Application of the Oxo Reaction to Glycals

When 3,4-di-O-acetyl-D-xylal (5), prepared by a modification of the procedure of Helferich and coworkers, was allowed to react with a mixture of carbon monoxide and hydrogen at a pressure of about 4000 Ib./in. and at a temperature of about 130° for about 90 minutes, in the presence of preformed dicobalt octacarbonyl in benzene as the catalyst, a mixture of two inseparable, partially acetylated hexitols was obtained in over 90% yield. Deacetylation of the latter with sodium methoxide in methanol yielded, in almost equimolar proportions, the chromatographically separable hexitols, l,5-anhydro-4-deoxy-L- yio-hexitol (6) and l,5-anhydro-4-deoxy-D-arahino-hexitol (7). Whenever the mixture of products was contaminated by the precursor aldehydo compounds, a prior reduction of these with sodium borohydride greatly facilitated the isolation of (6) and (7) in pure form. 

In addition to conducting classical structural studies of (6) and (7) by correlating the newly formed asymmetric center at C-5 with that of a known compound, the authors deduced the stereochemistry involved in this oxo reaction by a p.m.r. study of partially deuterated analogs of (6) and (7). The p.m.r. study is discussed in Section III, 6 (see p. 74). 

The stereochemistry at C-5 of each of the hexitols (6) and (7) was determined in the following way. Periodate oxidation of these hexitols afiForded dialdehydes (8) and (9), which, on subsequent reduction with sodium borohydride, afforded the enantiomeric trihydroxy ethers (10) and (11). The configuration at C-3 of the ether (10) was then correlated with that of C-4 of the known l,4-anhydro-5-deoxy-D-arabino-hexitol (12), as follows. Periodate oxidation of (12), followed by reduction of the resulting dialdehyde with sodium borohydride, yielded a trihydroxy ether that was identical with (10). If it is assumed that no inversion of configuration at C-3 or C-4 of 3,4-di-O-acetyl-D-xylal occurs during the oxo reaction, then compounds (6) and (7) are l,3-anhydro-4-deoxy-L-JC /lo-hexitol and l,5-anhydro-4-deoxy-D-arobino-hexitol, respectively. 

Application of the oxo reaction (as described in Section 111,2) to 3,4-di-O-acetyl-D-arabinal (20), followed by deacetylation and chromatographic separation of the products (obtained in at least 90% yield), afibrded l,5-anhydro-4-deoxy-L-riho-hexitol (21) and 1,5-anhydro-4-deoxy-D-li/xo-hexitol (22), in the ratio of 0.7 to 1.0. Structural investigations of (21) and (22) were performed as described previous ly, with the results shown. 

In connection with preliminary structural work on the hexitols, an unexpected result arose during attempted identification, by conversion into a (p-nitrophenyl)hydrazone, of the dialdehydes (8) or (9), formed by periodic acid oxidation of tbe anhydrodeoxyhexitols (6) and (7), or (21) and (22). The dialdehydes (8) were cleaved to form glyoxal and a 2-deoxytetrose [isolated as the (p-nitrophenyl)hydra-zone ]. 

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