2-amino-1,2,2-triphenylethanol: A novel chiral reagent containing the diphenylaminomethyl group. Enantioselective addition of diethylzinc to benzaldehyde

Article abstract of DOI:10.1055/s-1998-1953

The novel chiral amino alcohols (R)- and (S)-1 are prepared from the corresponding enantiomer of ethanediol 2. Alkoxytitanium complexes of the imines 8 derived from 1 are suitable to catalyze the addition of diethylzinc to benzaldehyde in up to 92% e.e.

Full text of DOI:10.1055/s-1998-1953

December 1998
SYNLETT
1441
2-Amino-1,2,2-triphenylethanol: A Novel Chiral Reagent Containing the Diphenyl-
aminomethyl Group.
Enantioselective Addition of Diethylzinc to Benzaldehyde
Ralf Fleischer and Manfred Braun*
Institut für Organische und Makromolekulare Chemie, Universität Düsseldorf, Universitätsstraße 1, D-40225 Düsseldorf, Germany
Fax: +49 211 81 13085; E-mail: braunm@uni-duesseldorf.de
Received 22 September 1998
Abstract: The novel chiral amino alcohols (R)- and (S)-1 are prepared
from the corresponding enantiomer of ethanediol 2. Alkoxytitanium
complexes of the imines 8 derived from 1 are suitable to catalyze the
addition of diethylzinc to benzaldehyde in up to 92% e.e.
sulfuric acid, whereas (S)-1 was prepared from (S)-oxazoline 4 by the
same protocol (Scheme 2).
9
Ph
O
a
b
S
O
(R)-2
Ph
Ph
88%
O
64%
In recent developments of asymmetric synthesis, the structural unit of
the diarylhydroxymethyl group was frequently applied, not only in
covalently bound chiral auxiliary reagents, but also in ligands and
3
1
Ph
Ph
OH
Ph
catalysts. It led to an enhancement of stereoselectivity in many cases,
O
N
c
although it is not a stereogenic group. After the application of the
Me
2
Ph
Ph
88%
diarylhydroxymethyl motif in TADDOLs and triphenylglycol-derived
NH2
Ph
3
carboxylic esters, it was also used in β-amino alcohols, most of which
(R)-4
4
(R)-1
are based on valine and proline. In this communication, we present a
new chiral auxiliary reagent, (R)- and (S)-2-amino-1,2,2-
triphenylethanol 1, which contains the diphenylaminomethyl moiety,
hitherto unexplored in asymmetric syntheses. The preparation and the
first application of the novel reagent 1 in enantioselective additions of
diethylzinc are reported.
Reagents and conditions: a) Ref. 6. b) CH3CN (1.5 ml/mmol), TfOH
(2.0 equiv.), −10°C → rt, 16 h. c) conc. H2SO4 (12% in MeOH), reflux,
10 d.
Scheme2
O
OH
R2
Ph
Ph
R1
OH
H
OH
OH
R3
NH2
Ph
NH2
NH2
(R)-5
6
Ph
Ph
OH
N
(R)-1
(S)-1
(R)-5
+
OH
R2
Ph
a
R1
H
6a,b
R3
OH
OH
OH
OH
(R)-7
Ph
Ph
OH
N
(R)-1
+
OH
R2
b
Ph
R1
(R)-2
(S)-2
H
6a−d
R3
Scheme 1
(R)-8
(R)- and (S)-triphenylglycol 2, readily available from the corresponding
R1
R2
R3
3,5
enantiomers of mandelic acid, were chosen as starting materials for
6
8a
the amino alcohols (R)- and (S)-1, respectively. As described recently,
C4H4
6a
7a
7b
H
the cyclic sulfite 3 was generated from the diol (R)-2 by treatment with
thionyl chloride in the presence of triethylamine. Although the pure
R ,S stereoisomer can be readily isolated, the diastereomeric mixture of
6b
6c
6d
8b
8c
8d
t-Bu
t-Bu
t-Bu
H
H
H
H
t-Bu
OMe
c
s
3 was used in the following step: in an unprecedented variant of the
Ritter reaction, the sulfite 3 delivered the oxazoline 4 upon treatment
with triflic acid in acetonitrile. Finally, the amino alcohol (R)-1 was
Reagents and conditions: a) Ref. 14. b) Na2SO4, MeOH/CH2Cl2,
60°C, 12−20 h (8a−c); −20°C → rt, 48 h (8d).
7,8
liberated from the oxazoline (R)-4 by methanolysis in the presence of
Scheme 3

1442
LETTERS
SYNLETT
10
The phenylglycine-derived amino alcohol 5, obviously a regioisomer
(2) Beck, A. K.; Bastani, B.; Plattner, D. A.; Petter, W.; Seebach, D.;
Braunschweiger, H.; Gysi, P.; LaVecchia, L. Chimia 1991, 45,
238. Dahinden, R.; Beck, A. K.; Seebach, D. In Encyclopedia of
Reagents for Organic Synthesis; Paquette, L. A., Ed.; Vol. 3,
Wiley: Chichester, 1995; p 2167 and references given therein.
11
of reagent 1, was used in enantioselective ketone reductions and
allylic oxidations previously. When the regioisomers 1 and 5 were
condensed with phenolic aldehydes 6, the imines 7 and 8 resulted.
12
13
Titanium complexes derived from ligands 7 were recently isolated and
characterized. In order to compare the efficiency of the regioisomeric
14
(3) Braun, M.; Devant, R. Tetrahedron Lett. 1984, 25, 5031. Braun,
M.; Gräf, S. Org. Synth. 1993, 72, 38. Braun, M.; Sacha, H. J.
Prakt. Chem. 1993, 335, 653. Braun, M.; Sacha, H.; Galle, D.;
Baskaran, S. Pure Appl. Chem. 1996, 68, 561.
chiral auxiliaries 1 and 5, titanium complexes were generated from their
imines 7 and 8 by treatment with titanium tetraisopropoxide followed by
evaporation of 2-propanol. The catalysts formed thereby were used in
15
the addition of diethylzinc to benzaldehyde, a conversion previously
(4) Itsuno, S.; Nakano, M.; Miyazaki, K.; Masuda, H.; Ito, K.; Hirao,
A.; Nakahama, S. J. Chem. Soc., Perkin Trans. I 1985, 2039.
Hayashi, M.; Miyamoto, Y.; Inoue, T.; Oguni, N. J. Org. Chem.
1993, 58, 1515. Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am.
Chem. Soc. 1987, 109, 5551. Corey, E. J.; Bakshi, R. K.; Shibata,
S.; Chen, C.-P.; Singh, V. K. J. Am. Chem. Soc. 1987, 109, 7925.
Corey, E. J.; Shibata, S.; Bakshi, R. K. J. Org. Chem. 1988, 53,
2861. Enders, D.; Bhushan, V. Tetrahedron Lett. 1988, 29, 2437.
See also ref. 15e−h.
16
not mediated by imine-alkoxytitanium complexes. The enantiomeric
1
excess of the alcohol 9 obtained thereby was determined by H NMR
17
analysis of the corresponding Mosher ester. The titanium complexes
derived from 7 and 8, respectively, were used in amounts of 10 to 20
mole percent.
Et2Zn (2.0 equiv.)
O
OH
7 or 8 (10−20 mol%)
Ti(OiPr)4 (10−20 mol%)
Ph
H
(5) Braun, M.; Gräf, S.; Herzog, S. Org. Synth. 1993, 72, 32.
Ph
Et
toluene
(R)-9
(6) Fleischer, R.; Galle, D.; Braun, M. Liebigs Ann./Recueil 1997,
1189.
Scheme 4
(7) For a Ritter reaction rendered by triflic acid, see: Senanayake, C.
H.; Larsen, R. D.; DiMichelle L. M., Liu, J.; Toma, P. H.; Ball, R.
G.; Verhoeven, T. R.; Reider, P. J. Tetrahedron: Asymmetry 1996,
7, 1501.
(8) The specific rotation of the heterocyclic compound (R)-4 was
20
measured to be [α]
= +231 (c = 1, CHCl ). In the light of this
3
D
value, a recent report on the synthesis of enantiopure (R)- and (S)-
4 seems obsolete, see: Lopez, L.; Farinola, G. M.; Paradiso, V.;
Mele, G.; Nacci, A. Tetrahedron 1997, 53, 10817.
(9) Racemic 1 was obtained by 1,3-dipolar cycloadditions of different
benzhydrylisonitrile ylides to benzaldehyde followed by cleavage
of the resulting oxazoline, see: Bittner, G.; Witte, H.; Hesse, G.
Justus Liebigs Ann. Chem. 1968, 713, 1. Uminski, M; Jawdosiuk,
M. Pol. J. Chem. 1983, 57, 67.
(10) McKenzie, A.; Wills, G. O. J. Chem. Soc. 1925, 127, 283.
(11) Berenguer, R.; Garcia, J.; Vilarrasa, J. Tetrahedron: Asymmetry,
1994, 5, 165. Prasad, K. R. K.; Joshi, N. N. Tetrahedron:
Asymmetry 1996, 7, 3147.
As shown in Table 1, only moderate enantioselectivities were obtained
with the phenylglycine-derived imines 7 (entries 1 and 2). A significant
improvement was brought about when the chiral ligands 8 formed from
the amino alcohol 1 were used (entries 3-5). Furthermore, a t-butyl
group in ortho position to the phenol residue turned out to be crucial for
enantioselectivity. A final improvement came from the introduction of a
methoxy substituent in para position to the phenolic group in the imine
(12) Sekar, G.; DattaGupta, A.; Singh, V. K. J. Org. Chem. 1998, 63,
2961.
(13) The aldehydes 6a,c are commercially available. For the
preparation of 6b, see: Hayashi, M.; Kaneda, H.; Oguni, N.
Tetrahedron: Asymmetry 1995, 6, 5743. 6d, see: Larrow, J. F.;
Jacobsen, E. N. J. Org. Chem. 1994, 59, 1939.
18
8d. The electronic effect of that substituent provided an e.e. of 92% in
the diethylzinc addition (entry 6). Thus, the enantioselectivity relies
mainly on the stereogenic center bearing a hydroxy rather than an amino
(14) Fleischer, R.; Wunderlich, H.; Braun, M. Eur. J. Org. Chem. 1998,
15e,19
20
1063.
group,
so that the novel amino alcohol 1 proved itself to be
superior to the regioisomeric compound 5. The role the
diarylaminomethyl group may play in asymmetric synthesis remains to
be determined by further investigations.
(15) For reviews on enantioselective variants of this reaction, see: a)
Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833. b) Noyori, R.
Asymmetric Catalysis in Organic Synthesis; Wiley: New York,
1994. c) Devant, R. M.; Radunz, H.-E. In Houben-Weyl, 4th ed.,
Vol. E21b; Helmchen, G., Ed.; Thieme: Stuttgart, 1995; p 1314. d)
Knochel, P. Synlett 1995, 393. Using catalysts with
diarylhydroxymethyl pattern: e) Soai, K.; Ookawa, A.; Kaba, T.;
Ogawa, K. J. Am. Chem. Soc. 1987, 109, 7111. f) Corey, E. J.;
Yuen, P.-W.; Hannon, F. J.; Wierda, D. A. J. Org. Chem. 1990, 55,
784. g) Seebach, D.; Plattner, D. A.; Beck, A. K.; Wang, Y. M.;
Hunziker, D. Helv. Chim. Acta 1992, 75, 2171. h) Bolm, C.;
Fernandez, K. M.; Seger, A.; Raabe, G. Synlett 1997, 1051.
Acknowledgment: This work was supported by the Fonds der
Chemischen Industrie. Grants to R. F. were provided by the
Graduiertenförderung and the Dr. Jost-Henkel-Stiftung.
References and Notes
(1) Braun, M. Angew. Chem. 1996, 108, 565; Angew. Chem., Int. Ed.
Engl. 1996, 35, 519.

December 1998
SYNLETT
1443
(16) According to a very recent paper, chiral imines have been used
independently as ligands in titanium mediated diethylzinc
additions: Mino, T.; Oishi, K.; Yamashita, M. Synlett 1998, 965.
2 H, NH ), 3.25 (br. s, 1 H, OH), 5.58 (s, 1 H, 1-H), 6.86–6.88 (m,
2
2 H, aromatic H), 7.06–7.32 (m, 11 H, aromatic H), 7.55–7.57 (m,
13
2 H, aromatic H); C NMR (75 MHz, CDCl ): δ = 65.6 (C-2),
3
77.4 (C-1), 126.4–128.2 (aromatic C), 139.7, 145.3, 145.8
(17) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969, 34,
+
+
(aromatic ipso-C); FAB-MS (NBA), m/z: 290 [M + 1], 289 [M ],
273 [Ph C(OH)CHPh], 272 [triphenyloxirane], 256 [Ph CCHPh],
2543.
2
2
(18) Jacobsen, E. N.; Zhang, W.; Güler, M. L. J. Am. Chem. Soc. 1991,
113, 6703. Braun, M.; Opdenbusch, K. Liebigs Ann./Recueil 1997,
141.
183, 182 [Ph C(NH )], 167 [Ph CH], 165 [fluorenyl cation], 154,
2
2
2
107 [PhCH(OH)], 106, 105 [PhC(NH ) and/or PhCO], 104
2
[PhC(NH)], 77, 51; C
H NO (289.4): calcd. C 83.01, H 6.62, N
20 19
(19) Cf.: Corey, E. J.; Hannon, F. J. Tetrahedron Lett. 1987, 28, 5233.
4.84; found C 83.16, H 6.73, N 4.69.
20
(20) Selected data of (S)-1: white solid; m.p. 152–153.5°C; [α]
=
D
1
-219 (c = 1, CHCl ); H NMR (500 MHz, CDCl ): δ = 1.90 (br. s,
3
3