Simple and convenient synthesis of 3,5-bis-(trifluoromethyl)benzylamine via biomimetic 1,3-proton shift reaction

Soloshonok, Vadim A.; Yasumoto, Manabu

doi:10.1016/j.jfluchem.2006.03.013

Cited by 15 publications

(5 citation statements)

References 18 publications

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“…The introduction of the bis(trifluoromethyl)-containing fragment was achieved by alkylation of 836 with bromide 837 , and then the protecting group was removed to yield compound 839 . It should be noted that an alternative approach may involve using 3,5-bis(trifluoromethyl)benzylamine, which can be conveniently prepared by biomimetic transamination . The remaining prochiral centers both derived from the raw material, methyl trans -4-formylcyclohexanecarboxylate ( 840 ), which was reacted with 839 through a reductive amination reaction, and finally evacetrapib ( 824 ) was easily accessed by converting the ester group to a carboxylic acid .…”

Section: Compounds Containing Two Trifluoromethyl Groupsmentioning

confidence: 99%

Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas

et al. 2016

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Section: Compounds Containing Two Trifluoromethyl Groupsmentioning

confidence: 99%

Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas

et al. 2016

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“…In fact, the nonreductive transamination of ketones usually occurs with base-catalyzed 1,3-proton shift of imines and subsequent hydrolysis, although acidic or thermally induced tautomerization of fluorinated imine-derivatives have been recently proposed.…”

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confidence: 99%

Exploiting the CNC Side Chain in Heterocyclic Rearrangements: Synthesis of 4(5)-Acylamino-imidazoles

et al. 2010

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A new variation on the Boulton-Katritzky reaction is reported, namely, involving use of a CNC side chain. A novel Montmorillonite-K10 catalyzed nonreductive transamination of a 3-benzoyl-1,2,4-oxadiazole afforded a 3-(alpha-aminobenzyl)-1,2,4-oxadiazole, which was condensed with benzaldehydes to afford the corresponding imines. In the presence of strong base, these imines underwent Boulton-Katritzky-type rearrangement to afford novel 4(5)-acylaminoimidazoles.

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“…As shown in Figure 11, fluoroalkyl/fluoroaryl aldehydes and ketones 38 (R = H, Alkyl, Aryl) can be efficiently reductively aminated to the target amines 41 using benzylamine [47][48][49][50][51][52] or its derivatives [53,54] as a source of nitrogen and reducing reagent at the same time, and triethylamine, or other organic bases, as a catalyst. Similarly, a-amino acids 42 can be easily prepared starting from a-keto carboxylic acids 38 (R = COOH) [55][56][57][58].…”

Section: Biomimetic Reductive Amination Of Fluorine-containing Carbonmentioning

confidence: 99%

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

2009

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Naturally occurring compounds containing a C-F bond are extremely rare; only a handful of fluorine-containing carboxylic acids have been described so far. By contrast, man-made fluorine-containing derivatives of all major classes of biologically important compounds are extremely promising medicinal targets used in the elucidation of biochemical, metabolic transformations and the development of new pharmaceuticals. Among the fluorine-containing derivatives of natural products, fluorinated analogs of amino acids are of particular interest and medicinal potential. This article presents a concise review of various synthetic methods, developed by the Kiev's school of bioorganic chemistry, for the preparation of fluorine-containing analogs of α- and β-amino acids, α-hydroxy acids, amines, as well as their phosphorus and sulfur-derived compounds, in enantiomerically pure form. One of the major methodological goals of the study was practicality, which is understood by us as stereochemical generality, operational convenience and synthetic affordance for each reaction step and isolation of the target products. The synthetic methods developed by our group can be roughly divided in two general categories: fluorine-adaptation of known synthetic approaches and discovery of new reactions. The former approach is most prominently represented by asymmetric homologation of nucleophilic glycine equivalents using fluorinated substrates via alkyl halide alkylations, aldol and Michael addition reactions. A plethora of discovered unexpected reaction outcomes, in particular stereochemical, are emphasized in this review and the particular role of fluorine, in altering the 'normal' reaction result, is explained. The latter direction is notably represented by the novel 1,3-proton shift reaction, a biomimetic reductive amination of fluorinated carbonyl compounds to the corresponding amines and amino acids, as well as the development of α-fluoroalkyl epoxides as true fluorinated synthons for generalized asymmetric synthesis of various biologically relevant compounds. Despite the highly anticipated potential of fluorine-containing amino compounds, their medicinal chemistry still remains underexplored. The major obstacle, in our opinion, is that these selectively fluorinated compounds are generally unavailable to the medicinal chemists for comprehensive, systematic study. We hope this review of synthetic methods will highlight and bring attention to particular types of fluorinated amino acids and related compounds readily available on a laboratory scale using methods developed by our group.

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Simple and convenient synthesis of 3,5-bis-(trifluoromethyl)benzylamine via biomimetic 1,3-proton shift reaction

Cited by 15 publications

References 18 publications

Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas

Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas

Exploiting the CNC Side Chain in Heterocyclic Rearrangements: Synthesis of 4(5)-Acylamino-imidazoles

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

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