Scalable, efficient process for the synthesis of (R)-3,5-bistrifluoromethylphenyl ethanol via catalytic asymmetric transfer hydrogenation and isolation as a DABCO inclusion complex

Hansen, Karl B.; Chilenski, Jennifer R.; Desmond, Richard; Devine, Paul N.; Grabowski, Edward J. J.; Heid, Richard; Kubryk, Michele; Mathre, David J.; Varsolona, Richard J.

doi:10.1016/j.tetasy.2003.08.043

Cited by 81 publications

(32 citation statements)

References 14 publications

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“…This methodology is very convenient, for the following reasons: 1) it is operationally simple; 2) low loadings of the metal catalysts are normally used; 3) it avoids the handling of hazardous chemicals, such as molecular hydrogen or metallic hydrides; 4) the isolation of the reduction products is facilitated by the fact that volatile reaction byproducts are formed, such as acetone or carbon dioxide; 5) the reactions can be performed in environmentally benign solvents, like water; [12] and 6) the methodology has been demonstrated to be applicable to industrial processes. [13] Although the ATH process has been widely applied to the synthesis of chiral secondary alcohols by the reduction of ketones, [6,14] the number of examples of the stereoselective synthesis of amines by this method is more limited. Ruthenium, [15] rhodium, and iridium complexes bearing chiral ligands, such as monotosylated di-A C H T U N G T R E N N U N G amines, b-amino alcohols, diphosphines, and N-heterocyclic carbenes, have been used as catalysts for the ATH of imines with alkyl, [6] aryl, [6, 14c] benzyl, [5a, 6, 14c] phosphinyl, [2,6] or sulfonyl [6, 14b] groups attached to the nitrogen atom, as well as endocyclic imines.…”

Section: Introductionmentioning

confidence: 99%

A Versatile Ru Catalyst for the Asymmetric Transfer Hydrogenation of Both Aromatic and Aliphatic Sulfinylimines

Pablo

Guijarro

Kovács

et al. 2012

Chemistry A European J

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A highly efficient Ru catalyst based on an achiral, very simple, and inexpensive amino alcohol ligand (2-amino-2-methylpropan-1-ol) has been developed for the asymmetric transfer hydrogenation (ATH) of chiral N-(tert-butylsulfinyl)imines. This complex is able to catalyze the ATH of both aromatic and the most challenging aliphatic sulfinylimines by using isopropyl alcohol as the hydrogen source. The diastereoselective reduction of aromatic, heteroaromatic, and aliphatic sulfinylketimines, including sterically congested cases, over short reaction times (1-4 h), followed by desulfinylation of the nitrogen atom, affords the corresponding highly enantiomerically enriched (ee up to >99 %) α-branched primary amines in excellent yields. The same ligand was equally effective for the synthesis of both (R)- and (S)-amines by using the appropriate absolute configuration in the iminic substrate. DFT mechanistic studies show that the hydrogen-transfer process is stepwise. Moreover, the origin of the diastereoselectivity has been rationalized.

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Section: Introductionmentioning

confidence: 99%

A Versatile Ru Catalyst for the Asymmetric Transfer Hydrogenation of Both Aromatic and Aliphatic Sulfinylimines

Pablo

Guijarro

Kovács

et al. 2012

Chemistry A European J

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“…It is an important intermediate in the synthesis of therapeutic agents such as the NK-1 receptor antagonist used for the treatment of emesis. 2 A single approach for the synthesis of 2 is the asymmetric reduction of 3,5-bis(trifluoromethyl)-acetophenone 1. There are various catalytic methods available such as direct enantioselective hydrogenation 3 or borane reduction 4 for the asymmetric reduction of 1.…”

Section: Introductionmentioning

confidence: 99%

Total production of (R)-3,5-bistrifluoromethylphenyl ethanol by asymmetric reduction of 3,5-bis(trifluoromethyl)-acetophenone in the submerged culture of Penicillium expansum isolate

Kurbanoğlu

Zilbeyaz

Taşkın

et al. 2009

Tetrahedron: Asymmetry

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“…Lonza used a proline-derived catalyst to manufacture 50 kg of an intermediate for Josiphos ligands [119]. Merck used the same catalyst to reduce bistrifluoro-acetophenone on kilogram scale but, compared to the results for the (transfer) hydrogenation processes described above, the TON (20-50) and TOF (*20 h -1 ) were much lower [117,120]. Sepracor also developed this technology for an aryl-c-keto ester with respectable ee-values but, again, low activity [121], while Merck reported a pilot process for the reduction of a more complex intermediate using the aminoindanol ligand N^O (see Fig.…”

Section: Aromatic Ketonesmentioning

confidence: 99%

Industrial Applications

Blaser¹,

Spindler²,

Thommen³

2006

The Handbook of Homogeneous Hydrogenation

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While hydrogenation is without doubt the most important catalytic methodology for the manufacture of fine chemicals, until now most reactions have been carried out with heterogeneous catalysts. Heterogeneous hydrogenation catalysts have an exceptionally broad applicability for the chemo-and diastereoselective reduction of various functional groups, are convenient to handle, and catalyst separation is usually straightforward [1]. Homogeneous catalysts have found application for a number of special selectivity problems, the most important of which is enantioselective hydrogenation. While this will be the dominant topic of this chapter, a few scattered reports have been made where achiral complexes such as the Wilkinson catalyst, RhCl(Ph 3 P) 3 , or Ru-phosphine complexes have been applied on an industrial scale. In this regard, we will mention three examples [2]: (i) the chemoselective hydrogenation of a,b-unsaturated aldehydes; (ii) the diastereoselective hydrogenation of a tetracycline antibiotic; and (iii) the chemoselective hydrogenation of avermectin derivatives.As already mentioned, the most important industrial application of homogeneous hydrogenation catalysts is for the enantioselective synthesis of chiral compounds. Today, not only pharmaceuticals and vitamins [3], agrochemicals [4], flavors and fragrances [5] but also functional materials [6,7] are increasingly produced as enantiomerically pure compounds. The reason for this development is the often superior performance of the pure enantiomers and/or that regulations demand the evaluation of both enantiomers of a biologically active compound before its approval. This trend has made the economical enantioselective synthesis of chiral performance chemicals a very important topic.Industrial interest in the application of enantioselective catalysts began in earnest during the mid-1960s when the first reports of successful enantioselective transformations with homogeneous metal complexes were published. Within a surprisingly short period, production processes for two small-scale products, l-dopa (hydrogenation) and cilostatin (cyclopropanation) were developed and implemented by 1279The Handbook of Homogeneous Hydrogenation. Edited by J. G. de Vries and C. J. Elsevier

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Scalable, efficient process for the synthesis of (R)-3,5-bistrifluoromethylphenyl ethanol via catalytic asymmetric transfer hydrogenation and isolation as a DABCO inclusion complex

Cited by 81 publications

References 14 publications

A Versatile Ru Catalyst for the Asymmetric Transfer Hydrogenation of Both Aromatic and Aliphatic Sulfinylimines

A Versatile Ru Catalyst for the Asymmetric Transfer Hydrogenation of Both Aromatic and Aliphatic Sulfinylimines

Total production of (R)-3,5-bistrifluoromethylphenyl ethanol by asymmetric reduction of 3,5-bis(trifluoromethyl)-acetophenone in the submerged culture of Penicillium expansum isolate

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