The first enantioselective aza-Darzens reaction of cyclic imines with a-halogenated ketones was realized under mild reaction conditions by using amino-acid-derived bifunctional phosphonium salts as phase-transfer promoters.A variety of structurally dense tri-and tetrasubstituted aziridine derivatives,c ontaining benzofused heterocycles as well as spiro-structures,w ere readily synthesized in high yields with excellent diastereo-and enantioselectivities (up to > 20:1 d.r. and > 99.9 %ee). The highly functionalizedaziridine products could be easily transformed into different classes of biologically active compounds.Optically pure fused N-heterocycles,e specially aziridinecontaining molecules,are versatile intermediates in chemical synthesis, [1] and they are also prevalent building blocks in many biologically active compounds,i ncluding natural alkaloids and pharmaceutical agents (Scheme 1). [2] Accordingly, an umber of catalytic methods have been devised for the stereoselective construction of such structural motifs over the past two decades. [3][4][5][6][7][8][9] In this context, the aza-Darzens reaction becomes one of the most straightforward and efficient approaches for producing such ring systems. [5] Lewis and Brønsted acid catalyzed aza-Darzens of a-diazoacetates and imines,offering aziridines,were first disclosed by Brookhart, Te mpleton, and co-worker. [6] Thea symmetric variants of these acid-catalyzed aza-Darzens reactions were first reported by Wulff and co-workers [7] and further developed by Maruoka and co-workers, [8] and others, [9] particularly providing cis-o r/and trans-disubstituted aziridines in high yields with excellent stereoselectivities.However,less success has been achieved in direct construction of trisubstituted chiral aziridine scaffolds by this process,a nd only two examples were reported. [10] Maruoka and co-workers dis-closed achiral Brønsted acid catalyzed aziridination between N-a-diazoacylo xazolidinones and N-Boc imines,t hus creating trisubstituted chiral aziridine skeletons. [10a] Quite recently, Tr ost developed aZ n-ProPhenol catalyzed aza-Darzens reaction of chlorinated aromatic ketones with N-Boc aldimines,p roviding an ovel method for constructing trisubstituted chiral aziridine motifs. [10b] Although these impressive advances have been made,h ighly enantioselective preparation of trisubstituted aziridine rings is still synthetically challenging,let alone direct asymmetric synthesis of structurally dense tetrasubstituted chiral aziridine molecules.T ot he best of our knowledge,n og eneral and straightforward catalytic protocol to access optically pure tetrasubstituted aziridines has been reported so far. Therefore,i ti sh ighly desirable to explore autilitarian strategy to fill this void.In this study,w ea ttempted to develop an alternative approach to prepare structurally dense tri-and tetrasubstituted aziridines with readily available catalysts and reagents. In the past decades,a symmetric phase-transfer catalysis (PTC) has been recognized as ap owerful and versatile...

A highly enantiodivergent organocatalytic method is disclosed for the synthesis of atropisomeric biaryls via kinetic resolution inspired by a dipeptide‐phosphonium salt‐catalyzed Atherton–Todd (A‐T) reaction. This flexible approach led to both R‐ and S‐enantiomers by fine‐tuning of bifunctional phosphonium with excellent selectivity factors (s) of up to 1057 and 525, respectively. The potential of newly synthesized O‐phosphorylated biaryl diols was illustrated by the synthesis of axially chiral organophosphorus compounds. Mechanistic investigations suggest that the bifunctional phosphonium halide catalyst differentiates between the in‐situ‐generated P‐species in the A‐T process, mainly involving phosphoryl chloride and phosphoric anhydride, thus leading to highly enantiodivergent O‐phosphorylation reactions. Furthermore hydrogen bonding interactions between the catalysts and phosphorus molecules were crucial in asymmetric induction.

A practical, one‐pot protocol is described for the conversion of carboxylic acids into amides through carboxyl activation by the reagent combination of trimethyl phosphite and iodine. This method integrates several advantages: (1) it allows amines to be chemoselectively acylated with excellent results in the presence of sulfur and oxygen nucleophiles; (2) the method shows wide generality in respect of solvent, base, and substrate; (3) the reagents used are widely available and much less expensive than common coupling reagents, and (4) the process is remarkably convenient, permitting extraction, recrystallization, and column chromatography as optional work‐up procedures. The chemoselectivity and generality of the method, the low cost, and wide availability of reagents combined with the ease of use make it a very favorable process.

A highly diastereo-and enantioselective [4 + 1] cycloaddition of para-quinone methides to α-halogenated ketones was realized by bifunctional phosphonium salt catalysis, furnishing functionalized 2,3-dihydrobenzofurans in high yields and excellent stereoselectivities (>20:1 dr and up to >99.9% ee). Mechanistic observations suggested that the reaction underwent a cascade intermolecular substitution/intramolecular 1,6-addition process. DFT calculations revealed the presence of multiple H-bonding interactions between the catalyst and the enolate intermediate in the stereodetermining transition states.