The Asymmetric Dialkylzinc Addition to Imines Catalyzed by [2.2]Paracyclophane-Based <i>N</i>,<i>O</i>-Ligands

Dahmen, Stefan; Bräse, Stefan

doi:10.1021/ja025831e

Cited by 146 publications

(62 citation statements)

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“…[10 -13] Within the last few years, various new paracyclophane ligands have been used for asymmetric catalysis. [14 -17] In particular, the asymmetric 1,2-addition reaction of zinc reagents [18] such as alkyl, [19 -21] alkenyl, [22] aryl [23] and alkynyl [24] zinc reagents with aldehydes or imines, [19,20,23] can be efficiently controlled by the application of hydroxy[2.2]paracyclophane ketimine ligands.[17]We recently reported the synthesis of the [2.2]paracyclophane-based ketimine ligands (R P ,S)-2, (S P ,S)-2, (R P ,S)-3, and (S P ,S)-3 and their application in asymmetric catalysis such as the addition of zinc reagents to aldehydes. [19] During these studies, we observed not only that these ligands are highly active, [21,25] but also that they display mismatched and matched cases.…”

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Planar‐ and Central‐Chiral N,O‐[2.2]Paracyclophane Ligands: Non‐Linear‐Like Effects and Activity

Lauterwasser¹,

Vanderheiden²,

Bräse³

2006

Adv Synth Catal

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The non-linear-like effect (NLLE), activity, temperature dependence, and kinetics of hydroxy-[2.2]paracyclophane ketimine ligands have been investigated with the 1,2-addition reaction of diethylzinc to cyclohexanecarbaldehyde. A linear correlation between the enantiomeric excess of AHPC ketimine ligands bearing a phenylethyl side group and the product was observed with 0.5 mol % of catalyst loading. On increasing the catalyst loading to 4 mol %, a precipitate of the inactive heterochiral species was formed and resulted in a positive nonlinear-like effect. The enantiomeric ratio was found to have linear temperature dependence.Keywords: asymmetric catalysis; catalytic activity; non-linear-like effect; paracyclophanes Asymmetric catalysis often displays a relationship between selectivity and reactivity. Intricate molecular mechanisms with a number of rate constants often lead to complex rate laws. The latter have not been elucidated in most cases although attempts have been made to unravel them.[1] Features such as non-linear effects, [2] autocatalysis, [3] reservoir effects, chiral poisoning, [4] and asymmetric activation [5] have been discovered in asymmetric catalytic reactions.[6] In particular, the strong non-linear effect associated with Noyoris DAIB ligand in the addition of diethylzinc to benzaldehyde has been thoroughly investigated.[7a]Since the initial reports of Reich and Cram, [8] the field of [2.2]paracyclophane chemistry has grown considerably.[9] The chemical behavior of [2.2]paracyclophanes is currently well understood allowing predictable modification of this relatively stable class of molecules. [10 -13] Within the last few years, various new paracyclophane ligands have been used for asymmetric catalysis. [14 -17] In particular, the asymmetric 1,2-addition reaction of zinc reagents [18] such as alkyl, [19 -21] alkenyl, [22] aryl [23] and alkynyl [24] zinc reagents with aldehydes or imines, [19,20,23] can be efficiently controlled by the application of hydroxy[2.2]paracyclophane ketimine ligands.[17]We recently reported the synthesis of the [2.2]paracyclophane-based ketimine ligands (R P ,S)-2, (S P ,S)-2, (R P ,S)-3, and (S P ,S)-3 and their application in asymmetric catalysis such as the addition of zinc reagents to aldehydes. [19] During these studies, we observed not only that these ligands are highly active, [21,25] but also that they display mismatched and matched cases. [19,22] In general, the [2.2]paracyclophane backbone determines the configuration of the product. However, it was possible to finetune the ligand system by adjusting the side groups.The successful applications of these [2.2]paracyclophane-based ligands led to further investigations of this system. In this manuscript, we disclose our findings which lead to a deeper understanding of this ligand class. We present studies of the non-linear-like effect (NLLE) [26] with the enantiomeric pairs 1 and 3, respectively. In addition, we investigated the activity of the diastereomers (R P ,S)-2 and (S P ,S)-2 and the diaste...

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Planar‐ and Central‐Chiral N,O‐[2.2]Paracyclophane Ligands: Non‐Linear‐Like Effects and Activity

Lauterwasser¹,

Vanderheiden²,

Bräse³

2006

Adv Synth Catal

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“…Catalytic asymmetric nucleophilic addition reactions of organometallic reagents to imines have been reported with Ntosylimines (11,12), N-arylimines (13)(14)(15), and N-acylimines (16,17) as amine precursors. The cleavage of the protecting group leads to the ␣-chiral amine; however, in the former two cases, harsh conditions are usually necessary [N-tosyl, SmI 2 ; N-aryl, ceric ammonium nitrate or PhI(OAc) 2 ; N-formyl, H 3 O ϩ , heat].…”

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Catalytic asymmetric addition of diorganozinc reagents to N -phosphinoylalkylimines

Côté

Boezio

Charette

2004

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

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The synthesis of ␣-chiral amines bearing two alkyl groups has been hampered by the accessibility and stability of the alkylimine precursor. Herein, we report an efficient strategy to generate the alkyl-substituted imine in situ that is compatible with the MeDuPHOS monoxide⅐Cu(I) catalyzed addition of diorganozinc reagents. The sulfinic acid adduct of the imine is readily prepared by mixing diphenylphosphinic amide, the aldehyde, and sulfinic acid. The sulfinic acid adduct is generally isolated by filtration. The addition of diorganozinc reagents in the presence of Me-DuPHOS monoxide⅐Cu(I) and the in situ-generated imines affords the corresponding ␣-chiral amines in high yields and enantiomeric excesses.

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“…Functionalized aldehydes, such as a,b-unsaturated aldehydes [26] (entries [18][19][20] or benzyloxyacetaldehyde (entries 21,22), were also tolerated.…”

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Second‐Generation N,O‐[2.2]Paracyclophane Ketimine Ligands for the Alkenylzinc Addition to Aliphatic and Aromatic Aldehydes: Scope and Limitations

et al. 2006

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Second generation N,O-[2.2]paracyclophane ketimine ligands were investigated for their ability to catalyze the 1,2-addition of alkenylzinc reagents to aliphatic and aromatic aldehydes with special focus on functionalized substrates. For aliphatic aldehydes, which have always been challenging in this field, remarkably high enantiomeric excesses could be determined (50-95 % ee). However, alkenylzinc reagents bearing heteroatoms proved to be demanding substrates for this system. Keywords: alkenylzinc reagents; asymmetric catalysis; chiral allylic alcohols; N,O ligands; paracyclophanes Chiral allylic alcohols are important targets in organic synthesis, especially in natural product synthesis. As intermediates they can be used in further reactions such as allylic substitution, dihydroxylation, ene reaction, cyclopropanation, bromination, or epoxidation. However, the lack of a powerful ligand system impedes the use of the 1,2-addition of alkenylzinc reagents to aldehydes as a key step in natural product synthesis because highly functionalized substrates must be tolerated and high enantiomeric excesses must be achieved.[1] The rare examples in the literature show mostly the use of divinylzinc and substrateinduced diastereoselectivity. [2] In the case of substrate toleration, the catalyzed alkenylzinc addition could be an appropriate method because of the relatively low reactivity of zinc diorganyls towards aldehydes and ketones in comparison to other organometal compounds.[3] However, investigations in this field are few. In contrast, alkyl transfer to aromatic aldehydes is one of the most studied enantioselective catalytic reactions, yet there are only a few examples with high enantiomeric excesses for aliphatic aldehydes.[4] The alkenylzinc transfer is even less investigated; however, interest in this reaction has increased throughout the last years. [5][6][7][8][9][10][11][12] One method elaborated by Oppolzer and Radinov produces mixed alkyl-alkenylzinc species in situ using a transmetalation protocol involving hydroboration of alkynes.[2]paracyclophane-based ligands produce results ranging from good to excellent for this type of reaction, whereas the scope is limited to aromatic aldehydes and fully branched aliphatic aldehydes.[11] Wipf et al. also reported the preparation of alkenylzinc reagents via transmetalation but using zirconium as metal. [9] A comprehensive survey of [2.2]paracyclophanebased ligands can be found in recent reviews.[13] The use of planar-chiral and central-chiral ligands based on paracyclophane systems has emerged en masse since the disclosures by Belokon, Rozenberg et al., [14,15] the Berkessel group, [16] and most notably the Hopf group.[17] Within the last years, various new paracyclophane ligands have been used for asymmetric catalysis. [18][19][20] In particular, the asymmetric 1,2-addition reaction of organozinc compounds such as alkyl-, [21] alkenyl-, [11] and alkynylzinc [22] reagents with aldehydes or imines, [21] respectively, can be efficiently controlled by the use of...

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The Asymmetric Dialkylzinc Addition to Imines Catalyzed by [2.2]Paracyclophane-Based N,O-Ligands

Cited by 146 publications

References 13 publications

Planar‐ and Central‐Chiral N,O‐[2.2]Paracyclophane Ligands: Non‐Linear‐Like Effects and Activity

Planar‐ and Central‐Chiral N,O‐[2.2]Paracyclophane Ligands: Non‐Linear‐Like Effects and Activity

Catalytic asymmetric addition of diorganozinc reagents to N -phosphinoylalkylimines

Second‐Generation N,O‐[2.2]Paracyclophane Ketimine Ligands for the Alkenylzinc Addition to Aliphatic and Aromatic Aldehydes: Scope and Limitations

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