Catalytic Enantioselective Conjugate Addition of Dialkylzinc Compounds to Chalcones

Abstract

Conjugate addition of diethylzinc to enones is catalyzed by a complex derived from Ni(acac)2 and C2-symmetric 2,2'-bipyridine 3 or chiral pyridines 5-12. The products are obtained with optical purities up to 89% ee. A strong positive nonlinear relationship between the enantiomeric excess of the ligand and the ee of the product has been observed. The factors which govern catalyst activity and enantioselectivity have been investigated.Carbon -carbon bond formation by conjugate addition of organometallic reagents to a$-unsaturated enones is an efficient and reliable method for the synthesis of P-substituted carbonyl compounds. In particular, organocopper reagents have successfully been applied to regio-, chemo-and stereoselective alkylations['l. Enanlioselectiue conjugate additions of organometallics were first described by Kretschmer['"I and Seebach[2bsc1 using sparteine or 1,4-(dialkylamino)-2,3-dimethoxybutane, respectively, as chiral coordinating ligands. Leyendecker['dl employed N-alkylprolinol, and recently Alexakis[''] used chiral phosphorus derivatives to induce asymmetry during the conjugate addition. Other efforts have focused on the development of organo(heter0)cuprates carrying optically active nontransferable ligands13]. In some cases, enantioselectivities up to 97% were achieved. In general, these methods require stoichiometric or often excess amounts of chiral reagents. Despite the increasing importance of catalytic enantioselective transformations, reports on chiral catalysts for conjugate addition reactions are still rarec4]. Lippard et al. reported that copper(1) complexes with bidentate N,N-dialkyl-substituted aminotropone imines catalyze the 1,4-addition of n-butylmagnesium chloride to ~yclohexenone[~1. The corresponding product was obtained with up to 74% ee. However, the scope of this reaction is rather limited, and other reactants gave products with very low enantiomeric excess. Jansen and Feringa described the conjugate addition of Grignard reagents to enones catalyzed by chiral zinc(I1) complexes derived from diamines and amino alcohols[61. With this system, optical yields up to 33% ee were achieved. Based on some earlier work by Luche et al.I7], Soai and co-workers developed an enantioselective modification of the nickel-catalyzed alkyl transfer from diorganozincs to enones [']. A complex prepared in situ from nickel acetylacetonate [Ni(acac),] and N,N-dialkylnorephedrine afforded the products with moderate to good enantioselectivity. The degree of asymmetric induction could then be substantially raised by the addition of achiral ligands such as 2,2'-bipyridine or 1, lOphenanthroline[8a1. Our interest in this area derived from our previous work on the enantioselective alkylation of aldehydes catalyzed by optically active bipyridines and pyridine derivative^ [^^'^]. We found that nickel complexes of C2-symmetric bipyridine 3["] catalyzed the conjugate addition of diethylzinc to chalcones and afforded addition products with high enantiomeric excess[121. In this paper, we describe further d...

Nonlinear Effects in Asymmetric Catalysis

“…Reetz noticed a (+)-NLE in the rhodium-catalyzed hydrogenation of olefin 161 in the presence of binol-derived monodentate phosphite 162 a [Eq. (50)]. [144] The theoretical curve, based on an ML 2 model with K = 4 and g = 0, was found to fit well with the experimental curve, and the stochastic formation of catalytically active homochiral and catalytically inactive heterochiral complexes was proposed.…”

“…Bolm et al [50] and Feringa and co-workers [51] reported (+)-NLEs for nickel-catalyzed 1,4-additions to enones. The authors proposed the intervention of [NiL 2 ] species in the catalytic cycle.…”

Enantioselective addition of phenylacetylene to N‐aryl arylimines catalyzed by Cu(II)‐pyridine containing N‐tosylatedaminoimine ligand complex

“…7,8 Bolm et al developed a series of substituted pyridyl alcohols in asymmetric diethylzinc addition to aldehydes and conjugate addition reactions of diethylzinc to chalcones. [9][10][11] They also reported the use of C2-symmetric chiral bipy ligands in enantioselective conjugate addition reactions such as diethylzinc addition to aldehydes, and enantioselective addition of alcohols and amines to meso-epoxides. [12][13][14] Lee described Monopyridyl bisimine ligands in Ru-catalyzed cyclopropanation of styrene.…”

A Chiral Pool Strategy for the Synthesis of Enantiopure Hydroxymethyl‐Substituted Pyridine Derivatives

“…[4] Further examples include palladium-catalysed allylic substitution reactions, [5] nickel-catalysed additions of organozinc compounds to enones [6] and asymmetric alkynylations of aldehydes. [7] Typically, enantiopure (hydroxymethyl)pyridine derivatives are prepared through asymmetric reductions of the corresponding ketones, diastereoselective additions of lithiated pyridine derivatives to chiral ketones or through resolution of racemic compounds.…”