A Facile Stereocontrolled Synthesis of anti-α-(Trifluoromethyl)-β-amino Alcohols

Abstract

A short stereocontrolled preparation of anti-alpha-(trifluoromethyl)-beta-amino alcohols is described, involving an initial CF(3) transfer to cinnamaldehyde and a one-step, three-component condensation of 3,3,3-trifluorolactic aldehyde, an alkenyl (aryl) boronic acid, and an amine. Applying this methodology to chiral 3,3,3-trifluorolactic aldehyde allowed us to generate an amino alcohol enantioselectively in 92% ee.

Multicomponent Reactions with Organoboron Compounds

“…The wide availability of aryl and heteroaryl boronic acids makes our method highly versatile and convenient, affording a large variety of amino acid derivatives (e.g. [69][70][71][72]. This process was employed by Jiang [43] for the asymmetric synthesis of indolyl glycine derivatives 72, and was also employed in the solid phase [26,[44][45][46][47] Additional aspects of this method have been under investigation by us and others.…”

“…Given the presence of the amine component, it is noteworthy that the enantiomeric purity of the aldehyde is generally retained during the reaction, allowing the stereoselective synthesis of highly functionalized amino alcohols, including derivatives having the trifluoromethyl group (e.g. 176) [71].…”

Diastereoselective Synthesis of β‐Amino‐α‐(trifluoromethyl) Alcohols from Homochiral α‐Dibenzylamino Aldehydes

“…[15] We were interested in the use of Ruppert's reagent (TMSCF 3 ) as a trifluoromethylation agent because of the mild reaction conditions that promote the addition. Thus, the reaction of homochiral dibenzylamino aldehydes 1aϪf [16] with an excess (1.5 equiv.)…”

Einführung von Fluor und fluorhaltigen funktionellen Gruppen

“…[310] Das anhaltende Interesse an der kontrollierten Addition fluorierter Reagentien an Doppelbindungen führte zur Entwicklung der Lauroylperoxid-initiierten radikalischen Addition von Aminotrifluorethyldithiocarbamat an Alkene zu a-Trifluormethylaminen. [313] Studer und Li haben kürzlich die kontrollierte radikalische Trifluormethylaminoalkoxylierung nichtaktivierter Alkene mit dem Togni-Reagens II, TEMPO und Natriummetall beschrieben. [313] Studer und Li haben kürzlich die kontrollierte radikalische Trifluormethylaminoalkoxylierung nichtaktivierter Alkene mit dem Togni-Reagens II, TEMPO und Natriummetall beschrieben.…”