Chiral metal complexes cycloaddition

Different main-group-, transition- and lanthanide-metal complexes can catalyze the cycloaddition reaction of activated aldehydes with activated and non-activated dienes. The chiral metal complexes which can catalyze these reactions include complexes which enable substrates to coordinate in a mono- or bidentate fashion. 

Over the last years, one of the most studied DCR has been the asymmetric version of the cycloaddition of nitrones with alkenes. This reaction leads to the construction of up to three contiguous asymmetric carbon centers (Scheme 4). The resulting five-membered isoxazolidine derivatives may be converted into amino alcohols, alkaloids, or p-lactams. Several chiral metal complexes have been used as catalysts for this process [13-15, 18-22]. However, the employment of iridium derivatives is very scarce. 

Chiral metal complexes, aUylic alcohol epoxidation catalysis, 394-401 Chiral naphthalene derivatives, singlet oxygen cycloaddition, 271... 

The synthesis of optically active cyclopropanes via formation of dihydro-pyrazoles by 1,3-cycloaddition and azo-extrusion has been studied since the late 1950 s. Modest success (10% ee) was achieved by cycloaddition of diazoalkanes to acrylic acid, esterified with ( —)-menthol, as studied by Walborsky s group (Impastato et al., 1959). Today, the use of chiral metal complexes as catalysts for the synthesis of chiral... 

Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

Different chiral transition- and lanthanide-metal complexes can catalyze the cycloaddition reaction of unactivated and activated aldehydes with especially activated... 

Collins and co-workers have performed studies in the area of catalytic enantioselective Diels—Alder reactions, in which ansa-metallocenes (107, Eq. 6.17) were utilized as chiral catalysts [100], The cycloadditions were typically efficient (-90% yield), but proceeded with modest stereoselectivities (26—52% ee). The group IV metal catalyst used in the asymmetric Diels—Alder reaction was the cationic zirconocene complex (ebthi)Zr(OtBu)-THF (106, Eq. 6.17). Treatment of the dimethylzirconocene [101] 106 with one equivalent of t-butanol, followed by protonation with one equivalent of HEt3N -BPh4, resulted in the formation of the requisite chiral cationic complex (107),... 

Lewis acid-catalyzed cycloaddihon is also a powerful synthehc method, and various types of cycloaddihon have been reported. In parhcular, enantioselective variants using chiral Lewis acids have been comprehensively studied some of these were used as key reactions for natural product syntheses [5]. However, they generally require one or more heteroatoms in the substrates, such as enones or enoates, to which (chiral) Lewis acids can coordinate. In conhast, in the case of transition-metal-catalyzed cycloadditions, the metals coordinate direchy to the tt-electron and activate unsaturated motifs, which means that the heteroatom(s) are unnecessary. Moreover, the direct coordinahon to the reachon site can realize highly enantioselechve reachon using chiral transihon-metal complexes. 

Beside [2+2+2] cycloaddition, [4+2] and [5+1] cycloadditions represent other approaches for the construction of six-membered ring systems. In parhcular, the intermolecular and intramolecular [4+2] cycloadditions of diene and alkyne have been extensively studied, and a variety of transition-metal complexes-including those of Fe, Ni and Rh-have been reported as efficient catalysts. The first enanh-oselective reaction was achieved with a chiral Rh complex, although the substrates were limited to dienynes with a substituent on the diene terminus [36]. Later, Shibata and coworkers developed an intramolecular and enanhoselective [4+2] cycloaddition using an Ir-BDPP (l,3-bis(diphenylphosphino)pentane) complex (Scheme 11.24) [37], where dienynes with an unsubstituted diene terminus were transformed into bicyclic cyclohexa-1,4-diene with up to 98% ee. 

A variety of strategies for effecting dipolar cycloadditions from stable, neutral precursors, including carbon-carbon bond heterolysis induced by Lewis acidic metal complexes and chiral organic catalysts ... 

With Chiral Bis(oxazoline)/metal Complexes Several research groups have developed chiral Lewis acids by using chiral 1,3-bis(oxazoline) ligands for asymmetric Diels-AIder reactions. Evans designed C2-symmetric bis(oxazoline)/Cu(II) complexes derived from chiral bis(oxa-zoline)and Cu(OTf)2, and applied them to asymmetric cycloadditions of acryloyl oxazolidinones and thiazolidine-2-thione analogues. Attractive features of this catalyst system include a clearly interpretable geometry for the catalyst-dienophile complex, which rationalizes the sense of asymmetric induction for the cycloaddition process [26] (Eq. 8A.14). 

Several asymmetric versions of cycloaddition reactions with nitrones in the presence of optically active metal complexes as Lewis-acid catalysts have been reported [15]. Because of a lack of suitable chiral catalysts, however, the asymmetric design of this reaction was found to be difficult when using a,/(-unsaturated aldehydes as substrates, because these compounds are poor substrates for metal catalysts, probably because of preferential coordination of the Lewis acid catalyst to the nitrone in the presence of monodentate carbonyl compounds. Consequently, inhibition of the catalyst occurs. 

The outstanding properties of binaphthol (BINOL) as a ligand in chiral Lewis acidic metal complexes were also demonstrated highly successfully by Mikami [108, 109] using a binol-titanium complex 2-69a. Even in the cycloaddition of methyl glyoxylate 2-66 to 1 -methoxy-1,3-butadiene 2-65 which usually shows only a low selectivity, a reasonable cis/trans-selectivity and an excellent enantioselectivity could be obtained in the presence of catalytic amounts of this complex. 

Very recently, chiral tricarbonylchromium complexes have been introduced as novel chiral auxiliaries for aza Diels-Alder reactions [192, 193]. Using the brominated imine 3-8, Kiindig s group was successful in efficiently generating enantiopure polycyclic compounds such as 3-10 by cycloaddition of 3-8 to l-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s diene), subsequent radical cyclisation of the cycloadduct 3-9 and oxidative metal removal from 3-11 (Fig. 3-3). 

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],... 

Later, Lectka et al. reported a detailed synthetic and mechanistic study of unusual [4 + 2] cycloaddition of ketene enolates and o-quinones by the bifunctional catalysis of cinchona alkaloids BQD la (or BQN lb) and Lewis adds. The undertaken investigations based on the integration of experimental and calculated data itself demonstrated a surprising cooperative LA/LB interaction on a ketene enolate. It showed that the reaction of o-quinone undergoes a mechanistic switch in which the mode of activation changes from Lewis acid (LA) complexation of the quinone to metal complexation of the chiral ketene enolate. 

Azomethine ylides are very important 1,3-dipoles, and they are usually used to react with alkenes leading to the formation of the highly substituted pyrrolidine derivatives [17]. A novel and practical process for the 1,3-dipolar cycloaddition of azomethine ylides with alkenes had been reported by j0rgensen and coworkers [18]. They proposed that a dipol-chiral base ion pair would be generated between a-imino ester-metal complex and a cinchona alkaloid, and subsequent cycloaddition with dipolarophile would take place in a stereoselective manner (Scheme 10.13). 

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