Enantioselective addition of organozinc reagents to aldehydes

Soai, Kenso; Niwa, Seiji

doi:10.1021/cr00013a004

Cited by 1,286 publications

(401 citation statements)

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“…These studies provide a solution to a long-standing problem in synthetic organic chemistry: the catalytic synthesis of tertiary alcohols from ketones with high enantioselectivity. Unlike related additions of dialkylzinc reagents to aldehyde substrates, which are promoted by hundreds of catalysts (3,4), only a few systems will catalyze alkyl additions to ketones (1,2,(5)(6)(7)(8), and most of them use high catalyst loadings and long reaction times (6)(7)(8).…”

mentioning

confidence: 99%

Catalytic asymmetric addition of diphenylzinc to cyclic α,β-unsaturated ketones

García

Walsh

2004

Proc. Natl. Acad. Sci. U.S.A.

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We have examined the use of our bis(sulfonamide) diol ligand (1) in the asymmetric addition of phenyl groups to cyclic ␣,␤-unsaturated ketones. Good to excellent enantioselectivities have been obtained with cyclic enones bearing alkyl substituents in the 2 position (71-97% enantiomeric excess). Furthermore, excellent enantioselectivities have been observed in the asymmetric phenylation of cyclic enones with 2-iodo and 2-bromo substituents. The results of this study broaden the scope of the asymmetric additions to ketones promoted by the titanium catalyst derived from ligand 1.alkylation ͉ tertiary alcohols ͉ zinc ͉ titanium ͉ asymmetric catalysis W e recently developed a highly enantioselective titanium catalyst based on the bis(sulfonamide) diol ligand 1 (Fig. 1) for the asymmetric addition of alkylzinc reagents to ketones (Eq. 1; ref. 1). When cyclic ␣,␤-unsaturated ketones were used as substrates, we found that the asymmetric addition reaction could be coupled with a diastereoselective epoxidation by using molecular oxygen as the oxidant to provide a one-pot synthesis of epoxy alcohols with high enantio-and diastereoselectivity (Eq. 2; ref. 2). These studies provide a solution to a long-standing problem in synthetic organic chemistry: the catalytic synthesis of tertiary alcohols from ketones with high enantioselectivity. Unlike related additions of dialkylzinc reagents to aldehyde substrates, which are promoted by hundreds of catalysts (3, 4), only a few systems will catalyze alkyl additions to ketones (1, 2, 5-8), and most of them use high catalyst loadings and long reaction times (6-8).The successful use of ligand 1 in the alkyl additions to ketones led our group (9) and Yus and coworkers (10) to examine the enantioselective phenylation of acyclic ketones with ZnPh 2 . The only previous results in the catalytic asymmetric phenylation of ketones were reported by Dosa and Fu in 1998 (11). In this pioneering work, these authors used Noyori's amino alcohol ligand, (ϩ)-3-exo-(dimethylamino)isoborneol [(ϩ)-DAIB] (12, 13), and diphenylzinc (3.5 eq). Initially, the reaction gave low yields and moderate enantioselectivities. It was found, however, that addition of 1.5 eq of methanol to the diphenylzinc resulted in formation of a mixed alkoxy phenyl zinc reagent that led to increased yields and enantioselectivities (Eq. 3) (11). Under these conditions, excellent enantioselectivities were obtained with substituted propiophenones [86-91% enantiomeric excess (ee)], and acetophenone derivatives afforded enantioselectivities as high as 80%. In the case of cyclohexyl methyl ketone and 3-methyl-2-butanone, the reaction proceeded with 75% and 60% enantioselectivities, respectively. Yields in the phenylation reaction with DAIB ranged from 53% to 91%. In contrast to the phenylation of ketones, several highly enantioselective catalysts have been developed for the asymmetric addition of phenyl groups to aldehydes (14-20).In our initial study on the addition of diphenylzinc to acyclic ketones with ligand 1, we found that enantio...

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confidence: 99%

Catalytic asymmetric addition of diphenylzinc to cyclic α,β-unsaturated ketones

García

Walsh

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…[1][2][3][4][5][6][7][8][9][10][11][12] Additionally, the reaction leads to secondary alcohols, which are valuable chiral building blocks 13,14 for the preparation of natural products or new materials with interesting physicochemical properties, 2,9 such as chiral liquid crystals 15 (Scheme 1). Although many chiral ligands for the reaction have been described so far, most of them being N,N-dialkyl amino alcohols (e.g.…”

Section: Introductionmentioning

confidence: 99%

Different influence of polyoxygenation on the catalytic activity of amido- versus amino-isoborneols

Sánchez‐Carnerero¹,

Engel²,

Maroto³

et al. 2011

Arkivoc

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“…1 Recently, the catalytic enantioselective addition of terminal alkynes to aldehydes has generated a tremendous amount of interest. [2][3][4][5][6][7][8][9][10][11] Since the first efficient asymmetric alkynes addition to aldehydes was demonstrated by Soai 12 using (1S,2R)-N,N-dibutylnorephedrine, many chiral ligands, such as N-methylephedrine, [13][14][15] BINOL and its derivatives, 5,10,[16][17][18][19][20][21] and sulfonamides 22,23 have been used successfully in this reaction. Other chiral ligands, such as amino alcohols, 24,25 oxazoline, [26][27] and imino alcohol, 28 have also been reported to catalyze this reaction.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective addition of phenylacetylene to aldehydes catalyzed by polymer‐supported titanium(IV) complexes of β‐hydroxy amides

Hui

Huang

et al. 2009

Chirality

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A series of polymer-supported chiral b-hydroxy amides and C 2 -symmetric b-hydroxy amides have been synthesized and successfully used for the enantioselective addition of phenylacetylene to aldehydes. High yields (up to 93%) and enantioselectivities (up to 92% ee) were achieved by using polymer-supported chiral bhydroxy amide 4b. The resin 4b is reused four times, giving the product with enantioselectivity 80% ee. Fortunately, it is found that this heterogonous system is suitable not only for aromatic aldehydes but also aliphatic aldehyde.

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Enantioselective addition of organozinc reagents to aldehydes

Cited by 1,286 publications

References 49 publications

Catalytic asymmetric addition of diphenylzinc to cyclic α,β-unsaturated ketones

Catalytic asymmetric addition of diphenylzinc to cyclic α,β-unsaturated ketones

Different influence of polyoxygenation on the catalytic activity of amido- versus amino-isoborneols

Enantioselective addition of phenylacetylene to aldehydes catalyzed by polymer‐supported titanium(IV) complexes of β‐hydroxy amides

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