The Michael reaction is generally regarded as one of the most efficient, atom-economical and powerful carboncarbon bond-forming reactions in organic chemistry.[1] The development of organocatalytic asymmetric Michael reactions has been a significant research focus for several years.[2] The direct asymmetric Michael addition of carbonyl compounds with nitroalkenes to produce enantiomerically enriched nitroalkanes has been described. [3,4] Among these reactions, the Michael addition of unmodified aldehydes to nitroalkenes is of particular interest because of the valuable synthetic intermediates that are generated.[4] Betancort and Barbas originally reported the organocatalytic asymmetric Michael addition of unmodified aldehydes to nitroalkenes with moderate to good enantioselectivities.[4a] Recently 3,3'-bimorpholine derivatives, [4b] a chiral primary amine/thiourea catalyst [4c] and l-prolinol [4d] organocatalysts have been developed for the Michael addition of aldehydes to nitroolefins. Highly diastereo-and enantioselective conjugate additions that involve aldehydes were independently reported by the research groups of Wang, [4e] Hayashi, [4f] and Palomo [4g] using pyrrolidine sulfonamide (1), diphenylprolinol silyl ether (2) and trans-4-hydroxyprolylamide (3) respectively. However, some of these reactions required a large excess of donor source (up to 10 equiv of aldehyde) and high catalyst loadings (between 10 and 20 mol %). Despite the excellent results achieved from previous studies, the development of an efficient organocatalyst for direct asymmetric Michael addition of aldehydes to various aryl-and alkylnitroalkenes with low catalyst loading remains challenging in asymmetric synthesis.The metal-free, small, privileged organic molecules that catalyze enantioselective reactions have attracted much attention in recent years. Organocatalysts are usually highly efficient and selective, stable under aerobic and aqueous reaction conditions, nontoxic, environmentally friendly, and thus highly desirable as catalysts/catalytic systems. [5,6] In light of this, we have recently developed a series of camphor-based pyrrolidinyl organocatalysts that have proven their efficacy as catalysts in asymmetric synthesis. [7] In continuation of our research interest in organocatalysis, we designed and synthesized a new prolinamide-camphor organocatalysts and have shown it to be efficient catalysts for direct asymmetric Michael reaction. Herein, we wish to report an excellent diastereo-and enantioselective direct Michael addition of aldehydes with nitroalkenes catalyzed by bifunctional organocatalysts 4 a-c. The desired Michael products were obtained with high chemical yields (up to 94 %) and excellent stereoselectivities (up to 99:1 d.r. and > 99 % ee) with 5 mol % of organocatalyst 4 b.In asymmetric organocatalysis there is a strong demand for the design and synthesis of highly stereoselective, readily accessible, and tunable catalysts. The synthesis of novel prolinamide-camphor organocatalysts 4 a-c begins with the Boc-pr...

No abstract

An interesting organocatalytic reaction between 2-arylideneindane-1,3-diones and aldehydes has been developed that gives fully substituted cyclohexanes that bear two all-carbon quaternary centers. The dispirocyclohexanes were obtained in reasonable-to-good chemical yields and with high stereoselectivities (>95:5 d.r. and up to 99% ee) using a catalytic amount of commercially available α,α-l-diphenylprolinol trimethylsilyl ether (5 mol %) and DABCO (20 mol %) in DMF at -20 °C. The reaction proceeds through a unique Michael/Michael/aldol reaction that requires 2 equiv of the 2-arylideneindane-1,3-dione.

Remarkable reaction rate and excellent enantioselective direct α‐amination of unmodified aldehydes with various azodicarboxylates was catalyzed by pyrrolidinylcamphor organocatalyst 2a (5 mol‐%) to provide the desired aminated products with excellent chemical yields and high to excellent levels of enantioselectivity (up to >99 % ee) at 0 °C in CH2Cl2.