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Organic Synteses vol 70 - Meyers A.I.

Meyers A.I. , Boecman R.K. Organic Synteses vol 70 - John Wiley & Sons, 1992. - 163 p.
ISBN 0-471-57743
Download (direct link): organicsynthesesvol701992.pdf
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7. Optical measurements on this material were not very useful since they were In general low and quite variable. Furthermore, no literature values could be found for comparison. IR (neat) crrr1: 3400, 1720 (br); 1H NMR (200 MHz, C6D6,17°C) 8: 1.41 (s, 9 H), 2.50 (br, s, H, exchanged with D20), 3.26 (s, 3 H), 3.66 (dd, H, J = 11 and 4), 3.76 (dd, H, J = 11 and 4), 4.40 (m, H), 5.60 (m, H, exchanged with D2O).
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8. Alternatively, the methyl ester could be prepared as follows: N-Boc-serine (63 g, 0.31 mol) was dissolved in ethyl ether (600 mL) in a 2-L Erlenmeyer flask equipped with a magnetic stirring bar, cooled in an ice-water bath and treated with ten 50-mL aliquots of cold ethereal (approximately 0.6 M) diazomethane prepared from N-nitroso-N-methylurea according to Arndt's procedure.3 After 30 min at 0°C, TLC analysis showed the reaction to be complete (Note 6). Excess diazomethane was destroyed with acetic acid (the yellow color disappears) and the resulting solution was extracted with half-saturated sodium bicarbonate solution (300 mL), then washed with brine (200 mL), dried with magnesium sulfate, filtered and concentrated to give 60.1 g (91% over 2 steps) of N-Boc-serine methyl ester as a colorless, sticky foam which was used without further purification. CautionI N-Nitroso-N-methylurea is suspected of being a carcinogen and diazomethane is highly toxic. The utmost care must be used when handling these substances; diazomethane solutions should be restricted to a well-ventilated fume hood at all times.
9. Moriwake et al. have reported that boron trifluoride etherate can also be used as the acid catalyst for this reaction.6
10. TLC analysis on Merck silica gel 60F-254 plates eluting with (1:1) ethyl acetate-hexanes showed the clean formation of product, Rf 0.78 (visualized with 0.5% phosphomolybdic acid in 95% ethanol), at the expense of starting material at Rf 0.23.
11. If starting material remained at this time, more 2,2-dimethoxypropane (14 mL, 12 g, 0.11 mol) and benzene (310 mL) were added and the procedure was repeated, collecting 250 mL of distillate, at which time the TLC analysis generally showed the reaction to be complete.
12. The optical rotation of the L-oxazolidine methyl ester was -46.7° (CHCI3, c 1.30). An essentially identical procedure emanating from N-Boc-D-serine methyl ester gave the corresponding D-oxazolidine methyl ester in 80% yield with a rotation of +53°. In either case further purification could be achieved with flash chromatography
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to give product with a maximum rotation of 57° although we have found distilled material to be entirely satisfactory for our purposes: IR (neat) cm'1: 1760, 1704; 1H NMR (200 MHz, C6D6, 75°C) 8: 1.41 (s, 9 H), 1.53 (br s, 3 H), 1.81 (br s, 3 H), 3.35 (s,
3 H), 3.75 (dd, H, J = 8.5 and 8.1), 3.81 (dd, H, J = 8.5 and 3.5), 4.26 (m, H). (The oxazolidine derivatives exist as slowly interconverting rotamers on the NMR time scale and samples require heating to obtain averaged spectra.)
13. All the glassware (except the low-temperature thermometer) was oven-dried (>100°C) and quickly assembled before use.
14. The checkers used argon.
15. Toluene was distilled from sodium-benzophenone ketyl.
16. The diisobutylaluminum hydride solution (1.5 M in toluene, Aldrich Chemical Company, Inc.) was transferred to a dry, 250-mL, graduated cylinder equipped with a rubber septum and drying tube via cannula (using positive nitrogen pressure). The graduated cylinder was then placed in a Dewar flask and cooled to -78°C with an acetone-dry ice bath.
17. TLC analysis on Merck silica gel 60F-254 plates eluting with (4:1) hexanes-ethyl acetate showed the formation of product, Rf 0.33 (visualized with 0.5% phosphomolybdic acid in 95% ethanoi), with only a trace of starting material remaining at Rf 0.41. Some over-reduced product arising within the TLC capillary may be evident at this stage.
18. The optical rotation of the L-oxazolidine aldehyde was -91.7° (CHCI3, c 1.34). An identical procedure emanating from the D-oxazolidine methyl ester gave D-oxazolidine aldehyde in 85% yield having a rotation of +95°. These distilled products contained up to 5% of the starting material as judged by their NMR spectra, but were suitable for use without further purification. Homogeneous samples could be obtained in either case by flash chromatography on silica gel eluting with (4:1) hexanes-ethyl acetate and showed a maximum optical rotation of 105°. This material can be stored
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indefinitely provided it is kept cold (< 5°C) and moisture-free. IR (neat) crrr1: 1735, 1705; 1H NMR (200 MHz, C6D6, 60°C) 6: 1.34 (s, 9 H), 1.40 (brs, З H), 1.59 (brs, З H), 3.52 (dd, H, J = 8.7 and 8.3), 3.65 (dd, H, J = 8.7 and 2.9), 3.90 (m, H), 9.34 (br s, H).
Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent Practices for Disposal of Chemicals from Laboratories"; National Academy Press; Washington, DC, 1983.
3. Discussion
Since its preparation and use was first reported by us,4 the title compound has been gaining favor as a chiral, nonracemic synthon for the asymmetric synthesis of a variety of amino alcohol- and amino acid-containing targets. Among the virtues of this oxazolidine aldehyde over previously reported N-acylated serinal derivatives are its ease of preparation on a large scale and its configurational stability. The procedure described here provides material that has been determined to be 95% enantiomerically pure by Mosher ester analysis.7 Homologation (C-C bond formation) of this serinal derivative can be achieved without competing racemization using both olefination6’15’22-26 and nucleophilic addition4'5'8'14'16-21 protocols. The latter process can be made to occur with good to excellent diastereoselectivity (i.e., 1,2-asymmetric induction) by simply choosing reagents/conditions so as either to preclude or favor chelation-control. Protocols for diasteroselective additions to the oxazolidine appended olefins are also known. Once the rest of the target molecule's structure is in place, the oxazolidine can be unravelled to give either an aminoethanol group or, after oxidation of the primary alcohol, an a-amino acid moiety. The products so produced
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