S -2- Anilinomethyl pyrrolidine

The ee s of the obtained alcohols increase according to the increase in steric bulkiness of the alkyl substituents of prochiral ketones. Thus the reduction of t-butyl phenyl ketone occurs with 86% ee whereas reduction of acetophenone gives 51% ee. The enantioselective reduction of f-butyl phenyl ketone and a-tetralone (86 and 88% ee, respectively) are among the most selective of those reported.  

After quenching the reaction, the amino alcohol (1) is recovered in a yield of over 85% without any racemization. 

Chiral Ligand of LiAlH4 for the Enantioselective Reduction of a,p-Unsaturated Ketones. Enantioselective reductions of a,p-unsaturated ketones afford optically active ally lie alcohols which are useful intermediates in natural product synthesis. Enantioselective reduction of a,p-unsaturated ketones with LiAlH4 modified with chiral amino alcohol (1) affords optically active (S)-allylic alcohols with high ee s. When 2-cyclohexen-l-one is employed, (5)-2-cyclohexen-l-ol with 100% ee is obtained in 95% yield (eq 2). This is comparable with the results obtained using LiAlH4-chiral binaphthol and chiral 1,3,2-oxazaborolidine.  

When (5)-4-(2,6-xylidino)-3-methylamino-l-butanol (2) is used instead of (1), (/ )-2-cyclohexen- l-ol is obtained with less enantioselectivity (13% ee) (eq 3). 

Y Wakabayashi, Y Fujisawa, T. Tetrahedron Lett. 1983, 24,4123. 

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Almost diastereomerically pure (2i ,55)-l,3-diaza-2-methoxy-3-alkyl-2-phosphabicyclo[3.3.0]octanes (201a-d) were formed in the reaction of (S)-2-anilinomethyl)-pyrrolidines (197b-e) with methyl dichlorophosphite in the presence of NEt3 (Scheme 55) [86], With these ligands, high stereoselectivity (ee s up to 91%) was observed in the Pd catalyzed ally lie animation reaction [86],... 

Diastereomerically pure (2W,5.V)-l,3-diaza-2-(2-methylphenyl)-3-phenyl-2-phosphabicyclo[3.3.0]octane (.S )-202] was formed in the thermal reaction of (S)-2-(anilinomethyl)pyrrolidines (197a) with o-TolP(NMe2)2 and isolated in 27% yield after recrystallization (Scheme 56) [87], Its cyclopalladation with palladium diacetate followed by anion metathesis gave dimer (5,5)-203 (Scheme 56) [87],... 

A highly diastereoselective exchange reaction between a variety of bis(dimethy-lamino)arylphosphines and (S)-2-(anilinomethyl)pyrrolidine (197a) and its SV-aryl analogues constituted a key step in the synthesis of a series of substituted monodonor diazaphospholidine ligands, 213-220 [90, 91] (Figure 1). 

When the ketone (65) was treated with the chiral reagent produced by decomposing LiAlH with (S)-2-(anilinomethyl) pyrrolidine, the alcohol (66) obtained in 60 % yield. The optical yield could be determined as 62 % e.e. 95). 

Asymmetric reduction of ketonesLithium aluminium hydride in conjunction with this chiral ligand reduces prochiral aromatic ketones to (S)-secondary alcohols in 90-95% optical yields. Optical yields are lower (10-40% ee) in the case of alkyl aryl ketones. It is superior to (S)-2-(anilinomethyl)pyrrolidine for this reduction. Evidently the two methyl groups enhance the enantioselectivity. 

The asymmetric reduction of lactone (9) to give predominantly one atropoisomer can be achieved using 10 equiv of a complex prepared from LAH and BINAL (1 1) at —40°C. This reduction gives an 88 12ratio of (10a) (10b) in good yield (80%). Reduction of the same substrate with 8 equiv of a complex of LAH with (S)-(+)-2-(anilinomethyl)pyrrolidine in ether at —40°C leads to opposite stereochemical results (38 62 ratio of 10a 10b). 

S)-2-(Anilinomethyl)pyrrolidine, 458 Ansapeptides, 336-337 Anthemol, 186 Anthracydinones, 238, 260 Anthragallols, 384 Anthraquinones, 44,313 Anticapsin, 99... 

The general procedure to obtain perhydropyrrolo[l, 2-c]iraidazoles (121) is based on condensation between (S)-2-(anilinomethyl)pyrrolidine (120) and the corresponding aldehyde (Scheme 23) <82TL4953, 83CL93, 84BSF(2)77, 91BCJ2739). 

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. 

The latter compound is the amino alcohol analogue of the diamine (S)-2-(anilinomethyl)pyrrolidine (Scheme 3.1, Section 3.2.1). Not surprisingly, pro-linol has also been used to prepare bicyclic P-stereogenic oxazaphospholidines and derivatives thereof. As anticipated, their preparative methods are the same as those described in the preceding sections (Scheme 3.21). 

The diamine (99) was prepared from (S)-proline90b) or (S)-glutamic acid I15) maintaining the asymmetric center. Racemic 2-(anilinomethyl)pyrrolidine, prepared from (RS)-5-oxopyrrolidine-2-carboxylic acid, was effectively resolved into a pair of enantiomers by fractional crystallization of its mandelic acid salt U6). Moreover, the preferential crystallization of its 4-hydrobenzoic acid salt was found to produce both enantiomers in high optical purities by alternate seeding116). 

Asymmetric Michael addition. This pyrrolidine is an efficient catalyst for asymmetric Michael addition of thiols to cyclohexenone (cf. 8, 431). (S)-2-(Anilinomethyl)-1-ethylpyrrolidine, which lacks the 4-hydroxyl group of 1, has little effect on enantioselection. The important role of a hydroxyl group in several asymmetric inductions has already been noted. 

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