN (4 mL) and stir the mixture at room temperature for 20 min, then cool it to -30°C, then add dropwise diethylzinc, and stir the reaction mixture for 12 h at -30°C. 

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. 

Table 2 Catalytic asymmetric addition of diethylzinc to chalcone in the presence of 2 and 42-47...

The first example for the use of a diphosphine bearing stereogenic phosphorus atoms as a ligand in copper-catalyzed Michael additions has been reported by Inamoto and co-workers,265,265a who showed that the reaction of cyclohex-2-enone and the corresponding seven-membered enone with diethylzinc in the presence of Cu(OTf)2 and 307 (abbreviated as MiniPHOS) gave rise to the formation of the addition products with 70% and 97% ee, respectively (Scheme 84). The corresponding transformation of chalcone proceeded with 71% ee. Other simple diphosphines, however, displayed only moderate enantioselectivities in copper-catalyzed Michael additions.226... 

Optically active P-hydroxy /V-methyl sulfoximines have been used as catalysts for the enantioselective transfer of an ethyl group from diethylzinc to aldehydes to give secondary alcohols in enantiomeric excesses of 61-88%.127,135 Related chiral ligands have been used with nickel acetylacetone to promote the enantioselective Michael addition of diethylzinc to chalcones.136... 

Progress with regard to this undesired substrate specificity was achieved with the phosphorus amidite 10, which catalyzes not only Michael additions of organozinc reagents to cyclic enones but also to chalcone (11 R = Ph) and related acyclic substrates. In the case of the addition of diethylzinc to chalcone, a good enantioselectiv-ity of 87 % ee was observed [8]. 

Enantioselective Conjugate Addition. A Cu-(S,S)-NOR-PHOS catalyst has been used to promote conjugate addition of diethylzinc to a, 3-unsaturated ketones (eq 6), e.g., cyclohexen-2-one, chalcone, and benzalacetone. The use of (S,S)-CfflRAPHOS (7) and (R)-PROPHOS (8) afforded (S)-3-ethylcyclohexanone in somewhat improved chemical and optical yields relative to those obtained with Cu-(S,S)-NORPHOS catalyst. ... 

The asymmetric conjugate addition of diethylzinc with chalcone was also catalyzed by nickel and cobalt complex (Eq. (12.31)) [71]. A catalytic process was achieved by using a combination of 17 mol% of an aminoalcohol 34 and nickel acetylacetonate in the reaction of diethylzinc and chalcone to provide the product in 90% ee [72, 73]. Proline-derived chiral diamine 35 was also effective, giving 82% ee [74]. Camphor-derived tridentate aminoalcohol 36 also catalyzes the conjugate addition reaction of diethylzinc in the presence of nickel acetylacetonate to afford the product in 83% ee [75]. Similarly, the ligand 37-cobalt acetylacetonate complex catalyzes the reaction to afford the product in 83% ee [76]. 

Novel enantiopure C2 symmetric bis(oxazolines) 171 were obtained from tartaric acid and applied in the copper-catalyzed conjugate addition of diethylzinc to chalcone and 2-cydohexenone. The sense of induction was found to depend on the configuration of the stereogenic centers in the oxazoline rings and not in the 1,4-dioxane backbone <05TA2946>. 

Nickel complexes, prepared by the combination of Ni(acac)2 with a chiral P-ami-no alcohol [24,25] or a P-hydroxysulfoximine [26], catalyze the conjugate addition of diethylzinc to chalcone. Some asymmetric ampHfications have been observed. 

Using this exchange reaction, some functionalizations of aryl halides were examined. As an example of 1,2-addition to a carbonyl group, the arylzinc prepared from 4-iodobenzoate and diethylzinc in the presence of Bu-P4 base in THF was reacted with benzaldehyde to give the benzhydrol derivative in 78% yield. As for the 1,4-addition reaction, the arylzinc prepared similarly in THF was reacted with chalcone and the 1,4-adduct was obtained in 71% yield under copper-free reaction conditions. Allylation was also carried out in the absence of copper additive, and allylbenzoate was obtained in 98% yield. It has been reported that arylzinc compounds are inert to 1,4-addition and allylation reaction in the absence of additives and conventionally the employment of copper species has been widely used. However, in this case the Bu-P4 base is considered to promote the reactivity of arylzinc compounds toward electrophiles [59] (Scheme 5.38). 

Chiral ketones. A mixture of Ni(acac)2 and (lS,2R)-(-)-N,N-dibutylnorephedrine (both in catalytic amount) in acetonitrile stirred at 80° for 1 h under argon, solvent removed in vacuo, a little 2,2 -bipyridyl and acetonitrile added, stirred at 80° for 1 h, cooled to room temp., chalcone in acetonitrile added, after stirring for 20 min the mixture cooled to — 30°, treated dropwise with 1 M diethylzinc in toluene, stirred at — 30° for 12 h, then quenched with 1 M HCl - (R)-(-)-l,3-diphenylpentan-l-one. Y 47% (e.e. 90%). Acetonitrile (as ligand and/or solvent) was essential for high enantioselectivity. F.e. and ligands s. K. Soai et al., J. Chem. Soc. Chem. Commun. 1989, 516-7 s.a. J. Org. Chem. 53, 4148-9 (1988) review of asym. catalysis (industrial perspective) s. H.B. Kagan, Bull. Soc. Chim. France 1988, 846-53. 

There are many reports of copper-catalysed conjugate additions (1,4-addi-tions) of organometallic reagents to a,p-unsaturated ketones, which constitute examples of Michael reactions. The model Michael acceptors for cyclic and acyclic substrates are 2-cyclohexen-l-one (37) and zruw -chalcone (38) respectively whereas diethylzinc is the most widely used carbanionic reagent. These model reactions are depicted in Scheme 8.17. 

Cobalt(III)-SALEN complexes (see Fig. 20) were found to be efficient catalysts for asymmetric cyclopropanation (184). Co(acac)2 in the presence of chiral amino alcohols (derived from camphor) has been employed as a catalyst for the enan-tioselective addition of diethylzinc to chalcone (185). Axially chiral SALEN-type ligands possessing biphenyl-core as an element of chirality are efficient ligands for the enantioselective addition of diethylzinc to aldehydes. The formation of bimetallic species forming a chiral pocket was shown (186). 

Chiral Catalysts Containing Group 10 Metals (Ni, Pd, and Pt). The catalyst formed in situ from Ni(acac)2 and bomane aminoalcohols (DAB or DAIB) catalyze the enantioselective addition of diethylzinc to chalcones (254) (Fig. 21). Nickel(II)-chiral Schiff-base (the ligand derived from 1,2-diaminocyclohexane or 1,2-diaminopropane with pyrone derivative) complexes were efficient in epoxida-tion of nonfunctionalized olefins (255). Bis-ferrocenyl-triphosphane (PIGIPHOS) formed catalytically active complex with Ni(II) (256). Nickel-catalyzed asymmetric hydrocyanation of vinylarenes using glucose-derived phosphinite ligands was observed (257). 

De Vries, A. H. M., Jansen, J. P. G. A. and Feringa, B. L. (1994) Enantioselective conjugate addition of diethylzinc to chalcones catalyzed by chiral NiQI) aminoalcohols complexes. Tetrahedron 50,4479-4491... 

In 2010, chiral tridentate ligand 25, containing two stereogenic centres, one located on the sulfinyl sulfur atom and the other on the carbon atom in the aziridine moiety, was found by Lesniak and Kielbasinski to be a very efficient nickel ligand for the enantioselective conjugate addition of diethylzinc to chalcones as well as cyclohex-2-enone (Scheme 2.24). The... 

Scheme 2.24 Conjugate additions of diethylzinc to chalcones and cyclohex-2-enone with an in situ generated aziridine sulfoxide nickel catalyst and an in situ generated aziridine alcohol nickel catalyst.

In a second example, the conjugate addition of diethylzinc to chalcone in the presence of a catalyst generated from Ni(acac)2 and a chromium complex was investigated. Using 1 mol% of Ni(acac)2 and 10 mol% of complex 14, the (i )-conjugate addition ketone was obtained in 66% yield and in 36% ee (Scheme 6.20). The asymmetric induction is highly dependent on the amount... 

---