Copper Reagents:  A New and Efficient Solution for the Selective Addition of Metallated Propargylic Amines to Aldehydes

Bernaud, Frederic; Vrancken, Emmanuel; Mangeney, Pierre

doi:10.1021/ol034893m

Cited by 26 publications

(35 citation statements)

References 6 publications

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“…Unexpectedly anti-aminoalcohols were obtained with a better selectivity than with zinc derivatives. 5 The zincates reagents are often compared to cuprates in terms of reactivity 6 but a recent paper from Nakamura has pointed out the structural differences between these two 'ate' complexes. 7 Moreover, to our knowledge, no study on the addition of allenylzincates reagents to aldehydes has been performed so far.…”

Section: Methodsmentioning

confidence: 99%

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syn-Addition of Metallated Propargylic Amines to Aldehydes. A New Application of Triorganozincates

Bernaud¹,

Vrancken²,

Mangeney³

2004

Synlett

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Good syn-selectivities are obtained by addition of a di-tbutyl zincate reagent derived from a propargylic amine to aldehydes.The stereochemistry of the addition of allenic-propargylic organometallic reagents to aldehydes is widely attributed to the existence of two transition states, a cyclic one affording the anti-adduct or an open one affording the synadduct (Scheme 1). 1 As shown in Scheme 1, the cyclic transition state involves the activation of the aldehyde by the Lewis acidic metal of the organometallic reagent. Poor with lithium and Grignard derivatives, 2 the anti-selectivity is good with titanium, zinc, chlorostannyl, chlorosilyl and indium derivatives. 3 With non-Lewis acidic organometallic reagents such as trialkylstannyl or silyl derivatives and in the presence of an external Lewis acid, a synselective addition is obtained via the open transition state. 4 Scheme 1We have recently re-examined the diastereoselective addition of organozinc reagents (AZnBr), derived from the propargylic amine 1, to aldehydes. As expected, the antiaminoalcohols were obtained with good selectivities via the cyclic transition state (entry 1, Table 1). 5 To our knowledge no methodology affording syn-aminoalcohols from metallated propargyl amines is available. We postulated that any change in the Lewis acidity of the organometallic reagent would have a dramatic effect on the stereochemistry of this reaction. Accordingly, a lithiocyanocuprate was prepared and added to aldehydes. Unexpectedly anti-aminoalcohols were obtained with a better selectivity than with zinc derivatives. 5 The zincates reagents are often compared to cuprates in terms of reactivity 6 but a recent paper from Nakamura has pointed out the structural differences between these two 'ate' complexes. 7 Moreover, to our knowledge, no study on the addition of allenylzincates reagents to aldehydes has been performed so far. Therefore we decided to study the effect of the nature (AZnBr, AZnR, AZnR 2 , Scheme 2) of the zinc reagents derived from 1 on the stereochemistry of this reaction. First, isobutyraldehyde was added to the allenyl-Zn-butyl (AZnBu) reagent (Scheme 3), prepared as shown in Scheme 2, to give, in a good yield, the amino alcohol 2a in 82:18 ratio in favor of the anti-adduct (entry 2, Table 1). Therefore, the switch of AZnBr into AZnBu induced a slight decrease of the anti-selectivity (compare entries 1 and 2 in Table 1). No significant change in the selectivity was observed with AZnt-Bu (entry 3). Scheme 2 Preparation of zinc reagentsThe zincate reagent AZnEt 2 was then prepared from the lithio derivative by addition of diethylzinc (Scheme 2). To the purple solution of zincate was slowly added, at -85°C, a THF solution of isobutyraldehyde (Scheme 3, entry 4). It is interesting to note that, during the addition, a decoloration was observed indicating that the reaction was instantaneous. The aminoalcohol 2a was obtained in good yield and in a 1:1 syn:anti ratio. Therefore, the transformation of AZnBu into AZnEt 2 resulted in a decrease of the anti-select...

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Section: Methodsmentioning

confidence: 99%

“…The aminoalcohols 2 were isolated by silica gel chromatography purification (cyclohexane:EtOAc, 98:2). For spectral and analytical data of anti-aminoalcohols see ref 5. For the syn-aminoalcohols see ref.…”

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confidence: 99%

syn-Addition of Metallated Propargylic Amines to Aldehydes. A New Application of Triorganozincates

Bernaud¹,

Vrancken²,

Mangeney³

2004

Synlett

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“…This result prompted us to explore the synthesis of functionalized furans from various homopropargylic alcohols obtained on a multi-gram scale, by our recently described allenylcuprate chemistry [71–73]. In the meantime, Aponick [77] and Akai [78] described very similar results using Au(I)/Ag(I) catalysts.…”

Section: Reviewmentioning

confidence: 99%

“…In order to deactivate the triple bond toward nucleophilic addition, a TMS group was placed in the acetylenic position. This substrate, obtained from the addition of an allenyl(cyano)cuprate on butyraldehyde [71–73], was reacted with allyltrimethylsilane. The reaction was totally regioselective for the propargylic site.…”

Section: Reviewmentioning

confidence: 99%

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

Debleds¹,

Gayon²,

Vrancken³

et al. 2011

Beilstein J. Org. Chem.

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“…Table 4 lists the alkylations of aromatic aldehydes and Table 5 summarizes phenylacetylene additions to aliphatic and α,β-unsaturated aldehydes. Mangency and coworkers used ZnBr 2 in the selective additions of metallated propargylic amines to aldehydes [59]. Scheme 1 shows these transformations.…”

Section: Alkylation/alkynylation Of Aldehydesmentioning

confidence: 99%

Recently Developed Organometallic Complexes of Zn, Cu(Zn, Li), Fe, Ru and Less-used Ions. Use in Selective 1,2-or 1,4-Additions, Transfer Hydrogenations, Aldol Reactions and Diels-Alder Reactions

Zhu¹,

Jiang

Ren

et al. 2005

COS

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This review introduces the broad general topic of asymmetric organic synthetic reactions and reagents. Reagents containing both frequently used metallic ions, e.g. Zn ++ , Cu +(++) and Ru ++ , and rarely used ions, such as Ag + , employed in the construction of designed chiral centers, are updated here. Enantioselective 1,2-additions and 1,4-conjugate additions, transfer hydrogenations, and diasteroselective aldol reaction are discussed. The selectivities induced by chiral β-, δor γ-chiral amino alcohols, chiral diols, chiral binaphthyl derivatives, chiral P,N-containing auxiliaries, and other ligands used to prepare chiral metallic complexes, were compared in each reaction system. The use of two or more metallic ions with a single chiral ligand has now become a more popular strategy to catalyze chiral-center-controlled processes. For example, only diethylzinc was used in enantioselective additions to aldehydes in early studies. Recently, the combination of Et 2 Zn and Cu ++ in the selective additions has been used to achieve high ee% values and yields. Finally, quantum calculations have been used to obtain kinetic data to predict a reactions ee% values. For example, the calculated ∆G cal. values have a strong relationship with the obtained ∆G fit values which have the direct linkage with the ee% values. EntryActivator ee (%) at 0 °°°°C (config.) ee (%) at -45 °°°°C (config.)

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Copper Reagents: A New and Efficient Solution for the Selective Addition of Metallated Propargylic Amines to Aldehydes

Abstract: [reaction: see text] Anti alpha-amino-homopropargylic alcohols are prepared by addition of metallated propargylic amines to aldehydes. Among the four organometallic (LI, Zn, Ti, Cu) derivatives used, the most effective are the copper reagents.

Cited by 26 publications

References 6 publications

syn-Addition of Metallated Propargylic Amines to Aldehydes. A New Application of Triorganozincates

syn-Addition of Metallated Propargylic Amines to Aldehydes. A New Application of Triorganozincates

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

Recently Developed Organometallic Complexes of Zn, Cu(Zn, Li), Fe, Ru and Less-used Ions. Use in Selective 1,2-or 1,4-Additions, Transfer Hydrogenations, Aldol Reactions and Diels-Alder Reactions

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Copper Reagents: A New and Efficient Solution for the Selective Addition of Metallated Propargylic Amines to Aldehydes

Abstract: [reaction: see text] Anti alpha-amino-homopropargylic alcohols are prepared by addition of metallated propargylic amines to aldehydes. Among the four organometallic (LI, Zn, Ti, Cu) derivatives used, the most effective are the copper reagents.

Cited by 26 publications

References 6 publications

syn-Addition of Metallated Propargylic Amines to Aldehydes. A New ­Application of Triorganozincates

syn-Addition of Metallated Propargylic Amines to Aldehydes. A New ­Application of Triorganozincates

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

Recently Developed Organometallic Complexes of Zn, Cu(Zn, Li), Fe, Ru and Less-used Ions. Use in Selective 1,2-or 1,4-Additions, Transfer Hydrogenations, Aldol Reactions and Diels-Alder Reactions

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syn-Addition of Metallated Propargylic Amines to Aldehydes. A New Application of Triorganozincates

syn-Addition of Metallated Propargylic Amines to Aldehydes. A New Application of Triorganozincates