Studies on Au-catalyzed Cycloisomerization of Allenoic Acids and Its Application in Synthesis of Natural Lactones

Author:Zhou Jing

Supervisor:ma sheng ming fu chun ling

Database:Doctor

Degree Year:2018

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Pages:346

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Allenes are a class of compounds containing a cumulative diene structural unit,which could be loaded with different functional groups.In principle,any one of the three carbon atoms on the cumulative diene structural units may be attacked by different reagents,thereis an issue of controling the selectivity.So far,many efforts have been made on the electrophilic addition or cyclization reactions of functionalized allenes activated by Lewis acids.As one class of the common Lewis acids,the affinity of 7c bonds towards the Au catalysts through the strong polarization make the cumulative diene vulnerable to the attack of different nucleophilic heteroatoms such as oxygen,nitrogen and sulfur etc.During my Ph.D.study,I foucused my attention on the Au-catalyzed cycloisomerization of allenoic acids:Firstly,we explored the optimal reaction conditions for Au-catalyzed stereoselective cyclization of 4,5-allenoic acids,focusing mainly on the regio-and stereo-selectivity.The high optically active 4,5-allenoates could be easily prepared via the CuBr2_catalyzed EATA reaction(Enantioselective Allenylation of Terminal Alkynes)developed by Dr.HuangXin in our group.Through hydrolysis,4,5-allenoic acid was obtained.By using the monophosphine ligands by Dr.Lv Bo,AuCl(LB-Phos)has been prepared.Then γ-(E)-vinylic γ-butyrolactones was formed by the AuCl(LB-Phos)/AgOTs catalyzed intramolecular cyclization of 4,5-allenoic acids.With this rather sterically bulky AuCl(LB-Phos),gladly,a high E/Z selectivity was observed,indicating that the new catalyst was able to control both the C=C stereoselectivity(E/Z ≥ 97:3)and ensure the efficiency of chirality transfer.This approach offers an efficient strategy for constructing enantioselective y-butyrolactones.y-Alkyl-y-butyrolactones were easily obtained just by further hydrogenation of the C=C bond in y-vinylic y-butyrolactones.With the optimized reaction conditions in hand,we then paid our attentions to its application in the synthesis of natural lactones.As we know,y-butyrolactones exist extensively in nature and have drawn much attention due to their interesting biological potentials.We have synthezed some selected natural y-butyrolactones.such as(R)-4-tetradecalactone,(S)-4-tetradecalactone,(R)-γ-palmitolactone,and(R)-4-decalactone;optically active xestospongienes E-H,(R)-and(S)-traumatic lactones,rac-rhizobialide,and natural rhizobialide via the AuCl(LB-Phos)-catalyzed cycloisomerization of 4-allenoic acids successfully.We have also explored the total synthesis of rubrenolide and rubrynolide.It is worth noting that(R)-4-decalactone and xestospongienes F have been synthesized on gram scales;xestospongienes E-H were synthesized for the first time and the absolute configurations of the chiral centers in xestospongienes E and F have been revised according to our syntheses;optically active(R)-traumatic lactone,(S)-traumatic lactone and rac-rhizobialide were also prepared for the first time;high optically active rhizobialide has been synthezed as well.These successful syntheses show that our method has great potential in preparition of y-butyrolactone-like natural compounds.