One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

Abstract

SummaryWe report here an efficient one-pot method for the synthesis of α,β-differentiated diamino esters directly from cinnamate esters using N,N-dichloro-p-toluenesulfonamide and benzylamine as nitrogen sources. The key transformations include a Cu-catalyzed aminohalogenation and aziridination, followed by an intermolecular SN2 nucleophilic ring opening by benzylamine. The reactions feature a wide scope of substrates and proceed with excellent stereo- and regioselectivity (anti:syn >99:1) .

Hypervalent Iodine (III) Catalyzed Regio- and Diastereoselective Aminochlorination of Tailored Electron Deficient Olefins via GAP Chemistry

“…These vicinal haloamines are versatile components in organic synthesis as their halogen moieties are labile to cross-coupling and substitution reactions. For example, haloamines are direct precursors to vicinal diamines (Ghorai et al, 2011 ; Xiong et al, 2014 ), α,β-dehydroamino acids (Chen et al, 2005 ), and aziridines (Van and De Kimpe, 2000 ; Schröder et al, 2017 ; Thakur et al, 2017 ). While the aminohalogenation is established for almost five decades now, it still faces shortcomings and limitations related to controlling regioselectivities and stereoselectivities, forming side products, which sometimes makes purification more difficult (Thakur et al, 2003 ; Bovino and Chemler, 2012 ).…”

Synthesis of Trifluoromethyl-Containing Vicinal Diamines by Asymmetric Decarboxylative Mannich Addition Reactions

“…In particular, such types of therapeutic activities as anti-cancer, -depressant, and -hypertensive are commonly associated with the 1,2-diamino group . This proven biological importance of vicinal diamines has stimulated considerable research activity; however, the development of new methods for more generalized and practical preparation of 1,2-diamines remains a significant challenge . Considering the exciting biological profile of vicinal diamines, the fluorinated derivatives of this class of compounds might be of great pharmaceutical potential. , In fact, it is quite established that introduction of fluorine into the molecules of biologically active compounds usually leads to improved efficacy, enhanced membrane permeability, and significantly higher stability toward oxidative degradation. , Furthermore, the current pharmaceutical industry critically depends on the new methodological developments in fluorine chemistry, aiming at preparation of novel fluorinated structural types .…”