The azide opening reaction of trans-2,3-epoxy alcohols with NaN 3 and PhB(OH) 2 in DMF occurred regio-and stereoselectively at the C-2 position giving rise to phenylboronates of trans-2-azido-1,3-diols in high yields, o 1999 Elsevier Science Ltd. All rights reserved.
Stereoselective epoxide-opening reactions have been recognized as one of the most important transformations in organic synthesis. 1 Among them, the azide opening reaction of 2,3-epoxy alcohols has gained importance in context with the synthesis of biologically active molecules. 2 Although various methods / reagents such as Me3SiN3-Et2A1F,3 NaN3-NH4CI,4
NaN 3 supported on calcium zeolite, 5 [Ti(O-i-Pr)2(N3)2],6 Bu3SnN3,7 Ti(O-i-Pr)4-Me3SiN3,8 Et2AIN3,9 etc. have been developed for the purpose, the regioselectivity in these azide opening reactions is restricted only at the C-3 position. On the other hand, examples pertaining to the C-2 selective azide opening of 2,3-epoxy alcohols are few, though isolated cases arising out of steric requirements 4 or the use of 2-trimethylsilyl-2,3-epoxy alcohols 10 have been reported. We have now developed a methodology to achieve the C-2 selective azide opening of trans-2,3epoxy alcohols by the combination of NaN 3 and phenylboronic acid (PhB(OH)2).
Although the C-2 selective azide opening reaction of 2,3-epoxy alcohols devoid of any steric and/or electronic bias has never been reported, we anticipated that the ring opening of such epoxy alcohols with NaN 3 and PhB(OH) 2 may occur regioselectively at the C-2 position by directing effect of PhB(OH)2, as shown in Scheme 1. Indeed, this was realized in practice very efficiently by using 3 equiv, of NaN 3 and 2 equiv, of PhB(OH) 2 in hot DMF to provide phenylboronates of the corresponding 2-azido-l,3-diols in high yields.