Chiral metal complexes hetero-Diels-Alder reaction

The first example of the use of rare earth metal complexes for asymmetric catalysis in organic solvents was reported in 1983 in chiral europium-catalyzed hetero Diels-Alder reactions. As for scandium catalysts, the first chiral catalyst was reported in 1994. Diels-Alder reactions using a chiral catalyst prepared from Sc(OTf)3, (/ )-BINOL, and an amine afforded the desired products in up to 97% ee. Following these results, many chiral rare earth metal catalysts have been developed. 

Similar transformations have been performed with Danishefsky s diene and glyoxylate esters [85] catalyzed by bis (oxazoHne)-metal complexes to afford the hetero Diels-Alder product in 70% isolated yield and up to 72% ee. Jorgensen [86,87] reported a highly enantioselective, catalytic hetero Diels-Alder reaction of ketones and similar chiral copper(II) complexes leading to enantiomeric excesses up to 99% (Scheme 31, reaction 2). They also described [88] a highly diastereo- and enantioselective catalytic hetero Diels-Alder reaction of /I, y-imsaturated a-ketoesters with electron-rich alkenes... 

The solvent-free asymmetric Hetero-Diels-Alder reaction of 14 different aldehydes with Danishefsky s diene was carried out with 0.1-0.005 mol% of chiral titanium complexes to afford dihydropyrones with up to quantitative yields and 99.8% ee. A library of chiral metal complexes was generated by combining one or two different chiral diol ligands e.g. 5 (13 different diols were applied) with titanium isopropylate (Scheme 16) [46],... 

Transition-metal complexes with salen ligands can serve as catalysts for a multitude of stereogenic reactions including Diels-Alder reactions. We recently studied the application of polyglycerol-supported salen systems 18, 19 and 20 as chiral catalysts in the hetero Diels-Alder reaction between... 

Diene complexes containing alkene or diene substituents undergo Diels Alder reactions in good yields. Hetero-Diels Alder reactions have also been reported. Chirahty transfer is observed upon reaction of chiral diene iron tricarbonyl complexes. Reaction of the chiral complex (101) with cyclopentadiene in the presence of a Lewis acid give (102) with a relatively high chirahty transfer from the metal complex (Scheme 162). 

Several Ru-based transition metal complexes catalyze the hetero Diels-Alder reaction between aldehydes, in particular benzaldehyde and Danishefsky s diene. Using the [Ru(Cp)(CHIRAPHOS)] (18) complex, a modest e.e. value of 25% is obtained (Entry 1, Scheme 10.25) [48]. This reaction is also catalyzed by irradiating the chiral complex (3) in the presence of the diene and the hetero-dienophile. The product is obtained with a good chiral induction (Entry 2, Scheme 10.25) [49, 50],... 

It has been reported that several transition metal complexes catalyze the hetero-Diels-Alder reaction between a variety of aldehydes, in particular benzaldehyde, and Danishefsky s diene (Sch. 52). With the [CpRu(CHIRAPHOS)] complex the ee is modest (25 %) (entry 1) [192]. The chiral complex VO(HFBC)2 performs better in this reaction (entry 2) [193]. In experiments directed towards the synthesis of anthra-cyclones, this complex was used in cycloadditions between anthraquinone aldehydes with silyloxy dienes. One example is shown in Sch. 53 [194]. Compared with the chiral aluminum catalyst developed earlier by Yamamoto and co-workers [195], the vanadium catalyst results in lower enantioselectivity but has advantages such as ease of preparation, high solubility, stability towards air and moisture, and selective binding to an aldehyde carbonyl oxygen in the presence of others Lewis-basic coordination sites on the substrate. 

This process (hetero Diels-Alder reaction leading to a dihydropyran system) may be also conducted in an asymmetric version application of chiral transition-metal catalysts based on BINOL, BDMAP, bisoxazolines, etc. provides adducts in very high optical purity (ee up to 99%) [1,6], In a series of papers Jurczak reported recently a highly enantioselective cycloaddition of 1-methoxy-1,3-butadiene and butyl glyoxylate catalyzed with chiral salen complexes [21],... 

Mikami and coworkers also reported the development of lanthanide bis(trif-luoromethanesulfonyl)amides (bistrifylamides) as a new type of asymmetric catalysts for the hetero-Diels-Alder reaction of Danishefsky s diene, wherein the significant effect of water as an additive is observed in increasing not only the enan-tioselectivity but also the chemical yield. Bistrifylamides can be used as effective bidentate Hgands to increase the Lewis acidity of their chiral metal complexes on account of the higher acidity of the conjugated acids than those of afiphatic and aromatic diols, which are commonly used as chiral bidentate hgands [33]. 

Stereoselective oxycarborative addition is also achieved in cycloaddition and cyclooligomeriza-tion reactions. Thus, hetero-Diels-Alder reactions of dienes and aldehydes are not only catalyzed by main group Lewis acids, but also by transition metal complexes 10°. Tris[3-(heptafluoropropyl-hydroxymethylene)-( + )-camphorato]europium [( + )-Eu(hfc)3] and similar vanadium complexes have been used as the chiral catalyst in [4 + 2] cycloadditions of various achiral and chiral dienes to aldehydes63 67-101. With achiral silyloxydienes only moderate asymmetric inductions are observed, however, with chirally modified dienes, high double diastereoselectivities are achieved. Thus, the reaction of benzaldehyde with 3-terf-butyldimethylsilyloxy-l-(/-8-phenvl-menthoxy)-l.3-butadiene (1) gives (2/ .6/ )-4-wf-bntyldimethylsilyloxy-5,6-dihydro-6-phenyl-2-[(17 ,3/ ,45 )-8-phenylmenthoxy]-2f/-pyran (2) in 95% yield with a diasteieoselectivity of 25 1 ss. After crystallization and hydrolysis with trifluoroacetic acid, optically pure (2/ )-2,3-di-hydro-2-phenyl-4-(4//)-pyranone (3) is obtained in 87% yield. 

It has been proven that the chiral Pd(II) complexes as transition metal catalysts vs Lewis acid catalysts bring a breakthrough in the frontier of catalytic asymmetric organic synthesis. Here we discussed the key issues based on asymmetric carbon-carbon bond formations anomalous six-membered ring formation, ene-type cyclization leading to five-membered rings, spiro cycliza-tion, alkaloid and quinoline synthesis, Suzuki-Miyaura coupling, and C-H bond activation/C-C bond formation by transition metallic Pd(II) catalysts. On the other hand, the carbonyl-ene reaction, hetero Diels-Alder reaction, and... 

This reaction type has been applied to several other aldehydes and dienes and can be used in the synthesis of optically pure natural and non-natural carbohydrate-type systems, such as L-glucose. Hetero-Diels-Alder cycloadditions of this type can also be catalyzed by other chirally modified transition metal complexes, such as CpRu(CH2 = CH2)L3PF6 [L2 = (S)-Chi-raphos, (-)-Diop]68, (binaphthol)TiX269 70 102, vanadium103 104, or carbohydrate-modified titanium catalysts105. 

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