N sulfonated imine

M. Shi and Y.-L. Shi reported the synthesis and application of new bifunctional axially chiral (thio) urea-phosphine organocatalysts in the asymmetric aza-Morita-Baylis-Hillman (MBH) reaction [176, 177] of N-sulfonated imines with methyl vinyl ketone (MVK), phenyl vinyl ketone (PVK), ethyl vinyl ketone (EVK) or acrolein [316]. The design of the catalyst structure is based on axially chiral BINOL-derived phosphines [317, 318] that have already been successfully utilized as bifunctional catalysts in asymmetric aza-MBH reactions. The formal replacement of the hydrogen-bonding phenol group with a (thio)urea functionality led to catalysts 166-168 (Figure 6.51). 

Scheme 6.159 Representative products obtained from the 166-catalyzed asymmetric aza-MBH reaction between N-sulfonated imines a,(i-unsaturated ketones and acrolein.

Bifunctional catalysis, using a phenolic BINAP-phosphine, is proposed in the enan-tioselective aza-BH reaction of N-sulfonated imines with cycloalk-2-en-l-ones.176... 

Shi, M., Chen, L.-H. Chiral phosphine Lewis base catalyzed asymmetric aza-Baylis-Hillman reaction of N-sulfonated imines with methyl vinyl ketone and phenyl acrylate. Chem. Commun. 2003,1310-1311. 

Tablel3.1 The scope of asymmetric aza MBH reaction of N sulfonated imine with MVK catalyzed by [3 ICD.

Table 13.8 Asymmetric aza MBH reaction of N sulfonated imines with MVK, phenyl vinyl ketone,...

Typical Procedures for 25a and Benzoic Acid-Catalyzed Aza-MBH Reaction of N-Sulfonated Imine with MVK [34]... 

Meng, X., Huang, Y., Chen, R. (2008). A novel selective aza-Morita-Bayhs-HiUman (aza-MBH) domino reaction and aza-MBH reaction of N-sulfonated imines with acrolein catalyzed by a bifunctional phosphine organocatalyst. Chemistry - A European Journal, 14, 6852-6856. 

Furthermore, two recent reports were published concerning bifunctional chiral phosphine catalysts 69 and 70. In both cases, N-sulfonated imines and methyl vinyl ketone in the presence of either catalyst afforded the (5)-adducts 68b,c and 71-73 in high yields with excellent enantioselectivities. 

This phase-transfer-catalyzed asymmetric Strecker reaction is further elaborated by the use of a-amido sulfone as a precursor of N-arylsulfonyl imine. In this system, the reaction can be conducted with a slight excess of potassium cyanide (1.05 equiv.), and the reaction leads to completion within 2h (Table 5.15) [46b],... 

Another catalytic application of chiral ketene enolates to [4 + 2]-type cydizations was the discovery of their use in the diastereoselective and enantioselective syntheses of disubstituted thiazinone. Nelson and coworkers described the cyclocondensations of acid chlorides and a-amido sulfones as effective surrogates for asymmetric Mannich addition reactions in the presence of catalytic system composed of O-TM S quinine lc or O-TMS quinidine Id (20mol%), LiC104, and DIPEA. These reactions provided chiral Mannich adducts masked as cis-4,5 -disubstituted thiazinone heterocycles S. It was noteworthy that the in situ formation of enolizable N-thioacyl imine electrophiles, which could be trapped by the nucleophilic ketene enolates, was crucial to the success of this reaction. As summarized in Table 10.2, the cinchona-catalyzed ketene-N-thioacyl-imine cycloadditions were generally effective for a variety of alkyl-substituted ketenes and aliphatic imine electrophiles (>95%ee, >95%cis trans) [12]. 

Herrera and Bernard have developed a new catalyhc enantioselechve approach to the asymmetric nucleophilic addition of nitromethane to N-carbamoyl imines generated from a-amido sulfones (aza-Henry reachon) [64]. The chiral phase-hansfer catalyst 85a acts in a dual fashion, first promohng the formation of the imine under mild reachon condihons and then achvahng the nucleophile for asymmetric addihon. This new strategy for the catalyhc aza-Henry reaction was... 

Alternatively, it is also possible to use in situ generated N Boc imines as electro philes [117]. When a carbamoyl sulfones are treated under the rhodium catalyzed addition of arylboronic acids, the imine is formed in situ, and the nucleophilic addition proceeds smoothly to generate the N Boc protected amine (Scheme 1.34). 

Enantioselective hydrogenation of imines in aqueous systems generated much research interest, partly because of the practical value of the product amines, partly due to the unusual kinetic observations. Imines, such as N-benzylacetophenone-imine, are relatively stable to hydrolysis, and could be reduced either in a water/ ethyl acetate two-phase solvent mixture [93, 130, 131], or in a benzene-AOT-water reverse micellar solution (AOT = bis(2-ethylhexyl)sulfosuccinate). With catalysts, prepared from [Rh(cod)Cl]2 and the products of the stepwise sulfonation of... 

Nelson and co-workers reported cinchona alkaloid-catalyzed [4-1-2] cycloaddition of ketenes and N-thioacyl imine, affording the 4,5-cw-disubstituted l,3-thiazin-6-one derivatives 146 with high enantioselectivities (>95% ee) and diastereoselectivities (>95 5 cis. trans). Scheme 3.47 [63], Ketene, in situ generated from acyl halide 143 and base, followed by addition to imine which was generated in situ via basic elimination of a-amido sulfone 144, providing the ketene-imine addition pathway toward the cycloadducts. 

Scheme 6.13 The in situ generation of N-Boc imines from a-carbamoyl sulfone derivatives followed by their enantioseiective arylation with arylboronic acids, as described by Ellman s group [18b].

Substrate control is another approach for synthesis of anti-Mannich products. The proline-catalyzed Mannich reaction between aldehydes and pre-formed N-Boc-imines affords the syn-Mannich product with exceptionally high diastereoselectivi-ties and enantioselectivities [44]. In contrast, the reaction of aldehyde 83 with N-Boc-imines, generated in situ from the stable a-amido sulfone 84, catalyzed by the commercially available chiral secondary amine 85 provides antt-Mannich product 86 with 96% ee (Scheme 28.7a) [45]. Cyclic iminoglyoxylate 88, readily prepared from commercially available starting materials, is a useful alternative imine electrophile its configuration is locked in the (Z)-form. Because of the (Z)-configuration of imine 88, the anti-selective Mannich reaction proceeds (Scheme 28.7b) [46]. 

Three different highly enantioselective addition reactions of sulfones to in situ generated N-Boc and N-Cbz imines have been reported recently, all rmder PTC using structurally similar chiral ammonium salts as catalysts (Scheme 29.31). In 2007, Shibata, Toru, and coworkers developed a PTC reaction of imines, generated in situ from a-amido sulfones, with l-fluorobis(phenyIsulfonyl)methane (FBSM) [67]. A quinidine derived quaternary ammonium chloride (52) is used as catalyst, and the Mannich-type reaction proceeds smoothly to afford the 1-fluorobis(phenylsulfonyl)methylated amines in high yields and excellent enantioselectivities. Desulfonation of adducts by treatment with Mg in EtOH yields the monofluoromethylated adducts 55 with nearly complete retention of the enantiomeric excess [Scheme 29.31 (1)]. 

Shi and coworkers almost simultaneously demonstrated the similar asymmetric aza-MBH reaction of N-protected imines 78 or N-protected a-amidoalkyl phenyl sulfones 80 with MVK catalyzed by 3-ICD or catalyst 81, affording highly enanti-oselective aza-MB H products in good yields with high enantioselectivities (Scheme 31,25) [34], Besides mild reaction conditions and operational simplicity since it avoided the handing of unstable preformed imines, the reaction was found to be general with respect to various N-protected imines. Subsequently, Shi s group reported a [3-ICD-catalyzed asymmetric MBH reaction of isatin derivatives 83 with... 

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