Aminoalcohol catalyst

Fig. 7.4. Tricyclic transition structures for aminoalcohol catalysts syn and anti refer to the relationship between the transferring group and the bidentate ligand cis and trans refer to the relationship between the aldehyde substituent and the coordinating zinc. Reproduced from J. Am. Chem. Soc., 125, 5130 (2003), by permission of the American Chemical Society.

A number of groups have reported the preparation and in situ application of several types of dendrimers with chiral auxiliaries at their periphery in asymmetric catalysis. These chiral dendrimer ligands can be subdivided into three different classes based on the specific position of the chiral auxiliary in the dendrimer structure. The chiral positions may be located at, (1) the periphery, (2) the dendritic core (in the case of a dendron), or (3) throughout the structure. An example of the first class was reported by Meijer et al. [22] who prepared different generations of polypropylene imine) dendrimers which were substituted at the periphery of the dendrimer with chiral aminoalcohols. These surface functionalities act as chiral ligand sites from which chiral alkylzinc aminoalcoholate catalysts can be generated in situ at the dendrimer periphery. These dendrimer systems were tested as catalyst precursors in the catalytic 1,2-addition of diethylzinc to benzaldehyde (see e.g. 13, Scheme 14). 

In separate experiments, the catalytic reaction was found to be first order in enantiomerically pure (i-aminoalcohol catalyst precursor, zero-order in di-ethylzinc and zero-order in aldehyde above 0.3 M. When racemic catalyst was employed, however, the overall turnover rate was six times slower, and there was a dependency of rate on the concentrations of all three species. This was elaborated further in a quantitative analysis of positive non-linearity, which is one of the classic examples of this effect. 

Oguni has reported asymmetric amplification [12] ((-i-)-NLE) in an asymmetric carbonyl addition reaction of dialkylzinc reagents catalyzed by chiral ami-noalcohols such as l-piperidino-3,3-dimethyl-2-butanol (PDB) (Eq. (7.1)) [13]. Noyori et al. have reported a highly efficient aminoalcohol catalyst, 2S)-3-exo-(dimethylamino)isobomeol (DAIB) [14] and a beautiful investigation of asymmetric amplification in view of the stability and lower catalytic activity of the het-ero-chiral dimer of the zinc aminoalcohol catalyst than the homo-chiral dimer (Fig. 7-5). We have reported a positive non-linear effect in a carbonyl-ene reaction [15] with glyoxylate catalyzed by binaphthol (binol)-derived chiral titanium complex (Eq. (7.2)) [10]. Bolm has also reported (-i-)-NLE in the 1,4-addition reaction of dialkylzinc by the catalysis of nickel complex with pyridyl alcohols [16]. 

Lattanzi et al. expanded the substrate scope to the less-reactive (3-keto-amides. Unmodified quinine and dihydroquinine were slightly more efficient than several other p-aminoalcohol catalysts, including quaternised alkaloid and thiourea derivatives (Scheme 15.23). ° However, acyclic p-ketoamides did not afford products under the same conditions. 

FIGURE 14.3. Different aminoalcohol catalysts employed in the sulfa-Michael additions. 

Scheme 15.44. Decoration of PAMAM-derivatized silica with a chiral aminoalcohol catalyst.

Aspects of the scale-up of aminoalcohol-catalyzed organozinc reactions with aldehydes have been investigated using A lV-diethylnorephedrine as a catalyst.153 In addition to examples with aromatic aldehydes, 3-hexanol was prepared in 80% e.e. 

Lewis-Acid Catalyzed. Recently, various Lewis acids have been examined as catalyst for the aldol reaction. In the presence of complexes of zinc with aminoesters or aminoalcohols, the dehydration can be avoided and the aldol addition becomes essentially quantitative (Eq. 8.97).245 A microporous coordination polymer obtained by treating anthracene- is (resorcinol) with La(0/Pr)3 possesses catalytic activity for ketone enolization and aldol reactions in pure water at neutral pH.246 The La network is stable against hydrolysis and maintains microporosity and reversible substrate binding that mimicked an enzyme. Zn complexes of proline, lysine, and arginine were found to be efficient catalysts for the aldol addition of p-nitrobenzaldehyde and acetone in an aqueous medium to give quantitative yields and the enantiomeric excesses were up to 56% with 5 mol% of the catalysts at room temperature.247... 

Recently, a novel process for the preparation of chromia promoted skeletal copper catalysts was reported by Ma and Wainwright (8), in which Al was selectively leached from CuA12 alloy particles using 6.1 M NaOH solutions containing different concentrations of sodium chromate. The catalysts had very high surface areas and were very stable in highly concentrated NaOH solutions at temperatures up to 400 K (8, 9). They thus have potential for use in the liquid phase dehydrogenation of aminoalcohols to aminocarboxylic acid salts. 

The latter effect has been demonstrated by Meijer et al., who attached chiral aminoalcohols to the peripheral NH2-groups of polypropylene imine) dendrimers of different generations [100]. In the enantioselective addition of diethyl-zinc to benzaldehyde (mediated by these aminoalcohol appendages) both the yields and the enantioselectivities decreased with increasing size of the dendrimer (Fig. 28). The catalyst obtained from the 5th-generation dendrimer carrying 64 aminoalcohol groups at its periphery showed almost no preference for one enantiomer over the other. This behavior coincides with the absence of measurable optical rotation as mentioned in Sect. 3 above. The loss of activity and selectivity was ascribed to multiple interactions on the surface which were... 

Carpentier and coworkers studied the asymmetric transfer hydrogenation of /f-keloeslers using chiral ruthenium complexes prepared from [(// -p-cyrriene)-RuC12]2 and chiral aminoalcohols based on norephedrine. During this study, these authors became aware of substrate inhibition when ketoesters carrying 4-halo-substituents were used. It transpired that this was caused by formation of a complex between the substrate and the catalyst [28]. 

Table 11.7 Comparison of rigid aminoalcohols and catalyst types (B-methyl vs. B-H).

The B-methyl catalysts were prepared by reacting the aminoalcohol with trimethyl-boroxine, followed by an azeotropic distillation with toluene. 

Catalyst Additive Time (h) Yield [%f Ee [%] Confign. of P- aminoalcohol... 

Nitroalkanols are intermediate compounds that are used extensively in many important syntheses 142). They can be converted by hydrogenation into / -aminoalcohols, which are intermediates for pharmacologically important chemicals such as chloroamphenicol and ephedrine. They are obtained by Henry s reaction by the condensation of nitroalkanes with aldehydes. The classical method for this transformation involves the use of bases such as alkali metal hydroxides, alkoxides, Ba(OH)2, amines, etc. 142-144). However, these catalysts give predominantly dehydrated products—nitroalkenes— which are susceptible to polymerization (Scheme 16). The reaction proceeds by the nucleophilic addition of the carbanion formed by the abstraction of a proton from the nitro compound to the carbon atom of the carbonyl group, finally forming the nitroaldol by abstraction of a proton from the catalyst. 

Scheme 5.4 shows some examples of enantioselective reduction of ketones using I. Adducts of borane with several other chiral /i-aminoalcohols are being explored as chiral catalyst for reduction of ketones.102 Table 5.6 shows the enantioselectivity of several of these catalysts toward acetophenone. 

In 1996, Enders and coworkers reported the asymmetric epoxidation of ( )-enones 91 in the presence of stoichiometric amounts of diethylzinc and (lR,2R)-A-methylpseudo-ephedrine (120) under an oxygen atmosphere to give fraw -epoxides 92 with excellent yields (94-99%), almost complete diastereoselectivity (>98% de) and with very good enantioselectivities (61-92%) (Scheme 54) . For the same reaction Pu and coworkers utilized achiral polybinaphthyl 121 as ligand (in excess) instead of the chiral aminoalcohol. For each substrate, only one diastereomer was formed, but in most cases yields were lower than observed with the Enders system. Enders catalyst shows high asymmetric induction for alkyl-substituted enones (ee 82-92%), but for substrates bearing only aromatic substituents only modest enantioselectivity was obtained (R = R = Ph ... 

The trail-blazing patent of Goto et al. ( ) for the oxidative dehydrogenation of aminoalcohols to the corresponding aminocarboxylic acid salts over Raney copper catalysts in strongly alkaline solutions was cast in terms of the general reaction... 

In recent work we have developed a modified autoclave which solves these difficulties by allowing the starting components, aminoalcohol and aqueous NaOH containing the catalyst, to be preheated separately to reaction temperature before mixing (10). Here we have made use of this modified reactor to determine rate constants for a range of alcohols with different structures. 

The chiral ligand (44) was prepared starting from the cyclic a-amino acid (S)-proline80). Recently, similar chiral catalysts and related molybdenum complexes involving optically active N-alkyl-P-aminoalcohols as stable chiral ligands and acetylacetone as a replaceable bidentate ligand, were designed for the epoxidation of allylic alcohols with alkyl hydroperoxides which could be catalyzed by such metal complexes 8,). 

Chiral aminoalcohols (45), derived from (2S, 4S)-4-hydroxyproline and (S)-proline, respectively, were found to be superior catalysts for the enantioselective 1,4-addition of arylthiols to 2-cyclohexen-l-one to yield 3-arylthiocyclohexanones (46) 82). 

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