Proline asymmetric reduction

Asymmetric reduction of the double bond of the dehydroamino acid residue in 522 can be effected in different ways since the peptide moiety can act as a chiral auxiliary. Heterogeneous hydrogenations using a Pd/C catalyst are the most frequently used conditions. Among the different amino acids evaluated as chiral auxiliaries, proline is the auxiliary of choice and has led to the best diastereodiffer-... 

A related asymmetric reduction directed by a chiral center from a (S)-proline moiety was reported by Budzikiewcz et al. earlier 101, ... 

N. Mohr and H. Budzikiewicz 107) described another example of an asymmetric reductive amination using a (S)-proline moiety as chiral inductor. 

Asymmetric reduction of imines. Japanese chemists2 have prepared a number of chiral sodium triacyloxyborohydrides from N-acyl derivatives of natural a-amino acids. The most effective are derived from (S)-proline. A particularly useful reducing agent is 1, derived from N-benzyloxycarbonyl-(S)-proline (equation I). 

The use of chiral oxazaborolidines as catalysts for the enantioselective addition of alkynylboranes to aldehydes took place in a manner analogous to the asymmetric reduction of ketones with boranes mediated by proline-derived oxazaborolidines (Equation (127)).587 Addition of alkynylboranes to A-aziridinylimines provided a convenient method to prepare allenes from carbonyl compounds (Equation (128)).5... 

We have also examined the use of chiral bi-2-naphthol to resolve some other racemic amino alcohols. The S-diphenylpyrrolidinemethanol S-10, synthesised from S-proline is useful in the preparation of the CBS oxazaborolidine catalyst,16 widely used in catalytic asymmetric reductions. Accordingly, the corresponding R-10 enantiomer is also a valuable chiral compound. 

Reduction of C=0 and C=N Bonds. Asymmetric reductions of prochiral ketones (19) to the corresponding chiral alcohols (20) using (S)-proline-modified borohydride reagents as the reductant have been published. The borane reductions of ketones (19) employing (S)-proline as chiral mediator proceeds with enantiomeric... 

The (S)-prolinate-borane complex (5)-(22) reduces ketones to the corresponding alcohols with optical yields up to 50%. The asymmetric reduction of cyclic imines (24) with chiral sodium triacyloxyborohydride (S)-(23) was utilized to prepare optically active alkaloids (25) with optical yields up to 86% (eq 9). ... 

In 2001, Tungler and coworkers described the diastereoselective hydrogenation of N (1 methylpyrrole 2 acetyl) (S) proline methyl ester (32) using the Rh/C as cata lyst [40]. By introducing (S) proline moiety as chiral auxiliary, high asymmetric induction was obtained. When 32 was subjected to 5% Rh/C catalyst in methanol with 20 bar H2, the reduced product 33 was obtained with full conversion and 95% de. This substrate induced asymmetric reduction and was effective only to (2 pyrrolyl) acetic acid derivatives (Scheme 10.30). 

Among the various chiral reagents used for the asymmetric reduction of 7,8-difluoro-3-methyl-2//-1, 4-benzoxazine (4), a borate derivative of the cyclic amino acid (S)-proline proves to be the most effective one affording the reduction product 6 with excellent enantioselectivity (95% cc) and in 92% yield32. 

Asymmetric hydrogenation. L-Proline has been convened into a series of (S)-2-(aminomethyl)pyrrolidines, such as (S)-2-(anilinomethyl)pyrrolidine (1), d + 19.7°, obtained as shown in equation (I). The product is an efficient chiral ligand for asymmetric reduction of various ketones by lithium aluminum hydride. 

Asymmetric reduction of ketimines to sec-aminesf Of the various hydride reagents found to achieve high enantioselective reduction of ketones, the oxazaborolidine 1 of Itsuno, prepared from BH3 and (S)-(—)-2-amino-3-methyl-I,l-diphenylbutane-l-ol, derived from (S)-valine, (12,31), is the most effective in terms of asymmetric induction. Like Corey s oxazaborolidines derived from (S)-proline, 1 can also be used in catalytic amounts. The highest enantioselectivities obtain in reduction of N-phenylimines of aromatic ketones (as high as 88% ee). The enantioselectivities are lower in the case of N-t-butylimines of aryl ketones (80% ee). Reduction of N-phenylimines of prochiral dialkyl ketones with 1 results in 10-25% ees. 

In 1999 [22] and 2001 [23], Matsumura and co-workers reported the first examples of stereoselective hydrosilylation with HSiCla and (5)-proline derivatives as effective activators. These works can be considered as milestones for the asymmetric reduction of ketones and imines using HSiCla as reducing agent and paved the road to the synthesis of other related systems. Since then, considerable efforts have been devoted to the development of efficient catalysts for the reduction of carbon-nitrogen double bonds, and remarkable progress has been made. 

The A -sulfinyl 1-proline amide catalysed asymmetric reduction of Al-alkyl /3-enamino esters in toluene with HSiCl3 gave the corresponding Al-alkyl-j8-amino esters in high yields with moderate to high enantioselectivities. Water as an additive was crucial for high reactivity and enantioselectivity. ... 

Perhaps the most general method of asymmetric ketone reduction is that recently developed by Corey.P l The chiral reagents such as (84, R = H) are obtained by the reaction of diborane with an amino alcohol the most effective chiral amino alcohol appears to be (83) derived from (5)-proline. The reduction of ketones occurs generally with good enantioselectivity (80-97% e.e.), and is actually catalytic in the chiral reagent, since reduction of ketones by diborane itself is very slow. 

An unusual effect of a mixed solvent on the asymmetric reduction by sodium borohydride of chiral a-keto-amides that are derived from proline has been observed which may have important consequences for the synthesis of chiral hydroxy-acids. ... 

Molecular dynamics studies in combination with sequence analysis of twelve OYE homologues were carried out to predict the stereopreference for the asymmetric reduction of l-nitro-2-phenylpropene 32a based on the amino acid sequence and structure [73]. A proline residue in the third position of a sequence pattern motif in loop p2 should thereby lead to high S-selectivity. In contrast, moderately selective enzymes exhibit a nonpolar short-chain amino acid, and all R-selective OYE homologues were predicted to contain long polar and charged amino acids in this position (Table 18.1) [73]. 

As mentioned, Matsumura published the first asymmetric reduction of ketimines with a proline formamide activator A 1 and trichlorosilane. The yield and selectivities were only moderate, but it paved the way for further developments. They showed that it was possible to reduce imines selectively in the presence of ketones without affecting the latter. Additionally, a transition state explaining the stereoinduction was hypothesized (Figure 32.6). Transition state TS 1 is preferred over TS 2 because of the steric phenyl-phenyl repulsion of the activator and the substrate. This explains the need of aryl imines for successfid stereoinduction. 

The chiral auxiliaries anchored to the substrate, which is subjected to diastereoselective catalysis, is another factor that can control these reactions. These chiral auxiliaries should be easily removed after reduction without damaging the hydrogenated substrate. A representative example in this sense is given by Gallezot and coworkers [268], They used (-)mentoxyacetic acid and various (S)-proline derivates as chiral auxiliaries for the reduction of o-cresol and o-toluic acid on Rh/C. A successful use of proline derivates in asymmetric catalysis has also been reported by Harada and coworkers [269,270], The nature of the solvent only has a slight influence on the d.e. [271],... 

The constitution of these acids was confirmed in 1908 by Leuchs and Felser, who converted them, by reduction with hydriodic acid, into proline. Their attempt to determine whether natural oxyproline was the active form of one of the synthetical compounds by converting the natural substance into its racemic form by heating with baryta to 200° C. was unsuccessful, since complete racemisation did not occur. As, however, all compounds containing one asymmetric carbon atom to which a carboxyl group is attached are easily racemised, the result led to the conclusion that oxyproline contains two asymmetric carbon atoms. Of the four possible formulae,... 

REGIO- AND STEREO-CONTROLLED OXIDATIONS AND REDUCTIONS Table 6.2 Proline-catalyzed direct asymmetric a-aminoxylation of ketones. 

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