Enantioselective Mannich reactions of pyruvates catalyzed by amine-based catalyst systems, in which pyruvates act as nucleophiles, are reported. The reactions of pyruvates and cyclic sulfonylimines afforded the desired Mannich products, including those bearing tetrasubstituted carbon centers, in high yields with high enantioselectivities in most cases. The selection of the acid used in the amine-based catalyst system was key for the formation of the Mannich products with high enantioselectivities.

The decalin structure is found in bioactive molecules. We have developed catalytic enantioselective formal (4+2) cycloaddition reactions via aldol-aldol cascade reactions between pyruvate-derived diketoester derivatives and cyclohexane-1,3-dione derivatives that afford highly functionalized decalin derivatives. The reactions were performed using a quinidine-derived catalyst under mild conditions. Decalin derivatives bearing up to six chiral carbon centers including tetrasubstituted carbon centers were synthesized with high diastereo- and enantioselectivities. Five to six stereogenic centers were generated from achiral molecules with the formation of two C-C bonds in a single transformation resulting in the formation of the decalin system.

Treatment of aldehydes with sulfur ylide (CH 2 =SOMe 2 or CH 2 =SMe 2 ), in the presence of CO 2 (1 atm) bubbled sequentially under mild conditions, produces cyclic carbonates in preparative yields. Sodium iodide formed in situ promotes the reaction between epoxide as intermediate and CO 2 at ambient conditions, thus constituting a powerful metal-free synthesis of organic cyclic carbonates directly from aldehydes.Key words: cyclization, epoxides, insertion, carbon dioxide, cyclic carbonates Carbon dioxide is one of the major constituents of greenhouse gases, and to control its rapidly increased concentration in atmosphere is a major challenge for scientific communities. 1 Global-warming concern has dramatically increased interest in using CO 2 as a feedstock for the preparation of value-added chemicals. 1j Although CO 2 is an attractive nonhazardous C 1 synthon in abundance, its utilization in chemical transformations remains challenging because of its high thermodynamic stability and low chemical reactivity. 2 In particular, the synthesis of lowenergy target molecules (e.g., organic carbonates) represents a promising alternative to overcome this thermodynamics. Organic cyclic carbonates are biodegradable chemicals that find tremendous applications as electrolytic materials in lithium ion batteries, polar aprotic solvents, intermediates in the production of pharmaceuticals and fine chemicals, as well as for developing engineered polymeric materials. 3 Biologically active molecules that contain a cyclic carbonate moiety have also been isolated from various natural sources. 4 In literature, cyclic carbonates are generally prepared by the cycloaddition of CO 2 with epoxides in the presence of many activating reagents such as quaternary ammonium salts, 5a-c azaphosphatranes, 5d metal-salen complexes derived from Al, Zn, Mg, and other first-row transition metals. 6 Other methods of their synthesis include the reaction of CO 2 with styrenes, 7 propargyl alcohols, 8 allyl alcohols, 9 diols, 10 or halohydrins. 11 Although these reported methods provide a simple route for the environmentally benign chemical fixation of CO 2 to produce cyclic carbonates, these have certain limitations such as dependence on epoxides as starting materials, use of toxic or costly reagents, relatively high pressure and temperature, often requiring a tedious workup procedure for their isolation. Sulfur ylides have been widely employed in the conversion of aldehydes into epoxides (Corey-Chaykovsky reaction) in organic synthesis, thereby serving as C 1 carbon source under ambient conditions. 12 In this note, we wish to disclose an efficient and metal-free, one-pot procedure for the synthesis of organic cyclic carbonates by the sequential reaction of aldehydes with sulfur ylides (CH 2 =SOMe 2 or CH 2 =SMe 2 ) followed by its reaction with CO 2 (1 atm) in the absence of heavy-metal additives under ambient conditions (Scheme 1).Scheme 1 Synthesis of cyclic carbonates from aldehydes, sulfur ylide, and CO 2 Preliminary experiments have s...

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The employed catalyst can be reused three times without any decrease in catalytic activity.

We have developed and investigated a catalytic desymmetrization reaction strategy that affords functionalized decalin derivatives with high enantioselectivities from C2-symmetric derivatives through aldol–aldol annulation. We identified the structural moieties of the catalyst necessary for the formation of the decalin derivative with high enantioselectivity. We elucidated the mechanisms of the catalyzed reactions: the first aldol reaction step was reversible, and the second aldol step was rate-limiting and stereochemistry-determining and was enantioselective. Using theoretical calculations guided by the experimental results, we identified the interactions between the catalyst and the transition state that led to the major enantiomer. The information obtained in this study will be useful for the development of catalysts and chemical transformations.

A one step formal [3+2]-annulation protocol for the synthesis of 2,3-disubstituted indolines is described. The in situ generated aryne acts as a two-atom component, and γ-amino-α,β-unsaturated esters acting as a three-atom component to construct indoline units in a highly regio- and diastereoselective manner with yields ranging from 63 to 80%.

The decalin structure is found in bioactive molecules.W eh ave developed catalytic enantioselective formal (4+ +2) cycloaddition reactions via aldol-aldol cascade reactions between pyruvate-derived diketoester derivatives and cyclohexane-1,3-dione derivatives that affordh ighly functionalized decalin derivatives.The reactions were performed using aq uinidine-derived catalyst under mild conditions.D ecalin derivatives bearing up to six chiral carbon centers including tetrasubstituted carbon centers were synthesized with high diastereo-and enantioselectivities.F ive to six stereogenic centers were generated from achiral molecules with the formation of two C À Cb onds in as ingle transformation resulting in the formation of the decalin system. The decalin ring system is found in diterpenes,diterpenoids, steroids,a nd other bioactive natural products and related molecules ( Figure 1). [1] Decalin derivatives often have antiinflammatory,a nti-bacterial, and anti-tumor activities. [1] Therefore,s ynthesis of functionalized decalin derivatives is of interest in drug discovery efforts and in related research. [2][3][4][5] Construction of the decalin ring system has been performed using cycloadditions, [2] cross coupling, [3] polyene cyclizations and related ene-involved annulations, [4] Robinson annulations [2c,d, 5] and related Michael-aldol reactions, [6] in which the reactions start from Michael additions to a,b-unsaturated ketones.H ere we report organocatalytic enantioselective aldol-aldol annulation cascade reactions to afford functionalized decalin derivatives (Scheme 1).In our strategy,C2symmetric starting materials pyruvatederived diketoester derivatives (dihydropyran derivatives) 1 [7] and cyclohexane-1,3-diones 2 are used for the aldol-aldol annulation cascade reactions to construct new cyclohexane rings,r esulting in the formation of decalin derivatives 3 or 4 (Scheme 1). Ther eaction is expected to generate five or six stereogenic centers,d epending on the substituent of 2.W e hypothesized that appropriate catalysts and conditions would accelerate the reactions of 1 with 2 to afford decalin derivatives 3 and 4 with high diastereo-and enantioselectivities. [8] First, we searched for catalysts and conditions for the reaction of 1a and 2a to afford 3a.Selected results are shown in Table 1. Ther eaction in the presence of triethylamine afforded racemic product 3a in ag ood yield (entry 1). For enantioselective versions of the reaction, the use of (DHQD) 2 AQN [9] with tetraethylammonium bromide (TEAB) as additive in toluene-N-methyl-2-pyrrolidone (NMP) resulted in the formation of 3a in ag ood yield as as ingle diastereomer with high enantioselectivity (er 93:7, entry 4). Addition of TEAB improved the enantioselectivity (entry 2v ersus entry 3). Theu se of toluene-NMP as the solvent improved the solubility of 2a and resulted in faster reaction than the same reaction in toluene without affecting the enantioselectivity (entry 4v ersus entry 3). Theu se of three or more equivalents of 2a did not provide bette...