A pinacol coupling approach to N-heterocycles : synthesis of iminosugars

A series of 5-8 membered N-heterocyclic diols have been prepared from dicarbonyls (shown below), via intramolecular pinacol reactions. The cis- or trans-stereoselectivity of these reactions is controlled by judicious choice of the low-valent metal reagent employed. The diastereoselectivity of the pinacol products is pleasingly comparable with literature examples, albeit with lower levels of stereocontrol in some cases than the corresponding carbocyclic systems. Deprotection to yield the corresponding novel amino diols has also been undertaken so that biological testing could be performed. (Fig. 10988).;In addition a novel reaction has been developed whereby an ozonide precursor is treated with SmI2 to carry out both ozonide reduction and pinacol coupling in the same pot to yield the corresponding -heterocyclic diol.;Trihydroxypiperidines, such as 1,5-dideoxy-1,5-imino-arabinitol have been synthesised in order to investigate and explain the 'directing' effects alpha-alkoxy substituents have on the stereoselectivity of the pinacol reaction. The levels of stereoselectivity of the reaction were good, but lower that the comparable carbocyclic cases. To the best of our knowledge we have also carried out the first titanium-mediated (Cp 2TiPh) pinacol coupling of an alpha-alkoxy substituted dicarbonyl which proceeds with a good level of diastereoselectivity.;Ring-closing metathesis with Grubb's catalyst and dihydroxylation with osmium tetroxide reactions have been applied as an alternative method for the synthesis of a series 6- and 7-membered of N-heterocycles. These products were compared to the products synthesised via pinacol coupling reactions to confirm their stereochemistry.