S-Prolinol

The conjugate addition to acyclic enones is summarized in Table 5. The chiral hetero-cuprate derived from (S)-prolinol or cinchonidine produced products of low enantiomeric excess on treatment with chalcone (entries 3 and 4), while the cuprate from (S)-yV-methylpro-linol gave 64% ee (entry 6). Under more dilute conditions, 88% cc was obtained (entry 5). (2[Pg.909]

The second method is based on the optically active enamine formed from (S)-prolinol methyl ether and cyclohexanone. This enamine reacts spontaneously with 2-(arylmethylcnc)propane-dioates to give, after hydrolysis, the 2- (.S )-aryl[(,S )-2-oxocyclohexyllmethyl propanedioates 4 in 35-76% yield with d.r. 94 6 > 97 361. 

Recently, Pal et al. found that (.S )-prolinol could facilitate the coupling reaction of terminal alkynes with 3-iodoflavone under palladium-copper catalysis in aqueous DMF to give 3-alkynyl substituted flavones of potential biological interest (Eq. 4.17). The coupling of iodobenzene with terminal alkynes at room temperature in water without any cosolvent was completed within 30 minutes, affording the desired product in good yield.36... 

Synthesis of 1,3,2 oxazaphospholidines 128a-c derived from (S)-prolinol 127 was based either on the thermal aminoalcoholysis of the latter with prochiral alkyl(aryl) phosphonousdiamides 51a-c or its condensation reaction with /-butylphosphonous dichloride carried out in the presence of triethylamine (Scheme 37) [68], The diastereomeric excesses of the prepared derivatives ranged from 80 to 95%. 

Tetrahydropyrrolo[l,4]oxazine 74, obtained by photoinduced electron-transfer (PET) oxidative activation of substituted prolinol, undergoes nucleophilic substitution of the OH at position C-3 with allyltrimethylsilane in the presence of TiCU (Scheme 8). The reaction was highly stereoselective and produced, after hydrolysis of the resultant amide 75, optically active a-hydroxy acid 76 together with the auxiliary (.S )-prolinol that can be effectively recycled <1998TL7153>. 

The highly nucleophilic (S)-prolinol amide enolate (164) (M = Li) was alkylated employing a range of alkyl halides. The carboxylic acids (167) were obtained in chemical yields of 78-96% and outstanding optical yields 177). 

Recently, both enantiomeric forms of callosobruchusic acid (170), a pheromone of the azuki bean weevil, Callosobruchus chinensis L., which induces the male to extrude his genital organ and to attempt copulation, were synthesized by Mori et al.178), applying Evan s alkylation method in natural product synthesis as the key step. Thus, (S)-prolinol propionamide was converted to its enolate (164) by treatment with LDA. 

Some diastereoselectivity was also observed in the reaction of (S)-prolinol with the dichloride (257) leading to the chiral organophosphorus compounds (258). 

Enantioselectire alkylation of amides. Two laboratories12 have used (S)-prolinol as the chiral auxiliary for a synthesis of chiral amides. Alkylation of the enolate of the amide 1 (prepared with LDA or f-butyllithium) proceeds with pronounced... 

The synthesis of 1 starts with the reaction of dichloro(dimethylamino)borane with the Grignard reagent from 2,5-dibromohexane, and includes a resolution with (S)-prolinol. 

Bis[l,2-bis(diphenylphosphine)ethane]-palladium(O), 34 Tributyl(iodomethyl)tin, 314 Other alkylations Dichlorodimethyltitanium, 216 Potassium fluoride, 256 (S)-Prolinol, 261... 

Zirconium(IV) isopropoxide, 352 Reductive alkylation of aromatic rings Birch reduction, 32 (S)-Prolinol, 261 of carbonyl groups Trityl perchlorate, 339 of other substrates Lithium-Ammonia, 158 Reductive cleavage (see also Reduction of epoxides)... 

Diiodomethane-Diethylzinc, 276 2-Oxazolidones, chiral, 267 8-Phenylmenthol, 243 (S)-Prolinol, 261 Simmons-Smith reagent, 275 L-Valinol, 341 Amides... 

In the same vein as the cyclic sulfate activation of diols, cyclic sulfamidates have been prepared from 1,2- and 1,3-amino alcohols for the purpose of activating the carbinol toward nucleophilic attack [85-88]. (S)-Prolinol [85], A-benzyl serine t-butyl ester [86], and 2-(2-hy-... 

Other centrally chiral amine catalysts reported for kinetic resolution of alcohols include the (S)-prolinol-derived dihydroisoindolines 12a,b (Scheme 12.4), devel-... 

In 1981, Hirao and others reported that the chiral borane-amine complex 25a, derived from (S)-prolinol and 1 equivalent of BH3 THF, enantioselec-tively reduced propiophenone to afford (R )-l -phenyl-1 -propanol (26) in 44% ee9 (Scheme 4.3h). The chiral complex 25b was even better than 25a, affording the same secondary alcohol in 60% ee. Two years after the initial disclosure, Hirao et al. uncovered a new catalyst system that improved the previous experimental conditions dramatically10 (Scheme 4.3i). When the chiral aminoalcohol 27, prepared from (S)-valine methyl ester hydrochloride and phenylmagnesium bromide, was used along with 2 equivalents of BH3 THF, the enantioselectivity of the alcohol 26 jumped to 94% ee. In addition, the reaction time was shortened to 2 hours. 

Figure 6. Predominant configurations obtained by reaction of the chiral etiolates of an amide of (S)-(—)-prolinol and its O-alkyl derivatives with ethyl iodide are shown. Final products are acid obtained by hydrolyzing the alkylated amide.

Optimum asymmetric reductions of alkynones previously had been achieved employing the chiral legand in a 2 1 ratio with LAH. Dimeric ligands were synthesized from ( 1)-ephedrine and (S)-(-)-prolinol and employed 1 1 with LAH. The results (using a 3-carbon bridge) have not been encouraging (Figure 13). 

Chiral ferrocenyl derivatives with a trimethylammonium group in the a-position are known to undergo nucleophilic substitution with complete retention of configuration [2]. Quaternization of 3 with methyl iodide followed by reaction with iV-methylethanolamine, (S)-prolinol, or (lS,2R)-ephedrine gave the corresponding (R,S)-2-iodoferrocenes 4a, 4b, and 4c in 80 — 90% yield with complete retention of configuration (Scheme 3-4). Diastereomers 4d and 4e were similarly prepared starting with (S,R)-3. 

Asymmetric ethylation of benzaldehyde was conducted in the presence of 5 mol% of the ferrocenylzinc complex 5 in toluene or hexane (Scheme 3-6). Results are listed in Table 3-1. The iodoferrocene 4a itself bearing a simple iV-methyl-aminoalcohol side chain showed poor catalytic effect (entry 1) however, by chelation with zinc metal enantioselectivity was doubled (entry 2). With (S)-prolinol derivatives 4b and 4d, 1-phenylpropanol with R configuration was formed (entries... 

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