Diastereoselective Reduction of 1,3-Oxazolidin-2-ones and 1,3-Thiazolidin-2-ones

1,3-Oxazolidin-2-ones와 1,3-Thiazolidin-2-ones의 부분 입체 이성질체 선택적환원법

RESULT AND DISCUSSION

The di-tert-butyl-dicarbonate and dimethylaminopyridine (DMAP) were found to be useful for the synthesis of cyclic carbonates. Compound 1a has been prepared by condensing di-tert-butyl-dicarbonate with L-serine methyl ester hydrochloride in the presence of DMAP and triethylamine. Similarly 1b was prepared by condensing L-cysteine methyl ester hydrochloride with di-tert-butyl dicarbonate. 6

Encouraged by these findings this communication illustrates about the reduced products 1,3-oxazolidin-2-ols and 1,3-thiazolidin-2-ols, (Scheme 1) which are the intermediates in the synthesis of Loxazolidinyl and L-thiazolidinyl purine and pyrimidine nucleosides in our protocol.7

Unfortunately reduction of ester and lactone to the alcohol with variety of reagents such as diisobutylaluminium hydride, lithium borohydride and calcium borohydride was complicated.8 In the best case based on Brown et al.9 procedure, when both 1,3-oxazolidin-2-one and 1,3-thiazolidin-2-one were reduced using stereoselective reducing agent lithium triethylborohydride at -78 ℃ in tetrahydofuran, a mixture of primary and secondary alcohols were obtained and it was difficult to separate using column chromatography. Later we tried to reduce the same using lithium triethylborohydride at 0 ℃ in THF. Surprisingly reduction of lactone ring was achieved, but a trace amount of ester has been remained. Similarly we have carried out the reduction of both 1,3-oxazolidin-2-ones and 1,3-thiazolidin-2-ones (1a-d) using sodium borohydride in methanol at 0C, which afforded complete reduction of both lactone and ester functional groups with moderate yield compared to lithium triethylboro hydride.10

Scheme 1.

In addition, the reduction of N-tert-butoxy carbonyl 1,3-oxazolidine-2-one (1c) and N-tert-butoxycarbonyl-1,3-thiazolidine-2-one (1d) was carried out. Compound 1c was prepared by the condensation of 2-aminoethanol hydrochloride with di-tertbutyldicarbonate in the presence of DMAP and triethylamine and 1d was prepared by the condensation of 2-aminoethanethiol hydrochloride with di-tert-butyl-dicarbonate.11,12 We carried out the reduction of both 1c and 1d using both sodium borohydride and lithium triethylborohydride at 0C which afforded reduced products 2c and 2d respectively.13 The yield of lactol was good in lithium triethylborohydride compared to sodium borohydride and the spectroscopic data of the reduced products 2a-d are mentioned.14 All the synthesized compounds were purified by silica gel chromatography using chloroform : ethyl acetate (7:2) as the eluting solvents.

Table 1.

The diastereoselective reduction of these ester and lactum functional groups yields cis and trans diols using inexpensive sodium borohydrides and stereselective lithium triethylborohydrides.

 

EXPERIMENTAL

General procedure for the reduction of compounds 1a-d using Lithium triethylborohydride

To a cooled solution of (0C) of 1a-d (1.0 g, 4.92mmol) in THF (20 ml), 2 equivalent of 1M solution of lithium triethylborohydride (1.04g, 9.85 mmol) in THF was added and stirred for 1 h. After completion of the reaction, excess reagent was destroyed by the addition of saturated solution of NH4Cl at 0C, exctracted with dichloromethane (45 ml), dried over anhydrous MgSO4 and evaporated to dryness and purified by flash chromatography hexane ethylacetate (7:2) to afford the compounds 2a-d.

General procedure for the reduction of compounds 1a-d using Sodiumborohydride

To a cooled solution of (0 ℃) of 1a-d (1.0 g, 4.92 mmol) in methanol (20 ml), 2 equivalent of 1M solution of Sodiumborohydride (1.04g, 3.05 mmol) in methanol was added and stirred for 1 h. After completion of the reaction, excess reagent was destroyed by the addition of 10% HCl at 0 ℃, exctracted with ethylacetate (45 ml), dried over anhydrous MgSO4 and evaporated to dryness and purified by flash chromatography hexane: ethylacetate (7:2) to afford the compounds 2a-d.

In summary, 1,3-oxazolidine-2-ones and 1,3-thiazolidine-2-ones (1a-d) were reduced using both sodium borohydride and lithium triethylborohydride. Sodium borohydride reduces both lactone and ester functional groups successfully with moderate yield. Where as lithium triethylborohydride selectively reduces lactone with good yield but reduction of ester will be difficult. Efforts were pursued in our laboratory towards the reduction of other diastereoselective 1,3-oxazolidin-2-ones and 1,3-thiazolidin-2-ones following this methodology and will be reported in due time.