Aminocatalysis, the activation of carbonyl compounds by enamines, iminium ions, or the SOMO-activation strategy, has become a fundamental approach in asymmetric synthesis. [1] Moreover, the catalytic modes of amines are still under expansion.[2] Recently, Jørgensen and co-workers developed dienamine catalysis by inverting the inherent reactivity of a,bunsaturated aldehydes, which acted as nucleophiles for direct enantioselective g amination with diethyl azodicarboxylate. [3] However, the synthetic potential of dienamine catalysis seems to be underestimated, and very limited progress has been made to date [4] in spite of the extensive studies on asymmetric aminocatalysis over the past decade.The development of efficient methodologies that enable simpler, cheaper, and more concise approaches to the generation of structural complexity with exquisite levels of stereocontrol remains a preeminent goal in modern organic chemistry. Recently, we presented a highly enantioselective inverse-electron-demand aza-Diels-Alder reaction of N-sulfonyl 1-aza-1,3-butadienes [5] and aliphatic aldehydes to form optically pure piperidines through enamine activation.[6-8] We were fascinated by the possible and conceptually unprecedented application of dienamine catalysis in an inverseelectron-demand aza-Diels-Alder reaction of a,b-unsaturated aldehydes with electron-deficient N-sulfonyl 1-aza-1,3-butadienes to construct chiral piperidine derivatives bearing several functional groups in a straightforward manner (Scheme 1).[9] We wondered whether the chemo-, regio-, and stereoselectivity of this complicated reaction could be controlled simultaneously in an elegant manner.We initially investigated the reaction of N-tosyl-1-aza-1,3-butadiene (2 a) and hexen-2-al (3 a) in a mixture of THF and H 2 O at room temperature under the catalysis of the chiral secondary amine 1 a (10 mol %) and benzoic acid (10 mol %).[10] The reaction proceeded smoothly with exclusive a regioselectivity. The chiral hemiaminal 4 a (an E/Z mixture) was isolated as the sole product. The oxidation of 4 a with pyridinium chlorochromate (PCC) gave a separable mixture of lactam 5 a and its Z isomer 6 a. Excellent enantioselectivity was observed for the formation of the E isomer 5 a (Table 1, entry 1). Similar results were obtained when the Scheme 1. Proposed inverse-electron-demand aza-Diels-Alder reaction of a dienamine intermediate generated in situ as an electron-rich olefin. Ts = 4-toluenesulfonyl.

The first chemo- and alpha-regioselective asymmetric Michael addition of gamma,gamma-disubstituted alpha,beta-unsaturated aldehydes to nitroolefins has been presented in excellent diastereo- and enantioselectivities (dr up to >99:1, 93-96% ee) via dienamine catalysis. The Michael adducts have been efficiently converted to a number of optically pure cyclic frameworks with versatile scaffold diversity.

The first highly enantioselective direct alpha-amination of aryl ketones was reported to be catalyzed by organic primary amines derived from cinchona alkaloids. Excellent enantioselectivities (88-99% ee) have been achieved for a broad spectrum of aryl ketones. The presence of 4 A molecular sieves was of great assistance for the high conversions and enantiocontrol.

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A highly enantioselective construction of delta- and gamma-lactone[2,3-b]piperidine skeletons was accomplished by tandem aza-Diels-Alder reaction-hemiacetal formation-oxidation from N-Tos-1-aza-1,3-butadienes and aliphatic dialdehydes.