Acetylenic substitution reactions of cyclic sulfamidates

Acetylenic Substitution Reactions of Cyclic SulfamidatesUse of cyclic sulfamidates as versatile and reactive nitrogen containing electrophileshas recently began to be employed in a range of areas in synthesis. Of great value is the ringopening reactions with carbon-based nucleophiles forming a new C?C bond that could providea facile entry for the synthesis of functionalized amines. In this respect, the reactivity ofsulfamidates toward synthetically versatile carbon-based nucleophiles have been less widelyinvestigated in organic synthesis. A few substitution reactions of sulfamidates with somestabilized-carbon nucleophiles (mostly enolates) are known. Recently model studies conductedwith lithiumtriethylorthopropiolate indicate that cyclic sulfamidates could display a high level ofreactivity towards acetylenic nucleophiles.In this study, reactions of a representative set of structurally different cyclic sulfamidateswith acetylides prepared from various terminal alkynes were investigated in order to define thescope of the acetylenic substittution reactions of cyclic sulfamidates. Acidic hydrolysis ofsubstitution adducts affords ß-alkynlated amines. Primer carbon-centred 1,2-cyclic sulfamidatesshowed a high degree of reactivity towards conjugated, lineer, cyclic, heteroatomic, aromatic,heteroaromatic and functionalized acetylides. This reactivity profile enabled synthesis of ß-alkynlated amine compounds in high yields (%71-98). Solubility proplem was encountered forsome cases, due to aggregation of acetylides in THF. Addition of HMPA as a polar solvent in%10 portion not only overcome the solubility proplem but also increased reactivity ofsulfamidates significantly. Reaction of proline derived bicyclic 1,2- sulfamidate produced anadduct, which was unable to hydroylsis using various acidic conditions including standart 5MHCl conditions. Seconder carbon-centred efedrin derived 1,2-cyclic sulfamidate, without HPMA,failed to display any kind of reactivity level presumably due to steric factors. When HMPA usedas co-solvent, a complex reaction mixture resulted in. 1,2-Cyclic sulfamidate known for itsliability for elimination reaction gave not only substitution but also elimination products in %96overall yield (1:2 elimination compound as the major product). The same reaction with HMPAafforded the elimination compound as the sole product.Model substitution studies of phenylacetlylide and triethylorthopropiolate with the only1,3-cyclic sulfamidate studied demonstrated that beeing less reactive than 1,2-analogue, the1,3-sulfamidate still possesses synthetically useful level of reactivity when HMPA used as theco-solvent. Thus reactions of the 1,3-cyclic sulfamidate with phenylacetlylide andtriethylorthopropiolate gave corresponding substitution products in %75 and 80 yieldrespectively. However structure of the product obtained from the reaction oftriethylorthopropiolate was not the expected compound as judged by NMR spectroscopy. Thestructure of this compound was thought to be an alkylidene prolidine type heterocycliccompound. Formation of this heterocyclic product was rationalized from the pathway thatexpected substitution product under acidic conditions during the hydrolysis process of theintermediate N-sulfamate ester could undergo a facile conjuge addition onto the activated triplebond in intramolecular fashion to form an alkylidene prolidine heterocycle system. Furtherstudies are however required to establish the structure of this compound unambiguoulsy.IR, 1H NMR and 13C NMR techniques were used for structural characterization of thecompounds synthesized in this work.