Aminohalogenation Of Functionalized Olefins

Aminohalogenation of olefins had intrigued chemists for decades as a very useful reaction,and it is attracting much more attention in the recent years for a number of new features.Aminohalogenation is a reaction with particular practical value.The vicinal haloamines could be synthesized by the intermolecular aminohalogenation which could be easily converted to amino acids,aziridine derivatives,amino alcohols and diamines etc.by interal or intra substituted reactions.On the other hand,intramolecular aminohalogention reactions are often used to build special nitrogen heterocyclics,such reactions are widely used in the total synthesis of natural products.The practical application of aminohalogention reactions has been restricted for the reasons that few functionalized olefin substrate and few sulfonamide nitrogen sources.In this thesis,benzyl carbamate and phthalimide were firstly developed as nitrogen sources for aminohalogenation of β-nitrostyrenes catalyzed by inorganic bases at room temperature.Also,we have developed β-dicyanostyrenes as a new class of functionalized olefins.Both of benzyl carbamate and phthalimide have been proved to be a good nitrogen source for this functionalized olefin.Furthermore,we have carried out a lot of work of deprotection and derivatization on part of the aminohalogenation products.Menthyl carbamate and chiral oxazolidinone were designed as two chiral nitrogen sources for the aminohalogenation of β-nitrostyrene,these chiral nitrogen-induced amine halogenation reactions have been explored.1.Aminohalogenation of β-nitrostyrenes by using benzyl carbamate(CbzNH2)as a new nitrogen sourceWe have researched the aminohalogenation of β-nitrostyrenes not only with benzyl carbamate as a new nitrogen source and N-chlorosuccinimide as chlorine source but also CbzNCl2 was used as nitrogen/chlorine source.Under the catalyzing of potassium carbonate,the opposite regioselectivity product 2,2-dichloro-2-nitro-1-benzyl carbon amide-1-aryl ethane was observed which is similar to the former work done by our group with TsNH2 as nitrogen,the result might be determined by the existence of the nitro group.The reaction was very convenient to carry out at room temperature within 8 hours which was faster than the sulfonamide as the nitrogen source.The yield of the reaction was best and almost all of the donors have given a yield more than ninety percents.Furthermore,some of them were nearly quantitative.The amino protection group Cbz of the product 1-lb was taken off under the existence of HBr(in acetic acid,30%w/w)and the resulted hydrogen bromide salt ofα,β primary amino dichloro nitro compound which could be conversed to 2-4c,an interesting imine.Diamine compound could be got under Pd/C catalytic hydrogenation condition with one-pot.The aminobromination of β-nitrostyrene was carried out with CbzNH2 as nitrogen source and NBS as bromine source with potassium phosphate as the catalyst.This reaction has good substrate adaptability,such as β-nitro-thiophene ethylene,β-nitrofuran ethylene and 1-nitro-1-nonene etc.could realize this reaction.Under the catalyzing of potassium phosphate,the opposite regioselectivity product 2,2-dibromo-2-nitro-1-benzyl carbon amide-1-aryl ethane was observed at room temperature.Almost all of the substrates could complete the reaction in 3 to 5 hours with the yield more than 80%.The amino protection group Cbz of the product 1-1d was taken off under the existence of HBr(in acetic acid,30%w/w)and the resulted hydrogen bromide salt of a β-primary amino dichloro nitro compound.All of the structures have been characterized by 1H NMR,13C NMR,HRMS and IR.The stereochemistry of product 2-lb and 2-ld were unambiguously confirmed by X-ray analysis.2.Aminohalogenation of β-nitrostyrenes by using phthalimide(PhthNH)as a new nitrogen sourceOur research work directly started with N-chloro-phthalimide as the nitrogen and halogen source.Through the exploration of the reaction,sodium hydroxide showed the best catalytic activity.Although the reaction conditions seem to be relatively harsh,the yield nearly more than 80%and the regioselectivity is also very well.Under Pd/C catalytic hydrogenation conditions,dichloro were stripped and nitro was restored,mainly generated ortho diamine compounds.To be surprised,we also got a byproduct of the amino aldehydes.This result led our amiohalogenation product derivative to the a-amino acetals and ortho diamine compounds which filled the gaps in the derivation of such kind of compounds.At last we eliminated the hydrogen halide under the base DABCO.All of the structures have been characterized by 1H NMR,13C NMR and HRMS.The stereochemistry of product 3-lb was unambiguously confirmed by X-ray analysis.3.Aminobromination of β-dicyanostyrenes by using benzyl carbamate(CbzNH2)as nitrogen sourceCyano is very useful functional which can be transformed to various other group under mild conditions.β-amino cyanide compounds are particularly useful intermediates,the dicyano compound could not only change to the single cyano nor to various heterocyclic structure.In this chapter,we designed β-dicyanostyrenes as a new kind of functionalized olefins for the aminohalogenation reaction.Based on the previous research,we chose the reaction system that benzyl carbamate as nitrogen source and NBS as halogen source which was very simple with a good response.Potassium phosphate was the best catalyst in this reaction.However,the results of the reaction were very satisfactory:short reaction time(3 h),high yield(more than 70%),good regioselectivity and so on.At last we eliminated the hydrogen halide under the base DABCO to get back to the β-dicyanostyrene with one more amino group.All of the structures have been characterized by 1H NMR,13C NMR,HRMS and IR.The stereochemistry of product 4-lb was unambiguously confirmed by X-ray analysis.4.Aminohalogenation of β-dicyanostyrenes by using phthalimide(PhthNH)as nitrogen sourceBased on the previous research above,we hope to expand phthalimide toβ-dicyanostyrenes as the nitrogen source in the aminohalogenation reaction.In this chapter we directly selected the best system with N-chloro-phthalimide as the nitrogen and chlorine source.Sodium hydroxide showed the best catalytic activity in the reaction.However,the reaction has a lot of advantages such as:short reaction time(0.5-3 h),high yield,good regioselectivity and so on.At last we eliminated the hydrogen halide under the base DABCO to get back to the β-dicyanostyrene with one more amino group.All of the structures have been characterized by 1H NMR,13C NMR and HRMS.The stereochemistry of product 5-lb was unambiguously confirmed by X-ray analysis.5.The exploration of chiral nitrogen source induced asymmetric aminohalogenationA new type of chiral nitrogen source based on the carbamate structure was designed for aminohalogenation reaction.Menthyl carbamate and chiral oxazolidine-2-ketone were firstly tried.Menthyl carbamate as the nitrogen source in the reaction gave the best yield of 95%while the de value was close to zero.(S)-N-Chloro-4-isopropyl-oxazolidine-2-one as the nitrogen chlorine source in the reaction gave the best yield of 76%while the best de value of 16%.This study provides a good strategy and research foundation work for the design of chiral nitrogen source.