Catalytic Asymmetric Synthesis of α,α,α-Trifluoromethylamines by the Copper-Catalyzed Nucleophilic Addition of Diorganozinc Reagents to Imines

Lauzon, Caroline; Charette, André B.

doi:10.1021/ol0607847

Cited by 134 publications

(50 citation statements)

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“…Although there exist several methods to generate trifluoroethylamines, [6][7][8][9][10][11][12][13] there is a significant requirement on new synthetic approaches. A frequently deployed methodology for the introduction of the trifluoromethyl group is the addition of Rupperts reagent to imines.…”

Section: Resultsmentioning

confidence: 99%

“…In the literature the addition of ZnMe 2 to trifluoroketimines is described, even in a catalytic asymmetric manner. [7,17] However, the use of trimethylaluminium for the alkylation in this synthetic approach is completely unknown. So, we herein report the first example for the addition of trialkylaluminium reagents to CF 3 -ketimines to generate a-trisubstituted amines.…”

Section: Resultsmentioning

confidence: 99%

“…Especially amide bond mimics are an interesting topic in current research due to the rapid in vivo degradation and low bioavailability of the parent peptides. In particular, atrifluoroA C H T U N G T R E N N U N G methylated amines are of ongoing significance [6][7][8][9] as amide bond mimics. [10] Since the investigation of the cathepsin K inhibitor Odanacatib (Figure 1), which is now in phase III clinical trial, there is an increased demand for trifluoroethylamines themselves as well as new synthetic accesses to this substance class.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expedient Trimethylaluminium‐Promoted One‐Pot Synthesis of Functional Heteroaromatic and Carbocyclic Trifluoroethylamines

2010

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The synthesis of trifluoroethylamines as amide bond mimics is an interesting topic in current research. They are well known tools in pharmaceutical and agrochemical industry. Other methods described in literature are often restricted to few substrates. We herein report a new synthetic approach towards this class of substances. First, the trimethylaluminium-promoted generation of a trifluoromethyl-ketimine from the corresponding trifluoromethyl ketone and an aniline derivative was investigated. Next, the ketimine was converted into the trifluoro-A C H T U N G T R E N N U N G ethylamines in a one-pot reaction by simple addition of borane-methyl sulfide complex.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expedient Trimethylaluminium‐Promoted One‐Pot Synthesis of Functional Heteroaromatic and Carbocyclic Trifluoroethylamines

2010

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“…The Kresze reaction has also been used in the synthesis of N-phosphinoyl imines derived from nonenolizable aldehydes, although usually in modest yields [25,26]. The N-phosphinoyl imine derived from trifluoromethyl ketones can be prepared via the ethanolate intermediate (Scheme 1.7) [27]. This adduct is directly used in the subsequent nucleophilic addition reaction.…”

Section: N-phosphinoyl Iminesmentioning

confidence: 99%

Stereoselective Synthesis of α‐Branched Amines by Nucleophilic Addition of Unstabilized Carbanions to Imines

Charette¹

2010

Chiral Amine Synthesis

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“…[24b, [28][29][30] In conclusion, we have reported the first procedure for the catalytic enantioselective alkynylation of N-sulfonyl aldimines to give N-sulfonyl-protected propargylic amines by using dimethylzinc and binol-type ligands. Substitution of the binol ligand at the 3,3' positions seems to be essential for obtaining high enantioselectivities.…”

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confidence: 99%

Highly Enantioselective Zinc/Binol‐Catalyzed Alkynylation of N‐Sulfonyl Aldimines

et al. 2008

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The catalytic enantioselective formation of new C À C bonds is an important class of organic reactions.[1] Among them, the asymmetric additions of terminal alkynes to C=O and C=N bonds are two of the most important objectives in organic synthesis; the resulting chiral propargylic alcohols and amines are versatile building blocks for the synthesis of a wide range of natural products and pharmaceuticals. Some excellent work has been reported on the asymmetric addition of alkynes to carbonyl compounds resulting in high ee values. [2] However, the practical enantioselective alkynylation of imines and imine derivatives to form propargylic amines is challenging because of the poor electrophilicity of the azomethine carbon. [3] In this context, most of the studies reported so far deal with the catalytic enantioselective alkynylation of N-aryl imines by using Cu I salts in combination with nitrogen-containing ligands. The leading studies of this reaction with N-aryl imines have been developed by Wei et al., [4] Bisai and Singh, [5] and Benaglia and co-workers [6] ; and Knochel and co-workers [7] and Carreira and co-workers [8] reported using iminium intermediates generated in situ in a three-component synthesis of propargylic amines.[9] Other methods, which do not make use of copper complexes as the catalyst, have also been described. Hoveyda and co-workers have used peptide-based ligands in combination with Zr-(OiPr) 4 ·HOiPr to catalyze the addition of preformed mixed alkynylzinc reagents to various N-aryl aromatic imines, which gives good results with trimethylsilylethyne and lower enantioselectivities with aryl-substitued alkynes.[10] Jiang and Si have described the addition of alkynes to a trifluoromethyl activated cyclic imine by using a stoichiometric amount of a chiral amino alcohol ligand.[11] Recently, Bolm and co-workers have described the use of dimethylzinc to catalyze the addition of terminal alkynes to N-aryl and N-protected imines in the absence of ligands.[12] An enantioselective version has been implemented by these authors for o-methoxyanilinederived imines by using a relatively large loading (40 mol %) of the amino alcohol ligands. [13] In contrast, N-acyl-and Nsulfonyl-protected imines show enhanced reactivity because of the electron-withdrawing character of the protecting group.The alkynylation of these substrates lead to protected propargylic amines. The highly enantioselective alkynylation of N-acyl imines has been carried out by using chiral alkynylboronates [14] and alkynylboranes, [15] which are based on the binol and the borabicyclo[3.3.2]decane scaffolds, respectively, as reagents. However, to the best of our knowledge, the enantioselective alkynylation of N-tosyl imines has not been reported so far. Because of the increased reactivity of N-sulfonyl imines and the findings reported by Bolm and co-workers, [12] we envisioned a dimethylzinc-mediated catalytic enantioselective alkynylation of N-sulfonyl imines by using an appropriate ligand (Scheme 1). Binol-type ligands were chosen in our stud...

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Catalytic Asymmetric Synthesis of α,α,α-Trifluoromethylamines by the Copper-Catalyzed Nucleophilic Addition of Diorganozinc Reagents to Imines

Cited by 134 publications

References 28 publications

Expedient Trimethylaluminium‐Promoted One‐Pot Synthesis of Functional Heteroaromatic and Carbocyclic Trifluoroethylamines

Expedient Trimethylaluminium‐Promoted One‐Pot Synthesis of Functional Heteroaromatic and Carbocyclic Trifluoroethylamines

Stereoselective Synthesis of α‐Branched Amines by Nucleophilic Addition of Unstabilized Carbanions to Imines

Highly Enantioselective Zinc/Binol‐Catalyzed Alkynylation of N‐Sulfonyl Aldimines

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