Lewis Acid-Catalyzed And Gold-Catalyzed Propargylic Alcohols Rearrangement

Propargylic alcohols are valuable starting materials in organic chemistry,which can be easily functionalized further and used in bioorganic chemistry,pharmaceutical production and total synthesis of natural products.This dissertation describes the development and application of the rearrangement of propargylic alcohols catalyzed by Lewis acids and πacids.The Meyer-Schuster rearrangement is a straightforward and attractive strategy to synthesize α,β-unsaturated carbonyl compounds from secondary or tertiary propargylic alcohols.We firstly developed a Meyer-Schuster rearrangement catalyzed by Sm(OTf)3,and further study found the use of NFSI as an effective additive to enhance the activity of Sm(OTf)3 in the promotion of the Meyer-Schuster rearrangement.This new catalytic system affords several advantages such as high reaction yields,mild reaction conditions and short reaction times.Details of the mechanism were studied by performing a crossover experiment using heavy atom labeled substrates,and indicated that the reaction proceeded through a propargylic cation intermediate followed by an intermolecular nucleophilic addition of the hydroxyl group and tautomerization.We further expanded the utility of SmⅢ-NFSI catalytic system in other Lewis acid catalyzed reactions,including etherification,esterification,Baeyer-Villiger oxidation,Mukaiyama aldol reaction and Beckmann rearrangement.In each case,striking improvements in either the yields,reaction times,or temperatures were obtained.Based on these study,a NFSI/Lewis acid-catalyzed Beckmann rearrangement was developed and applied to transform erythromycin oxime into erythromycin 6,9-iminoether.At this time,the action model between NFSI and Lewis acids was probed by control experiments and theoretical calculations.The NFSI/Lewis acid system was also applied in Pinacol rearrangement.Its selectivity was firstly investigated by density functional theory(DFT)calculations.Then the tolerance of functional groups was examined by synthesizing a series of substrates designed based on the insight provided by the DFT calculations.The application of the methodology was demonstrated by the efficient one-pot synthesis of(±)-Latifine and(±)-Cherylline.The NFSI/Lewis acid system was also used in the AgOTf/NFSI catalyzed tryptamine-ynamide cyclization.This dissertation also described the gold(Ⅰ)-catalyzed oxidative rearrangement of propargylic alcohols to synthesize 1,3-diketones.We investigated the migration ability of sp3 carbon and sp2 carbon in oxidative ring expansion of cyclic-propargylic alcohols.The reaction of this type of substrate proceeded smoothly to deliver the only sp3 carbon migrated ring-expansion products in moderate to excellent yields.Based on this methodology,we developed a novel strategy to the total synthesis of Guanacastepenes,and completed the synthesis of a key intermediate.