2054
J. C. Barrow et al. / Tetrahedron Letters 42 (2001) 2051–2054
acidic conditions. For example, treatment of 7a with
HCl in MeOH followed by removal of the volatile
by-products provided phenylglycinol in high yield and
purity (Scheme 4). Alternatively, if the synthetic
sequence requires a protected alcohol, similar treatment
of 7b provides 11b. Comparison of optical rotation for
11a and 11b to literature values13 established the stereo-
chemical assignment for the addition step.
1999, 64, 12–13; (e) Cogan, D. A; Ellman, J. A. J. Am.
Chem. Soc. 1999, 121, 268–269.
8. Davis, F. A.; McCoull, W. J. Org. Chem. 1999, 64,
3396–3397.
9. Both enantiomers of 1 are commercially available from
Aldrich Chemical Company or can be prepared as
described in Ref. 7b.
10. Older bottles of Grignard reagent also caused more of
this type of side reaction, presumably due to increased
amounts of Mg(OH)2.
11. 2-Pyridylglycinol: Cossu, S.; Conti, S.; Giacomelli, G.;
Falorni, M. Synthesis 1994, 12, 1429–1432.
12. Vinylglycinol: Campbell, A. D.; Raynham, T. M.; Taylor,
J. K. Synthesis 1998, 12, 1707–1709.
13. (a) 11a: Aldrich Catalog 1996–1997, p. 1162; (b) 11b:
Tetrahedron: Asymmetry 1996, 7, 3397.
In summary, addition of Grignard or lithium reagents
to 5 and 6 stereoselectively generates protected 1,2-
amino alcohols in high yield and diastereomeric purity
after silica gel chromatography. Removal of the acid
labile protecting groups affords free or O-benzyl pro-
tected 1,2-amino alcohols.14 Since factors that tradition-
ally favor chelate-controlled selectivity (non-coor-
dinating solvents, smaller oxygen protecting groups)
improve the observed product ratios, a bicyclic transi-
tion state model which invokes rapid E/Z isomerization
of the imine is proposed to rationalize the observed
selectivity.15 This methodology serves as a convenient
means of arriving at 1,2-amino alcohols for which the
optically active a-amino acids are not commercially
available or otherwise readily accessible.
14. Representative procedure: To a solution of 3.02 g (24.9
mmol) (R)-tert-butylsulfinamide (1) and 5.21 mL (27.4
mmol) of tert-butylsilyloxyacetaldehyde in 30 mL of
CH2Cl2 was added 8.74 g (54.7 mmol) CuSO4. The
reaction mixture was stirred at room temperature for 17
h and then filtered through Celite (400 mL CH2Cl2 rinse).
The filtrate was concentrated in vacuo. Purification on
the ISCO CombiFlash (120 g silica gel, 90 mL/min flow
rate, linear gradient 0–30% EtOAc:hexane over 30 min)
afforded 6.80 g (98%) of 5 as a white solid. 1H NMR
(CDCl3, 300 MHz) l 8.07 (t, 1H, J=3.05 Hz); 4.55 (d,
2H, J=3.05 Hz); 1.21 (s, 9H); 0.92 (s, 9H); 0.10 (s, 6H).
To a −78°C solution of 0.300 g (1.08 mmol) of 5 in 5.4
mL of CH2Cl2 was slowly added 0.720 mL (2.16 mmol)
of a 3 M solution of phenylmagnesium bromide in diethyl
ether. After 5 h at −78°C, the reaction mixture was
warmed to room temperature. After 17 h at room tem-
perature, the reaction was quenched with 15 mL of a
saturated NH4Cl solution and extracted with EtOAc (15
mL×3). The combined EtOAc fractions were washed with
15 mL of brine, dried over Na2SO4, filtered and concen-
trated in vacuo. Purification by flash chromatography
(40×105 mm silica gel, linear gradient 30–50%
EtOAc:hexane) yielded 0.260 g (66%) of 7a. 1H NMR
(CDCl3, 400 MHz) l 7.38–7.28 (m, 5H); 4.544–4.511 (m,
1H); 3.784 (dd, 1H, J=4.12 Hz, 10.07 Hz); 3.619 (t, 1H,
J=9.62 Hz); 1.234 (s, 9H); 0.908 (s, 9H); 0.062 (d, 6H,
J=8.06 Hz); MS (Electrospray): m/z 356.1 (M+H).
To a 0°C solution of 0.258 g (0.725 mmol) of 7a in 4 mL
of MeOH was added 0.720 mL (2.90 mmol) of a 4 M
solution of HCl in 1,4-dioxane. After 5 min at 0°C, the
reaction mixture was concentrated in vacuo to give 0.166
Acknowledgements
We thank Professor D. A. Evans for helpful
discussions.
References
1. Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996,
96, 835–837.
2. Evans, D. A.; Kim, A. S. In Encyclopedia of Reagents for
Organic Synthesis; Paquette, L. A., Ed.; John Wiley and
Sons: New York, 1995; Vol. 1, p. 345.
3. Deloux, S. Chem. Rev. 1993, 93, 763.
4. (a) Smith, G. A.; Gawley, R. E. Org. Synth. 1985, 63,
136–139; (b) Meyers, A. I.; McKennon, M. J. J. Org.
Chem. 1993, 58, 3568–3571.
5. O’Brien, P. Angew. Chem., Int. Ed. Engl. 1999, 38, 326.
6. (a) Davis, F. A.; Zhou, P.; Chen, B. C. Chem. Soc. Rev.
1998, 27, 13–18; (b) Davis, F. A.; Reddy, R. E.;
Szewczyk, J. M.; Reddy, G. V.; Portonovo, P. S.; Zhang,
H.; Fanelli, D.; Reddy, R. T.; Zhou, P.; Carroll, P. J. J.
Org. Chem. 1997, 62, 2555–2563.
7. (a) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.;
Ellman, J. A. J. Org. Chem. 1999, 64, 1278–1284; (b)
Cogan, D. A.; Liu, G.; Kim, K.; Backes, B. J.; Ellman, J.
A. J. Am. Chem. Soc. 1998, 120, 8011–8019; (c) Cogan,
D. A.; Liu, G.; Ellman, J. A. Tetrahedron 1999, 55,
8883–8904; (d) Tang, T. P.; Ellman, J. A. J. Org. Chem.
1
g (92%) of 11a in the form of a yellow solid. H NMR
(CD3OD, 400 MHz) l 7.48–7.40 (m, 5H); 4.335 (dd, 1H,
J=4.30 Hz, 8.43 Hz); 3.887 (dd, 1H, J=4.35 Hz, 11.58
Hz); 3.800 (dd, 1H, J=8.47 Hz, 11.58 Hz); MS (Electro-
spray): m/z 138.1 (M+H); [h]2D3=−26.7 (c=0.075, 1N
HCl); (lit.:13a [h]24=−31.7 (c=0.76, 1N HCl).
15. Since completion of this work, addition of ethylalu-
minum cyanoisopropoxide to a-hydroxy sulfinimines has
been reported: Davis, F. A.; Srirajan, V.; Fanelli, D. L.;
Portonova, P. J. Org. Chem. 2000, 65, 7663.
.