Lewis Acid-catalyzed Unsaturated Alcohol Hydroxyl Activation

This dissertation mainly focuses on the Lewis acid-catalyzed activation of hydroxy group in alcohols and some related reactions.The dissertation can be divided into four parts.Firstly,we have found that Yb(OTf)₃ can catalyze the direct substitution of the hydroxy group in allylic alcohols with a variety of heteroatom-centered nucleophiles, such as alcohols,thiols,amines and amides,to give the corresponding allylation products in good to excellent yields under mild reaction conditions.The advantages of current catalyst system are high chemistry selectivity and easy to recycle the catalyst.Secondly,we have investigated the coupling reaction of allylic alcohols and benzyl alcohols with active methylene compounds catalyzed by lanthanide Lewis acid,which provides an efficient route to synthesis of 2-alkyl-1,3-dicarbonyl compounds and are wide availability of the starting materials.It is noteworthy that the present catalyst is also high efficient for the direct hydroxy substitution of allylic alcohols with the acidic diethyl malonate.Furthermore,we have found that the Yb(OTf)₃-catalyzed reaction of secondary propargylic alcohols with 1,3-dicarbonyl compounds also proceeds smoothly to give the corresponding propargylation products.However,the treatment of tertiary propargylic alcohols with 1,3-dicarbonyl compounds gives the allenylation products under the same conditions.In addition,catalytic quantities of Yb(OTf)₃ can also effectively promote the propargylation and allylation of 4-hydroxycoumarins at the 3-position.By applying this reaction as the key step,a multi-substituted bioactive furocoumarin can easily be synthesized in a one-pot procedure.Thirdly,we have studied the intramolecular cyclization reaction of tertiary propargylic alcohols.We have designed and synthesized a variety of benzylamino-substituted propargylic alcohols.Treatment of these propargylic alcohols with 5 mol%of FeCl₃·6H₂O led to the occurrence of the tandem activation of hydroxy group/isomerization/cyclization reactions,giving tetrahydroisoquinolines in moderate to good yields,which provides a mild,versatile and efficient method for the one-step synthesis of substituted tetrahydroisoquinolines and represents the first example of the intramolecular Friedel-Crafts reaction of propargylic alcohols. Moreover,it was found that some substituted tetrahydroisoquinolines can be further transformed into dihydroisoquinoline derivatives under suitable conditions and the structures of some products have been further confirmed by X-ray single diffraction analysis.Finally,in the investigation on the intramolecular Friedel-Crafts reaction of ester-substituted propargylic alcohols,we have observed an unexpected tandem cyclization reaction that allows one-step synthesis of spirocyclics and polycycles. Significantly,the tandem cyclization is controllable,for which the dihydro-and tetrahydronaphthalene intermediates can be selectively isolated by changing the reaction conditions or catalyst.Based on this result,a reasonable mechanism for these reactions has been presented.Further investigation results demonstrate that chemoand regioselectivities of the second-step cyclization reaction strongly depends on the nature of substituents at the resulting ring and the nucleophilicity of the aryl rings.In addition,we have researched the intramolecular cyclization reactions of MOM-and EOM-substituted propargylic alchohols,and synthesized a variety of bioactive skeleton unit hydrogenated naphthalene compounds.