Studies On Transformations Of 2,3-allenoates And 2,3-Allenoic Acids

Allenes are a class of compounds with a 1,2-propadiene unit.The π orbitals of the two cumulated double bonds are perpendicular to each other resulting in a linear structure.The unique reactivities provide efficient protocols for the efficient syntheses of a large number of molecules.In addition,allene units are found in many natural products.The chemistry of allenes has been widely applied in pharmaceutical synthesis,materials chemistry,etc.Our group has been focusing on the syntheses and applications of allenes.I have focused my attention on the transformation of2,3-allenoates and 2,3-allenoic acids during my Ph.D.studies.Part Ⅰ:Catalyzed by the cheap metal oxide Cu₂O,the deuteration of 2,3-allenoates C（sp²）-H bond has been achieved affording 4-d-2,3-allenoates with the deuterium incorporation up to 92～97%D.The reaction enjoys an excellent functional group compatibility to give various 4-d-2,3-allenoates.The synthetic potentials of the 4-d-2,3-allenoates have also been demonstrated.The mechanism has been studied by KIE study,Hammett relationship studies,tandem mass spectrometry,and DFT calculation.Part Ⅱ:1.The cross-coupling of 2,3-allenoic acids with 2,3-allenols has been achieved under the catalysis of[Cp*RhCl₂]₂ with pure oxygen as oxidant affording a series of（E）-3-（5-oxo-2,5- dihydrofuran-3-yl）but-2-enals or enones.The reaction was compatible with 2,3-allenoic acids substituted with different functional groups such as halogens,phenethyl,and terminal olefins in the presence of 4-alkyl or aryl substituted 2,3-allenols.The reaction can be easily conducted on gram scale.2.[Cp*RhCl₂]₂catalyzed three-component cross-coupling reaction between 2,3-allenoic acids,2,3-allenols,and AcO^-has been achieved with Cu（OAc）₂·H₂O as oxidant.The reaction yields a series of formal 1,4-addition products of（E）-3-（5-oxo-2,5-dihydrofuran-3-yl）but-2-enals or enones with AcO^-and compatible with 2,3-allenoic acids bearing different functional groups as well as alkyl or aryl substituted 2,3-allenols.The reaction may be easily conducted on gram scale and the synthetic potential has been demonstrated.Detailed studies show a 1,4-H delivery mechanism driven by AcO^-.Part Ⅲ:Rh/Cu co-catalyzed cross-coupling of 2,3-allenoic acids with terminal alkynes affording 4-alkynylfuran-2（5H）-ones has been developed.In addition to the terminal alkynes and allenoic acids with common functional groups,the alkynes derived from complex natural product molecules are also compatible.Total synthesis of natural product appenolide A has been realized efficiently by applying this protocol.A mechanism has been proposed by detailed experimental studies:It’s noticed that air acts as oxidant realizing the regeneration of Rh（Ⅲ）from Rh（Ⅰ）.