Studies On The Reactions Of Allenes And Asymmetric Allenylations

Allenes are a class of unique compounds with an axial chirality spreading over three carbon atoms and widely exist in natural products and bioactive molecules.So far,more than 220 natural products comprising an allenic structure are known.Allenes has been studied showing novel patterns for construction of various molecules with excellent regio-and stereoselectivity via its unique reactivity.In the meantime,allenes have been applied as the key intermediates in the synthesis of complex molecules and natural products.Therefore,allenes have received much attention due to its unique physical,biological and chemical properties.Based on this,I have focused on the total synthesis of naturally occurring carbazole alkaloids via an efficient Au-catalyzed cyclization reaction of allenols,conjugate addition of allenes with organozinc reagents,and palladium-catalyzed asymmetric allenylation reaction during my Ph.D.study.The dissertation includes the following three parts:Part Ⅰ:Total synthesis of naturally occurring carbazole alkaloids.Studies on carbazole alkaloids have been an imperative research topic in recent years due to their potential biological activities.Here,naturally occurring carbazole alkaloids including 2-hydroxy-3-methylcarbazole,girinimbine,murrayacine,mukoenine-A,and heptaphylline have been synthesized on gram scales.The key compound in these syntheses is 9-benzyl-2-methoxy-3-methylcarbazole,which was prepared by an efficient Au-catalyzed cyclization reaction of readily available methoxypropadiene and indole-2-carbaldehyde.Girinimbine and murrayacine were synthesized by a concise PhB(OH)2-mediated intermolecular cyclization with 3-methylbut-2-enal.The palladium-catalyzed allylation/Claisen rearrangement opened up so far the best route to mukoenine-A and heptaphylline.Part II:Conjugate addition of 2,3-allenals with organozinc reagents.Stereodefined construction of tetrasubstituted olefins is a significant challenge in organic synthesis.Here we show a practical method for the preparation of stereodefined fully substituted olefins via conjugate addition of organozinc reagents to readily available 2,3-allenals.Through mechanistic studies,we proposed that conjugate addition of R2Zn with 2,3-allenals would form the zinc dienolate intermediate,then the dienol was formed by delivering the proton regiospecifically to the anionic oxygen atom.The stereodefined olefins was finally formed exclusively via the concerted intramolecular 1,5-hydride transfer.Using the readily available organozinc reagents and 2,3-allenals provides a very rapid access to a wide range of tetrasubstituted olefins with defined stereochemistry.Part III:Palladium-catalyzed asymmetric allenylation reaction.Despite many advances for obtaining chiral molecules with a single type of chirality have been reported recent years,simultaneous stereodefined construction of chiral molecules which have different types of chiralities is still a significant challenge as well as the key area of study for asymmetric chemistry.Allenylation reactions of racemic allenes has interestingly been applied for generating allenes with a central or axial chirality under the catalysis of chiral palladium catalysts,but so far development of such catalytic enantioselective reactions for obtaining allenes with both central and axial chiralities has not been established.Here,we realized a general and practical approach to chiral allenes bearing both central and axial chiralities with excellent enantioselectivity using a single chiral ligand in mild conditions via catalytic asymmetric allenylation of readily available racemic poly-substituted 2,3-allenyl acetate with a series of useful nucleophiles.