Friedel-crafts Alkylation Of Nitroalkenes With Indoles At The C7-position And The Total Synthesis Of Conidiogenone B

The Friedel-Crafts reaction of indoles and nitroalkenes has been an important method to generate indole derivatives.The reaction usually occurs at the C3-position of indoles,and there is no report on the Friedel-Crafts reaction at the C7-position of indoles with nitroalkenes.Conidiogenone B is a kind of diterpenoid alkaloid with four highly fused rings and mulitiple chiral centers,so its total synthesis is difficult.This paper has two parts:?1?Friedel-Crafts reaction of nitroalkenes with indoles at the C7-position;?2?The total synthesis of Conidiogenone B.The specific research contents and results are as follows:?1?Friedel-Crafts reaction of nitroalkenes with indoles at the C7-positionThe first example of Friedel-Crafts reaction of indoles at the C7-position with nitroalkenes was developed by finishing the reaction of N-benzyl-1H-indol-4-amine and?E?-?2-nitrovinyl?benzene in alcohol under catalyst-free conditions.The exact structure of the product was confirmed by X-ray and the crystal datas was obtained from Rigaku ST Satum 724+diffractometer.On the basis of this reaction,we modified the structure of indoles to explore the effects of different factors on the reaction.At the same time,we synthesized 26 kinds of nitroalkenes and explored the adaptability of different substrates to this reaction.The experimental results showed that the reaction was suitable to most aromatic and heterocyclic substrates with high yields?68%-86%?.The derivative work was finished in high yields?76%-91%?:the nitro was reduced to amino in the condition of Raney-Ni and hydrazine hydrate,and the amino was protected by the group of Boc,then the benzyl protection was taken off in the condition of Pd/C and ammonium formate.?2?The total synthesis of Conidiogenone BThe total synthesis of Conidiogenone B which has four highly fused rings and six chiral centers needs several highly stereoselective steps.We designed a 15-step total synthetic route for achieving a more simple and efficient synthesis of this molecule.Isobutyraldehyde and tetrahydropyrrole were used as the starting materia.After the procedure of reflux and reduced pressure distillation,an enamine was obtained and started from it,followed by SN₂ reaction,catalytic hydrogenation,intramolecular Aldol reaction,the elimination of hydroxyl,the hydrolysis of methyl ester,the addition of a chiral auxiliary,1,4-addition reaction,alkylation,Huang ming long reaction,Wacker oxidation and Michael addition.We finished the route from SN₂ reaction to 1,4-addition reaction in 54%-94%yields and got the racemic product of 1,4-addition reaction in a total yield of 6.7%.In the attempt to alkylation reaction,some side reactions occurred because of the steric resistance.Due to the factors of difficulty and time,this total synthesis has not been completed.