Enantioselectivity catalytic asymmetric nitrone reactions

The LLB type catalysts were also successfully applied in the asymmetric ni-troaldol reaction of quite unreactive a,a-difluoro aldehydes. However, catalytic asymmetric nitroaldol reaction of a broad variety of a,a-difluoro aldehydes proceeded satisfactorily when using the heterobimetallic asymmetric catalysts with modified, 6,6 -disubstituted BINOL ligands [22]. The best results were obtained with the samarium (III) complex (5 mol%) generated from 6,6 -bis[(tri-ethylsilyl)ethynyl BINOL with enantioselectivities up to 95% ee. The ( -configuration of one representative nitroaldol adduct showed that the nitronate reacted preferentially on the Si face of aldehyde in the presence of (P)-LLB (20 mol% 74% yield 55% ee). It is noteworthy that the enantiotopic face selection for a,a-difluoro aldehydes is reverse to that for nonfluorinated aldehydes. The stereoselectivity for a,a -difluoro aldehydes is identical with that of P-oxa-aldehydes, suggesting that the fluorine atoms at the a-position have a great influence on enantioface selection. 

Asymmetric Aza-Henry Reactions of Nitronates with Imines. Although the Henry reaction and its aza-analogs are powerful C-C bond-forming reactions, there are few reports of catalytic asymmetric versions of these reactions. The cir-DiPh-Box copper complexes are excellent catalysts for highly diastereo and enantioselective aza-Henry reactions of a variety of trimethyl-silylnitronates with Af-(p-methoxyphenyl)-a-imino-esters (eq 3). The use of an A-(/ -methoxyphenyl) group for protection prevents undesirable side reactions and can be easily removed. The aza-Henry reaction products can be further derivatized to the corresponding a,3-diamino acids whose syntheses have rarely been reported. 

Catalytic asymmetric 1,3-dipolar cycloaddition of a nitrone with a dipolarophile has been performed using a chiral scandium catalyst [31]. The chiral catalyst, which was effective in asymmetric Diels-Alder reactions, was readily prepared from Sc(OTf)3, (7 )-(-i-)-BINOL, and d5 -l,2,6-trimethylpiperidine. The reaction of benzylbenzylide-neamine A-oxide with 3-(2-butenoyl)-l,3-oxazolidin-2-one was performed in the presence of the chiral catalyst to yield the desired isoxazolidine in 69 % ee with perfect diastereoselectivity (endolexo = > 99 1) (Sch. 8) [31,46], It was found that reverse enantioselectivity was observed when a chiral Yb catalyst, prepared from Yb(OTf)3, the same (i )-(-i-)-BINOL, and cd-l,2,6-trimethylpiperidine, was used instead of the Sc catalyst under the same reaction conditions. 

Some new combinations of chiral ligands with different Lewis acids have been lately evaluated in catalytic asymmetric 1,3-DC reactions of nitrones. When the complex derived from copper(II) triflate and bis(oxazoline) 72 was used as chiral catalyst in the cycloaddition of nitrone 66 and crotonate 68, both endo and exo isomers were obtained with very high enantioselectivities (7 3 dr > 99% ee). In this reaction, the presence of molecular sieves 4 A (MS) was crucial as in their absence the nitrone decomposed and almost no cycloadduct was obtained <04TL9581>. Sibi et al. found that square planar complexes derived from copper triflate and some chiral bisoxazolines favour the COZ-exo approach in the 1,3-DC of nitrone... 

The Mannich reaction and its variants have been reviewed, mainly focussing on asymmetric catalysis thereof. Catalytic, enantioselective, vinylogous Mannich reactions have also been reviewed, covering both direct and silyl dienolate methods. Another review surveys Mannich-type reactions of nitrones, oximes, and hydrazones. A pyrrolidine-thiourea-tertiary amine catalyses asymmetric Mannich reaction of N-Boc-imines (e.g. Ph-Ch=N-Boc) with ethyl-4-chloro-3-oxobutanoate to give highly functionalized product (16). Addition of triethylamine leads to one-pot intramolecular cyclization to give an 0-ethyl tetronic acid derivative (17). ... 

Very recently, Maruoka reported an alternative catalytic asymmetric [3 + 2] cycloaddition reaction between various nitrones and acrolein catalyzed by the x-oxo-type chiral bis-Ti(IV) oxide, giving rise to the corresponding isoxazolidine derivatives in good yields and high enantioselectivities [177]. This type of titanium Lewis acid has also been used in enantioselective 1,3-dipolar cycloaddition of diazoacetates to various substituted acroleins, affording 2-pyrazolines with a chiral quarternary carbon center (Scheme 14.78) [178]. The products obtained with these methodologies have been applied to the synthesis of natural product and biologically important molecules. 

Several successful chiral catalysts have been reported so far for catalytic asymmetric 1,3-dipolar cycloaddition reactions of nitrones with oxazolidinone derivatives (Figure 16.3) [27a,b,c] Recently, Kiindig et al. [27] had reported that the single coordination site Fe and Ru transition-metal Lewis acids can efficiently promote enantioselective 1,3-dipolar cycloadditions of nitrones with a,p-unsaturated aldehydes and represent a rapid access to substrates of high synthetic potential. The Fe catalyst (81) was found to be an excellent catalyst for 1,3-dipolar cycloaddition reactions between methacrolein and nitrone (83) (Scheme 16.24, Table 16.5). Isox-azolidine (84a) was formed as a single region- and diastereoisomer in excellent... 

In addition to this, asymmetric 1,3-dipolar cyclization reactions of nitrones with olefins,40 41 catalytic enantioselective cyanation of aldehydes,42 catalytic enantioselective animation,43 and aza-Michael reactions44 have been reported, and high enantioselectivities are observed. 

The development and application of catalytic enantioselective 1,3-dipolar cycloadditions is a relatively new area. Compared to the broad application of asymmetric catalysis in carbo- and hetero-Diels-Alder reactions (337,338), which has evolved since the mid-1980s, the use of enantioselective metal catalysts in asymmetric 1,3-dipolar cycloadditions remained almost unexplored until 1993 (5). In particular, the asymmetric metal-catalyzed reactions of nitrones with alkenes has received considerable attention during the past 5 years. 

As an alternative, iridium complexes show exciting catalytic activities in various organic transformations for C-C bond formation. Iridium complexes have been known to be effective catalysts for hydrogenation [1—5] and hydrogen transfers [6-27], including in enantioselective synthesis [28-47]. The catalytic activity of iridium complexes also covers a wide range for dehydrogenation [48-54], metathesis [55], hydroamination [56-61], hydrosilylation [62], and hydroalkoxylation reactions [63] and has been employed in alkyne-alkyne and alkyne - alkene cyclizations and allylic substitution reactions [64-114]. In addition, Ir-catalyzed asymmetric 1,3-dipolar cycloaddition of a,P-unsaturated nitriles with nitrone was reported [115]. 

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