By combining enamines, derived from aldehydes and diphenylprolinol trimethylsilyl ether (the Hayashi catalyst), with nitroethenes ((D6)benzene, 4‐Å molecular sieves, room temperature) intermediates of the corresponding catalytic Michael‐addition cycles were formed and characterized (IR, NMR, X‐ray analysis; Schemes 3–6 and Fig. 1–3). Besides cyclobutanes 2 , 1,2‐oxazine N‐oxide derivatives 3 – 6 and 8 have been identified for the first time, some of which are very stable compounds. It may not be a lack of reactivity (between the intermediate enamines and nitro olefins) that leads to failure of the catalytic reactions (Schemes 3–5) but the high stability of catalyst resting states. The central role zwitterions play in these processes is discussed (Schemes 1 and 2). 相似文献
Organocatalytic Michael addition of alkoxyacetaldehyde 1 to N‐protected 2‐nitroethene‐1‐amine 2 (Scheme 2) is a key step in the synthesis of an important antiviral agent, oseltamivir. Screening of a large array of structurally diverse acids as potential promoters led to the identification of several useful acidic additives for this reaction (Tables 1–4). Also other reaction parameters were investigated with the aim of improving the diastereoselectivity of the Michael addition, while maintaining high enantiomer purity and yield (Tables 5 and 6). 相似文献
Introduction of an L ‐amino acid as a spacer and a urea‐forming moiety in a polymer‐supported bifunctional urea–primary amine catalyst, based on (1R, 2R)‐(+)‐1,2‐diphenylethylenediamine, significantly improves the catalyst’s activity and stereoselectivity in the asymmetric addition of ketones and aldehydes to nitroolefins. Yields and enantioselectivities, unprecedented for immobilized catalysts, were obtained with such challenging donors as acetone, cyclopentanone, and α,α‐disubstituted aldehydes, which usually perform inadequately in this reaction (particularly when a secondary‐amine‐based catalyst is used). Remarkably, though in the examined catalysts the D ‐amino acids as spacers were significantly inferior to the L isomers, for the chosen configuration of the diamine (match–mismatch pairs) the size of the side chain of the amino acid hardly influenced the enantioselectivity of the catalyst. These results, combined with the reactivity profile of the catalysts with substrates bearing two electron‐withdrawing groups and the behavior of the catalysts’ analogues based on tertiary (rather than primary) amine, suggest an enamine‐involving addition mechanism and a particular ordered C? C bond‐forming transition state as being responsible for the catalytic reactions with high enantioselectivity. 相似文献
An organocatalyzed diastereo‐ and enantioselective cascade aza‐Michael/Michael addition of 2‐tosylaminoenones to unsaturated pyrazolones has been developed to afford novel chiral spiropyrazolone tetrahydroquinolines containing three contiguous stereocenters. This cascade reaction proceeded well with 2 mol % chiral bifunctional tertiary amine squaramide catalyst to give the desired products in excellent yields (up to 99 %) with excellent diastereoselectivity (up to >25:1 diastereomeric ratio) and high enantioselectivity (up to 91 % enantiomeric excess). 相似文献
(?)‐Horsfiline and (?)‐coerulescine were synthesized through three one‐pot operations in 33 and 46 % overall yield, respectively. Key to the success was the efficient use of a diarylprolinol silyl ether to catalyze the asymmetric Michael addition of nitromethane to a 2‐oxoindoline‐3‐ylidene acetaldehyde. This allowed the all‐carbon quaternary, spirocyclic carbon stereocenter to be constructed in good yield with excellent enantioselectivity. 相似文献
The one‐pot sequential synthesis of (?)‐oseltamivir has been achieved without evaporation or solvent exchange in 36 % yield over seven reactions. The key step was the asymmetric Michael reaction of pentan‐3‐yloxyacetaldehyde with (Z)‐N‐2‐nitroethenylacetamide, catalyzed by a diphenylprolinol silyl ether. The use of a bulky O‐silyl‐substituted diphenylprolinol catalyst, chlorobenzene as a solvent, and HCO2H as an acid additive, were key to produce the first Michael adduct in both excellent yield and excellent diastereo‐ and enantioselectivity. Investigation into the effect of acid demonstrated that an acid additive accelerates not only the E–Z isomerization of the enamines derived from pentan‐3‐yloxyacetaldehyde with diphenylprolinol silyl ether, but also ring opening of the cyclobutane intermediate and the addition reaction of the enamine to (Z)‐N‐2‐nitroethenylacetamide. The transition‐state model for the Michael reaction of pentan‐3‐yloxyacetaldehyde with (Z)‐N‐2‐nitroethenylacetamide was proposed by consideration of the absolute configuration of the major and minor isomers of the Michael product with the results of the Michael reaction of pentan‐3‐yloxyacetaldehyde with phenylmaleimide and naphthoquinone. 相似文献
Chiral framework : Chiral amines with pyrrolidine frameworks catalyze the enantioselective conjugate addition of a wide range of aldehydes to various vinyl sulfones and vinyl phosphonates in high yields and with enantioselectivities up to >99 % ee (see scheme). The high versatility of the Michael adducts is exemplified by various functionalizations with conservation of the optical purity.
Practical and convenient synthetic routes have been developed for the synthesis of a new class of pyrrolidinyl–camphor derivatives ( 7 a–h ). These novel compounds were screened as catalysts for the direct Michael addition of symmetrical α,α‐disubstituted aldehydes to β‐nitroalkenes. When this asymmetric transformation was catalyzed by organocatalyst 7 f , the desired Michael adducts were obtained in high chemical yields, with high to excellent stereoselectivities (up to 98:2 diastereomeric ratio (d.r.) and 99 % enantiomeric excess (ee)). The scope of the catalytic system was expanded to encompass various aldehydes and ketones as the donor sources. The synthetic application was demonstrated by the synthesis of a tetrasubstituted‐cyclohexane derivative from (S)‐citronellal, with high stereoselectivity. 相似文献
An efficient approach for the preparation of functionalized 5‐aryl‐3‐(methylsulfanyl)‐1H‐pyrazoles 2 is described. This three‐component reaction between benzaldehydes 1 , NH2NH2?H2O, and 1,1‐bis(methylsulfanyl)‐2‐nitroethene proceeds in EtOH under reflux conditions in good‐to‐excellent yields. The structures of 2 were corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 2). 相似文献
An enantioselective Michael addition of thioacetic acid (AcSH) to nitroalkenes, catalyzed by a leucine‐derived bifunctional amine? thiourea, was developed with high yields and moderate enantioselectivities. The thiourea‐ammonium salt formed in the reaction is identified as the active catalyst, and the multiple H‐bonding system is responsible for the stereocontrol. The resulting thioester products are useful intermediates for the synthesis of enantiomerically enriched S‐containing compounds. 相似文献