Alpha,beta-unsaturated ketones are no longer the missing dipolarophiles in catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides. In the presence of Cu(I)-Fesulphos complexes as catalysts (5 mol %), these substrates combine high reactivity, wide substitution tolerance, moderate to good endo/exo selectivities, and high enantiocontrol. The endo/exo-diastereoselectivity of the reaction is strongly dependent on the cis or trans nature of the enone moiety.

An efficient catalytic enantioselective direct Mannich reaction of glycinate Schiff bases with aryl imines leading to anticonfigured orthogonally protected alpha,beta-diaminoesters has been realized. Keys to success in this new catalyst system are the use of Fesulphos/Cu(CH3CN)4PF6 (3-5 mol%) as a Lewis acid catalyst and readily available N-(8-quinolyl)sulfonyl-protected aldimines as substrates, affording excellent levels of diastereo- (typically anti/syn > 90:10) and enantiocontrol (typically > or = 90% ee). A remarkable feature of this catalyst system is that it allows the construction of products with a tetrasubstituted carbon stereocenter at C-alpha in a highly diastereo- and enantiocontrolled manner.

We report that 2-B(pin)-substituted allylic alcohols are good substrates for diastereoselective aziridinations in the presence of PhI(OAc)2 and N-aminophthalimide. Under the aziridination conditions, the valuable B–C bond remains intact, affording a variety of novel boron-substituted aziridines in good yields and excellent diastereoselectivities. Oxidation of the aziridine B–C bond enables generation of syn-1,3-aminohydroxy-2-ketones with high diastereoselectivity.

The construction of multiple stereocenters in flexible acyclic molecules in a single operation with complete diastereoand enantiocontrol constitutes a central challenge within the field of asymmetric catalysis. Driven by their biological significance and synthetic value, the synthesis of optically active a,b-diamino acids [1] via catalytic asymmetric direct Mannich reaction [2] between a prochiral nitrogen pronucleophile and an imine represents a touchstone in meeting this challenge and has recently emerged as an active research area.[3] Two complementary approaches are receiving great attention: the direct Mannich reaction of glycine ester Schiff bases (and related species) with imines [4] and the direct azaHenry reaction either between nitro compounds and aimino esters, [5] or between a-nitro acetates and imines. [6,7] Despite the development of very efficient organometallicbased and metal-free catalytic procedures, which show high asymmetric induction and syn-or anti-diastereocontrol, the development of diastereoselective switchable methods providing access to either syn-or anti-configured a,b-diamino acids remains elusive. Just one catalyst system has been shown to enable tuning of diastereoselectivity, leading to either anti-or syn-configured a,b-diamino acid esters in good yields and high diastereo-and enantioselectivities. [4i] In such an example, a dramatic anti/syn diastereoselectivity switch was achieved in the Mannich reaction of glycine derivatives with imines by modifying the electronic properties of the chiral phosphine ligand. As a useful complementary method, herein we describe that the syn-or anti-diastereoselectivity of the Mannich products can be efficiently switched by tuning the steric and electronic properties of the pronucleophile component (i.e., the glycinate imine) while maintaining the same catalyst system.Recently, we reported a route to anti-a,b-diamino acid derivatives based on the Cu I -Fesulphos-catalyzed reaction of glycine ester aldimine pronucleophiles with the readily available N-(8-quinolyl)sulfonyl aldimines [8] (Scheme 1 a). We envisioned that the use of ketimine-derived glycine pronucleophiles, instead of aldimine derivatives, could result in new critical steric interactions in the transition state that could potentially lead to a reversal in the sense of facial selectivity of the imine approach to the ester enolate, thus providing access to products with the opposite syn-configuration (Scheme 1 b).Our working hypothesis was validated in the reaction of the glycine methyl ester benzophenone Schiff base 2 a with differently N-protected aldimines 3 a-g under the optimized Fesulphos-Cu I catalyst system, [8,9] in all cases the syn-configured adduct being predominant in the reaction mixture (Table 1). However, very low syn-diastereocontrol was achieved with most of the protecting groups examined, except for the encouraging values provided by the Boc (substrate 3 a, entry 1) and N-(8-quinolyl)sulfonyl [10] (substrate 3 f, entry 6) groups. The nitrogen of the 8-quinolyl moiety ...

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