Studies on the Development of Tandem Catalytic Reactions using Rh(II) Azavinyl Carbenes Derived from N-Sulfonyl-1,2,3-Triazoles

Abstract

The major purpose of the research presented in this thesis is the development of new tandem catalytic reactions using α-imino Rh(II)-carbenes, generated in situ from N-sulfonylated 1,2,3-triazoles, which can easily be synthesized by Cu(I)-catalyzed cycloaddition reactions of 1-alkynes and sulfonyl azides, known as ‘click’ reaction. Two different types of tandem reactions have been investigated. The first one is the sequential catalytic reaction comprised of a Cu(I)-catalyzed cycloaddition of 1-alkynes and sulfonyl azides, followed by a Rh(II)-catalyzed reaction of the resulting N-sulfonyl 1,2,3-triazoles with N,N-disubstituted formamides to provide cis-diamino enones with complete stereocontrol. Through intensive optimization experiments for the Rh(II)-catalyzed reaction of N-tosylated 4-phenyl-1,2,3-triazole with N,N-dimethyl formamide (DMF), it has been found that the triazole reacted efficiently with DMF in the presence of 1.3 mol% of Rh_(2)(^(t)BuCO_(2))_(4) in benzene solvent to afford cis-[β-N,N-dimethylamino α-N’-(p-toluenesulfonyl) amino]vinyl phenyl ketone in 81% yield. This reaction protocol showed broad substrate scope toward for both triazole and N,N-disubstituted formamide to afford various cis-diamino enones in good to excellent yields (55-91%). This transformation may proceed through the unprecedented formal stereoselective 1,2-insertion of α-imino Rh(II)-carbenes into the C=O bond of formamides. It has also been demonstrated that the sequential tandem reaction of the Cu(I)-catalyzed cycloaddition reaction of an alkyne and a sulfonyl azide, followed by a Rh(II)-catalyzed reaction of the resulting triazole with DMF could be possible to allow the one-pot synthesis of cis-diamino enones in overall 61% yield. The other type of reaction is the Rh(II)-catalyzed reaction of N-sulfonyl 1,2,3-triazoles with β-enamino esters affording 2,5-dihydro-1H-imidazoles (3-imidazolines) with broad functional group tolerance. Mechanistic studies using deuterium-labeled triazoles suggest that the reaction proceeds in a cascade through the N-H insertion of an α-imino Rh(II)-carbene, followed by enamine-imine tautomerization and conjugate addition. Moreover, the reaction proceeds with high diastereoselectivity for α-substituted β-enamino esters to give a single diastereomer. The reaction can also be carried out in a tandem one-pot fashion starting from a sulfonyl azide and a terminal alkyne, avoiding isolation of triazole to minimize generation of waste.;졸업논문 연구의 가장 큰 목적은 α-imino Rh(Ⅱ)-carbene을 사용한 다단계 연속촉매반응 개발이다. 논문에서 쓰이는 α-imino Rh(Ⅱ)-carbene은 1-alkyne과 sulfonyl azide가 구리촉매하에서 cycloaddition 반응을 통해 만들어지는 N-sulfonyl 1,2,3-triazole의 ring-chain tautomerization으로 쉽게 형성되는 물질이다. 우선 연구는 두 가지 종류의 다단계 연속반응을 중점으로 진행되었다. 첫 연구주제는 구리 촉매로 만들어진 triazole을 Rh 촉매하에서 N,N-dialkyl formamide와 반응시켜 구조 선택적인 cis-diamino enone을 만드는 반응이다. 1.3 mol% Rh_(2)(^(t)BuCO_(2))_(4)촉매 와 벤젠 수용액 조건하에서 원하는 cis-diamino enone 생성물을 81%의 최적화된 수득률로 얻었고, 다양한 substrate scope에서 대부분 통용되었다. 이 반응에서는 α-imino Rh(Ⅱ)-carbene이 formamide의 C=O bond가 입체선택적으로 1,2-insertion을 함으로서 일어난다. 선택적인 다단계 연속촉매반응을 진행하면, 구리조건하에서 triazole이 형성되고, 그 다음 Rh 촉매와 반응해 결국 원하는 생성물인 cis-diamino enine을 종합적으로 61%의 수득률로 얻을 수 있었다. 두번째 연구주제는 triazole을 Rh 촉매하에서 β-enamino ester와 반응시켜 2,5-dihydro-1H-imidazole 생성물을 얻는 것이다. 이 반응은 mechanistic 연구를 통해 반응메커니즘이 α-imino Rh(Ⅱ)-carbene에 아민의 N-H insertion이 일어나고 연속적으로 enamine-imine tautomerization과 conjugate addition을 통해 생성물을 얻어낸다. 이 두 반응 모두 결과적으로는 한 반응용기안에서 여러 촉매를 이용해서 반응이 일어나는 다단계연속반응을 한 층 더 개발시키는 역할을 한다.