Dramatic Improvement of the Enantiomeric Excess in the Asymmetric Conjugate Addition Reaction Using New Experimental Conditions

Alexakis, Alexandre; Benhaim, Cyril; Rosset, Stéphane; Humam, Munir

doi:10.1021/ja025598k

Cited by 288 publications

(132 citation statements)

References 21 publications

(20 reference statements)

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“…It has been reported that copper sources and solvents influences the efficiency of the diethylzinc addition reaction. 31) Therefore, the reactions were carried out by using Cu(OTf) 2 instead of CuI. However, no significant change in the yields of 3a was observed ( Table 2, entries 4-7).…”

Section: Resultsmentioning

confidence: 97%

N-Heterocyclic Carbene Ligands in Copper-Catalyzed Addition of Diethylzinc to N-Sulfonylimines

Bakar

Suzuki

Sato

2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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N-Heterocyclic carbenes (NHCs) are strong s-donating species, showing coordination properties similar to those of phosphines.1,2) Initially, the widespread use of catalysts containing carbene ligands was limited due to their relatively difficult preparation. Since the discovery of stable carbenes by Arduengo 3) in 1991, interest in the use of N-heterocyclic carbene-metal complexes have increased, and it has been demonstrated that they are efficient catalysts in important chemical transformations such as Pd-catalyzed coupling reactions, 4) Ru-catalyzed olefin metathesis, 5) and Rh-catalyzed hydrosilylations. [6][7][8] NHCs have also attracted great attention as organocatalysts in several reactions (e.g., benzoin condensation, [9][10][11][12][13][14] Stetter reaction, [15][16][17] transesterification/acylation reactions, 18,19) and nucleophilic substitution reactions). [20][21][22] Recently, our research group as well as other groups have reported the cyanosilylation of aldehydes catalyzed by NHCs. [23][24][25][26] In the course of our studies on the use of NHCs in organic synthesis, we have found that copper-NHC complexes exhibit the ligand acceleration effect (LAE) in the addition of diethylzinc to N-sulfonylimines. The LAE of copper-NHC complexes was first reported in the addition of diethylzinc to cyclohexenone, 27) and later the asymmetric version of these conjugate addition reactions was accomplished by using chiral NHC ligands. 28,29) In this study, we report our results on the addition of diethylzinc to N-sulfonylimines by using catalytic amounts of copper-NHC complexes. Results and DiscussionIn order to examine the catalytic abilities of the copper-NHC complexes, an addition reaction of diethylzinc to N-(benzylidene)-p-methylbenzenesulfonamide (N-sulfonylimine) 1a 30) was carried out in the presence of 5 mol% of imidazolium salt 2a as a ligand source, 5 mol% of CuI, and 5 mol% of t-BuOK in toluene (Table 1). After reacting at room temperature for 1.5 h, the addition product 3a (50%) and the reduction product 4a (28%) were obtained (Table 1, entry 1). The formation of 4a could be due to the transfer of the b-hydrogen of the ethyl functionality to the CϭN bond of the N-sulfonylimine 1a. In the absence of 2a, the reaction afforded the desired product 3a in only 15% yield and afforded 4a as the major product (entry 2). The reaction without CuI at room temperature for 6 h afforded 3a and 4a in 31% and 22% yields, respectively (entry 3). These results indicate that the LAE of NHC is involved in the addition reaction. To increase the yield of 3a and to suppress the byproduct formation, the reaction was carried out at 0°C. It was observed that though the yield of 3a was increased to 65%, byproduct 4a (12%) was still obtained. Further lowering of the reaction temperature to Ϫ5°C led to the exclusive formation of 3a (entry 5).At Ϫ5°C, the addition reactions of diethylzinc to 1a were carried out by using imidazolium and imidazolinium salts 2b-d as ligand precursors, and the addition products 3a were isolated in go...

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Section: Resultsmentioning

confidence: 97%

N-Heterocyclic Carbene Ligands in Copper-Catalyzed Addition of Diethylzinc to N-Sulfonylimines

Bakar

Suzuki

Sato

2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Me2Zn is about 30 times less reactive, 28 and gives lower ee's, 29 although quite high in some cases (>95%). 30 Functionalized dialkylzincs afford comparable enantioselectivities as Et2Zn. 13,15,21 The compatibility of R2Zn with many functional groups is clearly an advantage of the methodology.…”

Section: Methodsmentioning

confidence: 99%

“…Copper (II) triflate is most often the salt of choice, although copper acetate (as hydrate) and copper thiophenecarboxylate (CuTC) show superior enantioselectivity in many cases. 8 A tentative catalytic cycle is shown in scheme 4, with a copper carboxylate. After, reduction to the Cu(I) species, a first transmetallation with dialkylzinc forms a zinc carboxylate associated with an alkyl copper.…”

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confidence: 99%

Asymmetric Organocopper Chemistry: Cu-Catalyzed Conjugate Addition and Allylic Substitution

Alexakis

2004

ACS Symposium Series

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This review deals with the most recent developments in the asymmetric conjugate addition and allylic substitution. For the conjugate addition, the best enantioselectivities (>99%) have been attained with dialkylzinc reagents and 0.5-2% CuX and 1-4% of a chiral trivalent phosphorus ligand. The γ-allylic substitution can be achieved equally well with, either dialkylzinc or Grignard reagents, and the same catalysts.Oragnocopper chemistry is a standard synthetic tool nowadays.1 There are thousands of natural products, which have been synthesized using this chemistry, at least in one step. The most popular reactions are 1) the conjugate addition, 2) the substitution, and particularly the allylic substitution, 3) the cleavage of epoxides, and 4) the carbocupration.

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“…In recent years, the design of new chiral ligands and catalysts has led to the realization of asymmetric Michael additions (10,11) and conjugate additions of dialkylzinc reagents (12,13) as well as arylboronic acids (14) with excellent levels of stereocontrol. For the asymmetric conjugate addition of alkylmetals, the subject of the present study, particularly effective methods based on alkylzinc reagents are now available for various cyclic enones (12,15) including the usually problematic cyclopentenones (16,17), lactones (18), nitroalkenes (19,20), and acyclic enones (21). Meanwhile, considerable difficulties have been experienced in attempts to reach high stereoselectivities in transition metalcatalyzed 1,4-addition of other organometallic reagents.…”

mentioning

confidence: 99%

Copper-catalyzed asymmetric conjugate addition of Grignard reagents to cyclic enones

Feringa

Badorrey²,

Peña³

et al. 2004

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

139

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It is no longer necessary to use dialkylzinc reagents to obtain enantioselectivities >95% in the copper-catalyzed asymmetric conjugate addition of organometallic compounds to cyclic enones. We now report how this can be accomplished by using inexpensive and readily available Grignard reagents. Screening of bidentate ligands provided outstanding results with copper complexes of commercially available chiral ferrocenyl-based diphosphines, in particular TaniaPhos and JosiPhos derivatives. These catalysts tolerate a range of Grignard reagents and different cyclic enones as substrates, leading to high regioselectivities and unprecedented enantioselectivities. Moreover, the reactions are successful with moderate catalyst loading (5 mol %) under mild conditions and in the absence of additives.

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Dramatic Improvement of the Enantiomeric Excess in the Asymmetric Conjugate Addition Reaction Using New Experimental Conditions

Cited by 288 publications

References 21 publications

N-Heterocyclic Carbene Ligands in Copper-Catalyzed Addition of Diethylzinc to N-Sulfonylimines

N-Heterocyclic Carbene Ligands in Copper-Catalyzed Addition of Diethylzinc to N-Sulfonylimines

Asymmetric Organocopper Chemistry: Cu-Catalyzed Conjugate Addition and Allylic Substitution

Copper-catalyzed asymmetric conjugate addition of Grignard reagents to cyclic enones

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