Synthesis Of Chiral Complex Polycyclic Compounds By Rhodium

Many biologically active natural products and drug molecules contain complex ring systems,such as spiro rings,bridged rings and polycyclic systems.How to synthesize these complex chiral ring systems in the most efficient and selective pathway is very important in organic synthesis.Traditional methods for synthesizing chiral complex polycyclic compounds usually require multi-step reactions,which are relatively inefficient,and the establishment of multiple chiral centers in these reactions is also a big challenge.The transition metal-catalyzed cyclization reaction of 1,6-enynes,especially the asymmetric cyclization reaction,is an important synthetic method to construct polycyclic systems,but many problems of this reaction still remain.For example,the conditions of some catalytic reactions are relatively harsh,requiring equivalents of acids or bases;temperature is relatively high;the reaction type is relatively limited;the substrate scope is narrow,and so on.Therefore,it is very important to develop more efficient catalytic systems to synthesize diverse chiral complex polycyclic compounds.Therefore,we focused on the asymmetric rhodium catalytic system,to realize the cyclization reaction of 1,6-enynes.In this thesis,we developed the following three new reactions for the construction of chiral complex polycyclic rings by asymmetric rhodium-catalyzed cyclization of 1,6-enynes:In chapter ?,the tandem reaction of hydroalkynylation in "head-to-head" mode and desymmetrical Michael addition cyclization has been developed.This reaction can construct the hydrobenzofuran moiety containing two consecutive chiral centers in one step,and it has 100%atom economy.The reaction is carried out at room temperature,no additives such as acid or base are needed,and a series of enantioenriched enynes bearing an important chiral cis-hydrobenzofuran moiety were obtained in one step with excellent chemo-,regio-,diastereo-,and enantioselectivity.This is a new synthetic strategy to achieve selective hydroalkynylation of non-activated alkynes to obtain conjugated chiral enynes of single isomer.In chapter ?,asymmetric synthesis of a fused tricyclic hydroriaphthofuran scaffold by desymmetric[2+2+2]cycloaddition has been developed.In this reaction,diverse fused tricyclic hydronaphthofuran scaffolds with three consecutive stereogenic centers were constructed in one step with excellent chemoselecyivity and steoreoselectivity.Notable features of these reactions include 100%atom economy.First,a desymmetric oxidative cyclization of 1,6-enynes with Rh?/BINAP occurs,leading to a chiral rhodacyclopentene.Alkyne coordination followed by insertion to the triple bond generates the intermediate,and subsequent reductive elimination gives tricyclic product.Rhodium-catalyzed asymmetric cyclization of 1,6-enynes usually produces bicyclic products and this is the first rhodium-catalyzed asymmetric cyclization reaction of 1,6-enynes to construct chiral fused tricyclic compounds.Diverse functionalized penta-substituted tricyclic benzene derivatives could be produced efficiently by further transformations in one-step.This method offers an elegant approach to the de novo construction of chiral pentasubstituted benzene derivatives.In Chapter ?,asymmetric synthesis of pyrans by intramolecular[2+2+2]cyclization reaction of 1,6-enynes has been developed.Pyrans are an important class of compounds.It is the basic structure of most glycoside compounds(such as glucose,arabinose,etc.).Many important natural products such as pigments,sugars,antibiotics,alkaloids,etc.contain the ring systems of pyrans or pyran salt.We found that the complex of Rh(cod)2BF4 and spiro diphosphine ligand SDP is the efficient catalytic system for this reaction.Under optimal reaction conditions,a series of 1,6-enynes can be converted into corresponding pyran derivatives with up to 98%ee.A series of important chiral 1,5-dicarbonyl compounds could be produced efficiently by further transformations.In Chapter ?,an gold-catalyzed intramolecular cycloisomerization of alkynyl alcohol and intermolecular spiroketalization reaction with quinone monoimines has been developed.Under mild conditions,various 5,5-benzannulated spiroketals were obtained from available starting materials.This methods provides an atom-economical synthesis of complex polycyclic heterocycles.