Successive Transformations Of Multiple C-C/C-O/C-H Single Bond In Benzocyclobutenols Under Pd Catalysis

In the field of organic chemistry,the cleavage of C-Y(Y = C,H,O etc)single bonds has always been a challenging project due to the thermodynamic stability.The cleavages of multiple inert bonds in a single operation are even more formidable due to the incompatibility of conditions required for the conversion of each bond.Once realized,it would achieve the synthesis of complex molecules with high atom and step economy,which is a significant goal of environmentally benign synthesis.Benzocyclobutenol is an important kind of small-membered rings.The strained four-membered ring in the structure can be conveniently cleaved under hearting,base or transition-metal catalysis and are further converted to diverse organic compounds.Consequently,benzocyclobutenols are recognized as useful building blocks.To further extend their utilization in organic synthesis,we designed and synthesized3-allyloxybenzocyclobutenols and studied their reactions under Pd catalysis.It was found that different reaction pathways were involved depending on the substitutions on the substrates.For the reaction of α-alkyl substituted benzocyclobutenols with 1,1-disubstituted alkene moiety,a tandem proximal C-C bond cleavage/allylic alkylation reaction was realized.This reaction has the following characteristics:(1)three different C-C,C-O and C-H single bonds are successively cleaved with 100% atom economy;(2)the uncommon allylic alkylation of C-H bond using allylic ethers as electrophiles is achieved;(3)the α functionalization of ketones resulting from the C-C bond cleavage of benzocyclobutenols is realized for the first time;(4)an efficient synthetic approach to allylic-substituted meta-β-keto phenols is developed.For the reaction of α-alkyl substituted,3-butenoxybenzocyclobutenols,a tandem proximal C-C bond cleavage/deallylation reaction was achieved.It is worth to note that although a plenty of methods including Pd-catalyzed ones have been developed to remove the allylic group,these methodologies often require the use of reductants,strong acids or bases.Our work offered a complementary deallylation method under mildly basic conditions.For the reaction of α-aryl substituted,3-butenoxybenzocyclobutenols,a sequential distal C-C bond cleavage/deallylation reaction was achieved by using a one-pot,two-step procedure that involved the successive addition of base and Pd catalyst to the reaction system.Finally,sterically congested 2-acyl-3-methylphenols were efficiently synthesized.