Regiocontrolled Annulation Of Benzocyclobutenols With Alkynes

The direct activation of C–C single bond can realize the rearrangement of molecular skeletons and synthesize compounds that are difficult to access by traditional methods.However,this field has always been challenging due to the high energy of C–C bond and its surrounding by other chemical bonds.It was found that the strain release of small-membered rings could efficiently facilitate the C–C bond activation after extensive efforts.Among the various C–C bond functionalizations of small-membered-ring compounds,the transition-metal-catalyzed annulations with alkynes has attracted significant attention of chemists due to the high atom and step economies.Furthermore,these transformations may lead to the formation of compounds bearing alkene moiety,which is useful for further structural elaboration.Unfortunately,the reactions of asymmetrical alkynes usually suffered from poor regioselectivity.On the other hand,benzocyclobutenol is an important kind of small-membered rings,which can undergo selective C–C bond activation and functionalization under transition-metal catalysis to afford a variety of aryl compounds.However,the transformations of benzocyclobutenols mainly focus on intermolecular reactions.The intramolecular reactions,which would offer the opportunity to synthesize more complex compounds and have the inherent advantage to overcome the regioselectivity issue encountered in the intermolecular ones,are much less studied.This dissertation realized the intramolecular annulation of benzocyclobutanenols with alkynes for the first time.Moreover,the tethering oxygen group was successfully removed after the transformation,which resulted in the formal intermolecular annulation of benzocyclobutenols with alkynes with complete regiocontrol.Specifically,this dissertation mainly includes the following two parts:Firstly,considering that the naphtho-fused oxacycles are widely found in natural products and the ether group may be readily removed,the alkynyl substituted benzocyclobutenols tethered by an ether group were designed and synthesized.It was found that such moleculs could undergo intramolecular annulation/dehydration to afford 2H-furan-,pyran-and oxepine-fused naphthalene derivatives by using 1 mol%[Rh OH（cod）]₂as the catalyst,ⁿPr OH as the solvent,and 0.5equivalent of Zn Cl₂ as the Lewis acid.The methodology has the advantages of mild reaction conditions,wide substrate scope and high functional group tolerance.It is worth to note that naphthalenes with different substituents of similar characters at the 3,4-positions could be selectively synthesized simply by tuning the groups on the alkyne and alcohol moieties.Unfortunately,the reaction of benzocyclobutenols with alkynes tethered by an ester group failed to participate in the reaction under the standard conditions.Secondly,the removal of the bridging groups was attempted.It was found that 2H-naphtho[1,8-bc]furan may undergo reductive C–O bond cleavage by using Fe（acac）₃ as the catalyst,Li Al H₄ as the reductant and Na O^tBu as the base.Interestingly,the amounts of Li Al H₄and Na O^tBu had profound effects on the chemoselectivity of the reaction.When 3.0 equivalents of Li Al H₄ and Na O^tBu were used,the C（sp~3）–O bond may be selectively cleaved to afford 1-naphthols as the major product.When 1.5 equivalents of Li Al H₄ and Na O^tBu were used,the cascade C（sp~3）–O/C（sp~2）–O bond cleavage reaction selectively occurred to deliver multiple-substituted naphthalenes as the major products.Both of these transformations showed good functional group tolerance and could deliver the desired products in moderate to good yields.As a consequence,the regioselective intermolecular annulation of benzocyclobutenols with asymmetrical alkynes was realized through a“two-step”strategy.Unfortunately,2H-naphtho[1,8-bc]pyran and oxepine derivatives could not undergo the ring-opening reaction under the current conditions.