Catalysts camphor-based

Asymmetric Diels-Alder reactions have also been achieved in the presence of poly(ethylene glycol)-supported chiral imidazohdin-4-one [113] and copper-loaded silica-grafted bis(oxazolines) [114]. Polymer-bound, camphor-based polysiloxane-fixed metal 1,3-diketonates (chirasil-metals) (37) have proven to catalyze the hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene. Best catalysts were obtained when oxovanadium(lV) and europium(III) where employed as coordinating metals. Despite excellent chemical yields the resulting pyran-4-ones were reported to be formed with only moderate stereoselectivity (Scheme 4.22). The polymeric catalysts are soluble in hexane and could be precipitated by addition of methanol. Interestingly, the polymeric oxovanadium(III)-catalysts invoke opposite enantioselectivities compared with their monomeric counterparts [115]. 

Although cobalt catalysts have been rarely used in cyclopropanation reactions, Nakamura and coworkers2 1 have developed the camphor-based complex (35) as a useful asymmetric catalyst, as shown in a typical example in equation (16). High yields were obtained with dienes and styrenes but cyclopropanation did not occur with simple alkenes. Studies with cu-ife-styrene showed that, unlike other catalytic systems, the reaction was not stereospecific with respect to alkene geometry. 

A variety of methods exists for the synthesis of optically active amino acids, including asymmetric synthesis [85-93] and classic and enzymatic resolutions [94-97], However, most of these methods are not applicable to the preparation of a,a-disubstituted amino acids due to poor stereoselectivity and lower activity at the a-carbon. Attempts to resolve the racemic 2-amino-2-ethylhexanoic acid and its ester through classic resolution failed. Several approaches for the asymmetric synthesis of the amino acid were evaluated, including alkylation of 2-aminobutyric acid using a camphor-based chiral auxiliary and chiral phase-transfer catalyst. A process based on Schollkopf s asymmetric synthesis was developed (Scheme 12) [98]. Formation of piperazinone 24 through dimerization of methyl (5 )-(+)-2-aminobutyrate (25) was followed by enolization and methylation to give (35.6S)-2,5-dimethoxy-3,6-diethyl-3.6-dihydropyrazine (26) (Scheme 12). This dihydropyrazine intermediate is unstable in air and can be oxidized by oxygen to pyrazine 27, which has been isolated as a major impurity. 

Platinum complexes show none of the catalytic activity found in palladium and nickel complexes. This chemical inertness makes platinum a useful model for the more active catalysts. There has been a suggestion that platinum complexes of chiral a-diimines might lead to stereoselective olefin polymerization. Chiral camphor-based ligands have been employed in palladium complexes for ethylene polymerization, but there was no mention of stereoselectivity in hexene polymerizations. 

To end this section, it has to be mentioned that there is a single example of a conjugate Friedel Crafts alkylation involving enones as Michael acceptors. In particular, a camphor-based sulfonic acid (94) has been used as catalyst in the reaction of indoles with chalcones (Scheme 4.57). It has also to be noted that the best conditions involved the use of catalyst 94 together with an ionic liquid (l-butyl-3-methyl-l//-imidazolium bromide BmimBr). However, although excellent yields were obtained for a set of different substrates tested, the enantioselectivities remained in rather low values. 

In 2003, Rawal reported the use of TADDOLs 177 as chiral H-bonding catalysts to facilitate highly enantioselec-tive hetero-Diels-Alder reactions between dienes 181 and different aldehydes 86 (Scheme 6.29A) [82], and also BINOL-based catalysts 178 were found to facilitate this reaction with excellent selectivities [83]. TADDOLs were also successfully used as organocatalysts for other asymmetric transformations like Mukaiyama aldol reactions, nitroso aldol reactions, or Strecker reactions to mention a few examples only [84]. In addition, also BINOL derivatives have been employed as efficient chiral H-bonding activators as exemplified in the Morita-Baylis-Hilhnan reaction of enone 184 with different carbaldehydes 86 [85]. The use of chiral squaramides for asymmetric reactions dates back to 2005 when Xie et al. first used camphor-derived squaric amino alcohols as ligands in borane reductions [86]. The first truly organocatalytic application was described by Rawal et al. in 2008 who found that minute amounts of the bifunctional cinchona alkaloid-based squaramide 180 are... 

The structural motifs of some excellent chiral crown ethers have been derived from easily accessible natural products. For example, a (+)-camphor-based chiral aza-crown ether 7 was developed and successfully apphed in asymmetric conjugate addition by Brunet [11]. The use of D-glucose-based crown ethers 8 and 9 as chiral phase-transfer catalysts has been intensively studied by Bako and colleagues in the asymmetric Michael addition [12], Darzens condensation [13], and epoxidation [14]. Another carbohydrate-derived chiral crown ether 10 was prepared from chiro-inositol by Aldyama and coworkers, which successfully enabled the enantioselective conjugate addition of N-(diphenylmethylene) glycine tert-butyl ester to several electrophiles [15]. 

The first reported chiral catalysts allowing the enantioselective addition of diethylzinc to aryl aldehydes in up to 60% cc were the palladium and cobalt complexes of 1,7,7-trimethylbicy-clo[2.2.1. ]heptane-2,3-dione dioxime (A,B)3. A number of other, even more effective catalysts, based on the camphor structure (C K, Table 26) have been developed. 

In 2006, Wang et al. reported the synthesis of a new camphor-derived disulfonamide ligand based on L-tartaric acid that was employed in similar reactions to those described above, giving rise to enantioselectivities of up to 83% ee by using 5 mol% of catalyst loading (Scheme 3.43). ... 

A new chiral auxiliary based on a camphor-derived 8-lactol has been developed for the stereoselective alkylation of glycine enolate in order to give enantiomerically pure a-amino acid derivatives. As a key step for the synthesis of this useful auxiliary has served the rc-selective hydroformylation of a homoallylic alcohol employing the rhodium(I)/XANTPHOS catalyst (Scheme 11) [56]. 

However, most asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides with alkenes are carried out without Lewis acids as catalysts using either chiral alkenes or chiral auxiliary compounds (with achiral alkenes). Diverse chiral alkenes are in use, such as camphor-derived chiral N-acryloylhydrazide (195), C2-symmetric l,3-diacryloyl-2,2-dimethyl-4,5-diphenylimidazolidine, chiral 3-acryloyl-2,2-dimethyl-4-phenyloxazolidine (196, 197), sugar-based ethenyl ethers (198), acrylic esters (199, 200), C-bonded vinyl-substituted sugar (201), chirally modified vinylboronic ester derived from D-( + )-mannitol (202), (l/ )-menthyl vinyl ether (203), chiral derivatives of vinylacetic acid (204), ( )-l-ethoxy-3-fluoroalkyl-3-hydroxy-4-(4-methylphenylsulfinyl)but-1 -enes (205), enantiopure Y-oxygenated-a,P-unsaturated phenyl sulfones (206), chiral (a-oxyallyl)silanes (207), and (S )-but-3-ene-1,2-diol derivatives (208). As a chiral auxiliary, diisopropyl (i ,i )-tartrate (209, 210) has been very popular. 

Further evidence for the formation of intermediate compounds in catalytic reactions is afforded by the observation (a) that optically active camphor is formed from optically inactive (racemic) camphor carboxylic acid in the presence of the d- or /-forms of quinine, quinidine or nicotine and (6) that optically active bases, e.g., quinidine, catalyze the synthesis of optically active mandelonitrile from benzaldehyde and hydrocyanic acid.10 These results hardly admit of any other interpretation than the intermittent production of a catalyst-reactant compound. 

An asymmetric permanganate-promoted oxidative cyclization of 1,5-dienes using a chiral phase-transfer catalyst was recorded <2001AGE4496>, and a diastereoselective permanganate-mediated oxidative cyclization with an Oppolzer sultam has been employed in the total synthesis of m-solamin <20020L3715>. In a metal-oxo-mediated approach to the synthesis of 21,22-di- /)7-membrarollin based on the use of a camphor-derived Oppolzer sultam as... 

Two years later, Marko et al. reported an improved catalytic system which only required 0.25 equivalent of potassium carbonate instead of 2 equivalents (89). The oxidation reaction described above is dramatically influenced by the nature of the solvent. Thus, if the reaction was performed in fluorobenzene, total conversion of undecan-2-ol to undecan-2-one could be reached with 0.25 equivalent K2CO3, whereas 2 equivalents of base were necessary in toluene to convert 90% of this secondary aliphatic alcohol (Table VI). These optimized conditions were applied to a variety of functionalized alcohols and the results are reported in Table VII. The catalyst tolerates both sulphur and nitrogen substituents on the substrate. Indeed, (thiophen-2-yl)methanol, N-protected (S)-valinol or (S)-prolinol could be oxidized to the corresponding aldehydes with very good yields. In addition, no racemization was detected for the two P-amino alcohols as well as for (2S,5i )-2-isopropyl-5-methylcyclohexanol. The hindered endo- and exo-borneol are both converted to camphor with similar reaction rates, despite their distinctly different steric properties. 

You and co-workers successfully developed a series of novel chiral triazolium salts based on the readily available camphor scaffold in 2008. These catalysts are capable of rendering excellent enantioseleetivity in the intramolecular Stetter reaction (up to 97% yield, 97% ee). A later report from the same group delivered the synthesis of chiral NHCs from (lR,2R)-(+)-diphenyl ethylenediamine. With 10 mol% of the catalyst, the intramolecular Stetter reaction was realized in excellent yields with up to 97% ee. These newly developed catalysts from camphor and (lR,2R)-(+)-diphenyl ethylenediamine accumulate in the toolkit of NHCs. 

Asymmetric hydrosilylation can be accomplished (i) by [RhO(PPh3)3] if the organic substrate is optically active, e.g. (-)-menthane or ( + )-camphor, or (ii) if chiral phosphine-rhodium catalysts are used. In the particular case where the catalyst is a (diop)rhodium(i) derivative molecular models of intermediates based on oxidative addition of the silane to Rh, e.g. (61), can be used to predict the chirality of products... 

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