LETTER
added dropwise, followed directly by aq hydrolysis. Once
Lithiated Dimethoxymethyl Diphenyl Phosphine Oxide
527
C-4).
the mixture is warmed up to r.t. it was concentrated in vacuo.
After the resulting aq suspension was extracted with
dichloromethane (5 ), the combined organic layers were
dried over MgSO4 and evaporated. The residue was purified
by column chromatography (silica gel; petroleum ether/ethyl
acetate 1:4) to yield the adduct 18 (353 mg, 0.63 mmol,
42%).
(anti-25); Mp 120 °C (CH2Cl2); [a]22.5D +73.6, (c 1.0,
CHCl3); 1H NMR (200 MHz, CDCl3): = 7.40–7.14 (m, 10
H, H-aromat.), 5.12 (d, J = 8.8 Hz, 1 H, NH), 5.05 (s, 2 H,
PhCH2O), 4.41 (m, 1 H, 3-H), 4.34 (m, 1 H, 2-H), 3.57 (s, 3
H, OMe), 3.22 (s, 1 H, OH), 2.8 (m, 2 H, 4-H); 13C NMR (50
MHz, CDCl3): = 173.0 (s, C-1), 155.9 (s, NCO2), 136.8,
136.3 (d, C-aromat.), 129.4, 128.5, 128.4, 128.1, 128.0,
126.7 (s, C-aromat.), 72.2 (d, C-2), 66.8 (t, PhCH2O), 54.6
(d, C-3), 52.7 (q, OMe), 35.6 (t, C-4).
Selected spectroscopic data for adduct 18: 1H NMR (200
MHz, CDCl3): = 8.12–7.75 (m, 4 H, H-aromat.), 7.55–7.08
(m, 14 H, H-aromat.), 7.05–6.94 (m, 2 H, H-aromat.), 6.08
(d, J = 6.8 Hz, 1 H, OH), 5.08 (d, J = 1.8 Hz, 1 H, NH), 4.96
and 4.82 (2 d, J = 12.5 Hz, 2 H, PhCH2O), 3.90 (m, 2 H, 1-
H, 2-H), 3.29 and 3.19 (2 s, 6 H, 2 OMe), 2.94 (m, 2 H,
PhCH2); 13C NMR (100 MHz, CDCl3): = 157.2 (s, NCO2),
138.3, 136.7, 133.0, 132.8 (s, C-aromat.), 2 132.1, 131.9,
The absolute and relative configuration of both
diastereomers 25 was independently confirmed after t-
BuOK-promoted elimination followed by asymmetric
dihydroxylation using ADmix- (affording anti-25) or
ADmix- (affording syn-25). The configuration was
determined as described in ref.14 (Scheme 4).
2
131.7, 2 131.6, 131.5, 131.4, 129.2, 128.6, 128.4,
128.3, 128.2, 2 128.1, 2 127.8, 126.0 (d, C-aromat.),
103.9 (s, C-3), 74.8 (d, C-2), 66.3 (t, PhCH2O), 60.4 (d, C-
1), 52.6 (q, OMe), 51.7 (q, OMe ), 38.2 (t, CH2Ph).
1. KOtBu, THF
0 °C, 10 min
2. ADmix-α, MeSO2NH2,
H2O, tBuOH 1:1,
Ph
OH
(10) Typical Experimental Procedure for the Generation of -
Hydroxy Esters by Proton-induced Fragmentation:
Dichloromethane (200 mL) and hydrochloric acid (2 N, 10
mL) were stirred for 10 min. The aq phase was seperated and
the acidity (1.5 mmol/L) of the organic phase was
Ph
OH
O
P
0 °C, 4h
OMe
Ph
Ph
OMe
ZHN
O
MeO
70%
ZHN
anti-25
18
determined by titration with 0.1 N NaOH. (2RS,3S)-3-
Benzyloxycarbonylamino-2-hydroxy-4-phenyl butyric acid
methyl ester(25): Acidic dichloromethane (1.5 mL) was
added to a solution of the phosphine oxide 18 (112 mg, 0.2
mmol) in dichloromethane (3 mL). The pure ester 25 was
obtained after gel filtration (67 mg, 0.195 mmol, 97.5%).
Selected spectroscopic data for the hydroxy ester: (syn-25);
Mp 92 °C (CH2Cl2); [a]23D +7.9 (c 1.0, CHCl3); 1H NMR
(400 MHz, CDCl3): = 7.38–7.20 (m, 10 H, H-aromat.),
5.09 (d, J = 8.0 Hz, 1 H, NH), 5.04 (s, 2 H, PhCH2O), 4.33
(dddd, J = 8.9, 8.0, 7.1 and 1.8 Hz, 1 H, 3-H), 4.08 (d, J = 1.8
Hz, 1 H, 2-H), 3.70 (s, 3 H, OMe), 2.94 (s, 1 H, OH), 2.97
and 2.89 (2 dd, J = 13.2 and 8.9 Hz, J = 13.2 and 7.1 Hz,
Scheme 4
(11) The preparation of aldehyde 11 was achieved according to:
Steurer, S.; Podlech, J. Eur. J. Org. Chem. 1999, 1551.
(12) Reviews on the Horner–Wittig reaction: (a) Clayden, J.;
Warren, S. Angew. Chem., Int. Ed. Engl. 1996, 35, 241;
Angew. Chem. 1996, 108, 261. (b) Maryanoff, B. E.; Reitz,
A. B. Chem. Rev. 1989, 89, 863.
(13) van Schaik, T. A. M.; Henzen, A. V.; van der Gen, A.
Tetrahedron Lett. 1983, 24, 1303.
(14) (a) Kirschning, A.; Dräger, G.; Jung, A. Angew. Chem., Int.
Ed. Engl. 1997, 36, 253; Angew. Chem. 1997, 109, 253.
(b) Monenschein, H.; Dräger, G.; Jung, A.; Kirschning, A.
Chem. Eur. J. 1999, 5, 2270.
2
1 H, 4-H, 4-H ); 13C NMR (100 MHz, CDCl3): = 174.1
(s, C-1), 155.7 (s, NCO2), 137.2, 136.3 (s, C-aromat.), 129.4,
128.6, 128.5, 128.1, 127.9, 126.7 (d, C-aromat.), 70.1 (d, C-
2), 66.8 (t, PhCH2O), 54.7 (d, C-3), 52.9 (q, OMe), 38.3 (t,
(15) Sourkouni-Argirusi, G.; Kirschning, A. Org. Lett. 2000, 2,
3781.
Synlett 2002, No. 3, 525–527 ISSN 0936-5214 © Thieme Stuttgart · New York