Asymmetric Desymmetrisation Of 1,4-diolefins Via Stetter Reaction

N-Heterocyclic Carbene (NHC) catalyzed asymmetric desymmetrisation of 1,4-diolefins via the intramolecular Stetter reaction was demonstrated. This dissertation contains the following three main aspects:1?Conditions optimization for NHC catalyzed asymmetric desymmetrisation of 1,4-diolefins via the intramolecular Stetter reaction1,4-diolefin 1a with an ester substituent was selected as the model substrate for the conditions optimization. A variety of catalysts, bases, solvents, additives and temperatures were evaluated and the optimal reaction conditions were finally established with C5 as the catalyst, KOtBu as the base, toluene as the solvent and running at-25 ? for 6 hours without additive. Product 2a was made under this conditions with 99% yield, 7.2:1 dr and 99% ee.2?The substrate scope of NHC catalyzed asymmetric desymmetrisation of 1,4-diolefins via the intramolecular Stetter reaction.A wide range of 1,4-diolefins with ester or ketone substituents work well under the optimal conditions. In some cases, a higher temperature such as 0 ? or room temperature is necessary to achieve smooth conversions, with no erosion in the enantioselectivities. The ee of 1,4-diolefins with ester or ketone are higher than 90%and 80%, respectively. Disappointedly, efforts to generate three chiral centers failed. Moreover, substrates with aliphatic formyl groups released the corresponding products in high yields and with low enantioselectivities.3?Derivatizations of products obtained from the NHC catalyzed asymmetric desymmetrisation of 1,4-diolefins via the intramolecular Stetter reaction.Further derivatizations of the annulation products were realized through chemoselective catalytic hydrogenation and stereoselective allylation, demonstrating the synthetic potential of this protocol.