Substrate-directable chemical reactions

Hoveyda, Amir H.; Evans, David A.; Fu, Gregory C.

doi:10.1021/cr00020a002

Cited by 1,514 publications

(909 citation statements)

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“…The products of the asymmetric phenylation of cyclic enones are cyclic allylic alcohols that can be functionalized easily at the double bond in a diastereoselective step by taking advantage of the directing ability of the hydroxyl group (21). We are unaware of previous reports of catalytic asymmetric phenylation of this class of substrates.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

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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“…Less certain was the stereochemical outcome. Here we envisioned taking advantage of the directing ability of the C(17) hydroxyl (20,21). Support for this proposition derived from the crystal structure of (ϩ)-tedanolide (1), wherein the C(17) hydroxyl is oriented appropriately to direct epoxidation (Fig.…”

Section: Synthetic Strategymentioning

confidence: 95%

A unified approach to the tedanolides: Total synthesis of (+)-13-deoxytedanolide

Smith

Adams

Barbosa

et al. 2004

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

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A unified approach for the construction of the potent marine antitumor agents (؉)-tedanolide (1) and (؉)-13-deoxytedanolide (2) is described. Highlights of the synthetic strategy include the development of a versatile bifunctional dithiane-vinyl iodide linchpin, the unorthodox use of the Evans-Tishchenko reaction, and a late-stage high-risk stereocontrolled introduction of the C(18,19) epoxide to achieve a total synthesis of (؉)-13-deoxytedanolide (2).

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“…In der Enzymkatalyse sind diese auf einer "Intramolekularisierung" durch "aktives Volumen" basierenden Effekte ein allgemeines und bekanntes Phänomen. [232] Auf dirigierenden Effekten 87 basierende Reaktionen wurden in einem Übersichtsartikel von Hoveyda, Evans und Fu, [233] sowie kürzlich durch Breit et al ausführlich beschrieben. [229] Diese Effekte werden im modernen Reaktionsdesign immer wieder genutzt.…”

Section: Untersuchungen Zur Ts-abspaltung Am 3-hydroxypyridinunclassified

Totalsynthese von Nosiheptid

Wojtas

Riedrich

et al. 2016

Angewandte Chemie

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Eine Totalsynthese des bismakrocyclischen Thiopeptidantibiotikums Nosiheptid gelang durch den Aufbau einer voll funktionalisierten linearen Vorstufe und konsekutive Makrocyclisierungen. Schlüsselmerkmale waren eine kritische Makrothiolactonisierung und eine milde Entschützungsstrategie für den 3‐Hydroxypyridin‐Kern. Der Naturstoff war mit isoliertem authentischem Material im Hinblick auf spektroskopische Daten und antimikrobielle Aktivität identisch.

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Substrate-directable chemical reactions

Cited by 1,514 publications

References 0 publications

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

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

A unified approach to the tedanolides: Total synthesis of (+)-13-deoxytedanolide

Totalsynthese von Nosiheptid

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