[110529-22-1]  · C18H21NO  · (S)-Diphenyl(1-methylpyrrolidin-2-yl)methanol  · (MW 267.40)

(chiral ligand for the enantioselective addition of dialkylzincs,2 alkynylzinc,3b and cyanomethylzinc bromide4 to aldehydes; chiral ligand for the enantioselective Reformatsky reaction;5 chiral ligand for the enantioselective Diels-Alder reaction;6 chiral auxiliary for asymmetric polymerization7)

Alternate Name: DPMPM.

Physical Data: mp 68.5-68.9 °C; [a]23D + 57.0° (c 1.0, CHCl3).

Solubility: sol hexane, benzene, toluene, Et2O, cyclohexane, dichloromethane.

Form Supplied in: colorless crystals; available in either enantiomeric form.

Preparative Method: reaction of Phenylmagnesium Bromide with (S)-N-[(benzyloxy)carbonyl]proline methyl ester and subsequent reduction with Lithium Aluminum Hydride affords the title compound in 83% overall yield.2b

Catalytic Enantioselective Addition of Dialkylzincs to Aldehydes.

DPMPM (1) is a chiral amino alcohol which is a precursor to a chiral catalyst for the enantioselective addition of dialkylzincs to aldehydes.2 In the presence of 2 mol % of (S)-(1), optically active alcohols of up to 100% ee are obtained from the enantioselective addition of dialkylzincs to aldehydes (eq 1, Table 1). When benzaldehyde is allowed to react with Diethylzinc using (S)-(1) (2 mol %), (S)-1-phenylpropan-1-ol with 97% ee is obtained in quantitative yield (entry 1). When the lithium alkoxide of (S)-(1) (5 mol %) is employed as a chiral ligand in the addition to aromatic aldehydes, ee's of the alcohols obtained increase to 99.5-100% ee (entries 4 and 5). Amino alcohol (1) is also effective in the enantioselective addition of Et2Zn to the aliphatic aldehyde heptanal, and (S)-nonan-3-ol with 91% ee is obtained (entry 2). In the addition to aromatic aldehydes, enantioselectivities using DPMPM are comparable with those obtained with 3-exo-(dimethylamino)isoborneol (DAIB).8 In the addition to heptanal, DPMPM (1) is more enantioselective than DAIB (61% ee). However, in the addition to aliphatic aldehydes of wider range, N,N-dibutylnorephedrine9 is more enantioselective than (1).

The sense of the asymmetric induction is dependent on the structure of the catalyst. (1R,2S)-Phenyl(1-neopentylpyrrolidin-2-yl)methanol (2) mediates the addition of Et2Zn to aldehydes to afford (R)-alcohols in up to 100% ee (entry 3).2b By using (1) as a chiral ligand, optically active fluorine-containing alcohols10 and deuterio alcohols11 of high optical purities have been synthesized (entries 6 and 7). The enantioselective addition to a,b-unsaturated aldehydes (e.g. cinnamaldehyde) using (1) affords optically active allylic alcohols with 89-97% ee (entries 8 and 9).2 Enantioselective addition of dialkylzincs to alkynyl aldehydes and furyl aldehydes using (1) as a chiral catalyst affords optically active alkynyl alcohols (78% ee, entry 10)3 and furyl alcohols (88-94% ee).12 When terephthalaldehyde is allowed to react with Et2Zn using (1) as a chiral ligand, the corresponding optically pure diol is obtained.13

Unlike alkyllithium and Grignard reagents, dialkylzinc does not add to ketones even in the presence of (1). Thus the chemo- and enantioselective alkylation of a keto aldehyde (4-benzoylbenzaldehyde) with Et2Zn using (S)-(1) affords the corresponding optically active hydroxy ketone with 93% ee in 99% yield.14

Enantioselective Addition of Cyanomethylzinc Bromide, Reformatsky Reagent, and Alkynylzinc Reagents to Aldehydes.

The enantioselective additions of cyanomethylzinc bromide,4 Reformatsky reagent (see Ethyl Bromozincacetate),5 and alkynylzinc3b reagent to aldehydes using (1) as chiral catalyst or ligand afford optically active b-hydroxy nitrile (93% ee),4 b-hydroxy ester (78% ee) (eq 2),5 and alkynyl alcohol (43% ee).3b

Catalytic Asymmetric Diels-Alder Reaction.

Amino alcohol (1) combined with Boron Tribromide generates a chiral catalyst for the asymmetric Diels-Alder reaction (97% ee) of unsaturated aldehydes and dienes.6

Asymmetric Polymerization.

Polymerization of methacrylate derived from (1) affords optically active polymer of helical conformation of single screw sense.7

1. (a) Soai, K.; Niwa, S. CRV 1992, 92, 833. (b) Noyori, R.; Kitamura, M. AG(E) 1991, 30, 49.
2. (a) Soai, K.; Ookawa, A.; Ogawa, K.; Kaba, T. CC 1987, 467. (b) Soai, K.; Ookawa, A.; Kaba, T.; Ogawa, K. JACS 1987, 109, 7111.
3. (a) Soai, K.; Niwa, S. CL 1989, 481. (b) Niwa, S.; Soai, K. JCS(P1) 1990, 937.
4. Soai, K.; Hirose, Y.; Sakata, S. TA 1992, 3, 677.
5. Soai, K.; Kawase, Y. TA 1991, 2, 781.
6. Kobayashi, S.; Murakami, M.; Harada, T.; Mukaiyama, T. CL 1991, 1341.
7. Okamoto, Y.; Nakano, T.; Ono, E.; Hatada, K. CL 1991, 525.
8. Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. JACS 1986, 108, 6071.
9. (a) Soai, K.; Yokoyama, S.; Ebihara, K.; Hayasaka, T. CC 1987, 1690. (b) Soai, K.; Yokoyama, S.; Hayasaka, T. JOC 1991, 56, 4264.
10. Soai, K.; Hirose, Y.; Niwa, S. JFC 1992, 59, 5.
11. Soai, K.; Hirose, Y.; Sakata, S. BCJ 1992, 65, 1734.
12. (a) Soai, K.; Kawase, Y.; Niwa, S. H 1989, 29, 2219. (b) Van Oeveren, A.; Menge, W.; Feringa, B. L. TL 1989, 30, 6427.
13. Soai, K.; Hori, H.; Kawahara, M. CC 1992, 106.
14. Soai, K.; Watanabe, M.; Koyano, M. CC 1989, 534.

Kenso Soai

Science University of Tokyo, Japan

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