Study On New Methods For The Tandem Cyclization Of 1,7-Enynes

The enyne cyclization reaction is the cyclizaiton of organic compounds that contain a C-C double bond and a C-C triple bond in one molecule. Transition metal-catalyzed carbocyclization of enyne are efficient and atom-economic methods to construct cyclic ring frameworks as one of the most important research fields in organic chemistry, which widely exist in nature products, biologically active molecules and new materials. The transition metal-catalyzed cyclization reaction of enynes, a concise and efficient method to construct C-C bonds, has several advantages, including(1) a convenient way to synthesis cyclic compounds, which is starting from open chain compounds with simple structure;(2) environmentally friendly and atom economical;(3) excellent selectivity(chemoselectivity, regioselectivity and stereoselectivity);(4) the formation of the special cyclic structures which is difficult to synthesis through conventional ways.Cyclic structures are widely found in nature products and biologically active molecule. The majority of complex cyclic molecules contain two or more rings. The transition metal-catalyzed cyclization of enyne has emerged as one of the most efficient ways to construct complex cyclic structure. Consequently, considerable efforts have been paid to develop new transition metal-catalyzed enyen cyclization methods. In order to enrich the diversity of the enyne cyclizaiton reaction and provide convenient route to the synthesis of cyclic compounds, we have develop some simple and efficient methods to achieve the 1,7-enyne cyclization reactions.This dissertation mainly focuses on transition metal-catalyzed cyclization of 1,7-enynes and activated alkenes, and the contents of this dissertation are as following:(1) Recent progress in the cyclization of 1,n-enyne are summarized in detail. Two part on the construction of cyclic structures are discussed in this chapter, including:(i) the cyclization of enyne without additional functional groups, such as skeleton rearrangement and cycloisomerization; and(ii) the cyclization of enyne with additional functional group. This chapter mainly described the catalytic system and the mechanism for the cyclization of enynes with functional groups.(2) A novel palladium-catalyzed 1,7-enyne cascade cyclization method to access spirocyclohexadienone-containing cyclopenta[c]quinolin-4(5H)-ones. This cascade cyclization method is achieved by the use of aryl diazonium salts and H2 O as the additional reagents through merger of 6-exo-dig cyclization and ipso-cyclization in one step. Most importantly, the results expand the scope and concept of transition-metal-catalyzed 1,7-enyne cyclization reactions, and the significance of the spirocyclohexadienone-containing cyclopenta[c]quinolin-4(5H)-one skeleton as a structural unit should make this method fascinating for organic and medicinal synthesis, thus providing new potential way for the construction of other complex heterocyclic architectures.(3) A new alkenyl-Cu strategy for the cascade cyclization of 1,7-enynes with aromatic sulfonyl chlorides. This reaction is operationally simple and represents a step-economical way to build molecular complexity with high functional group compatibility. Moreover, this method allows access to important benzo[j]phenanthridin-6(5H)-ones, thereby making this methodology more useful with wide potential applications in organic synthesis and medicinal chemistry.(4) A novel copper-catalyzed cascade cyclization of 1,7-enynes with metal sulfides is described. This sulfur-incorporation method provides straightforward access toward the important thiophene-fused quinolin-4(5H)-one scaffold through cyclization and double C-S bonds formation cascade, and the chemoselectivity of this 1,7-enyne cyclizaion toward 1,3,3a,9b-tetrahydrothieno[3,4-c]quinolin-4(5H)-ones and 3,3a-dihydrothieno[3,4-c]quinolin- 4(5H)-ones can be controlled by varying the sulfur resources.(5) One-pot self-assembly of the pyrrolo[4,3,2-de]quinolinone backbone through the cascade reaction strategy is lacking. We describe a new unprecedented cascade nitration/cyclization of 1,7-enynes with tBu ONO and H2 O for one-pot synthesis of pyrrolo[4,3,2-de]quinolinones. This method is achieved by cascade alkene nitration, 1,7-enyne 6-exo-trig cyclization, C-H nitrations and redox cyclization, and can be applicable to a wide range of 1,7-enynes with excellent functional group tolerance. The mechanism was also discussed according to the results of the in-situ HMRS analysis.(6) A novel tandem radical carbocyclization of N-(o-ethynylaryl)acrylamides with CH2Cl2 is described, the chemoselectivity of which toward cyclopenta[c]quinolin-4(5H)-ones and benzo[j]phenanthridin-6(5H)-ones relies on the substitution effect of the 2 position in N-(o-ethynylaryl)acrylamides. This method is successful by combining Ru catalysis, aryldiazonium salt initiation and visible light photoredox catalysis, and represents the first example of using CH2Cl2 as a one-carbon unit to construct the five-membered carbocyclic ring through multiple C-Cl/C-H functionalization and [2+2+1] annulation cascades.(7) A new visible light facilitated radical strategy for 1,2-alkylarylation of activated alkenes with a C(sp2)-H bond of arenes and a C(sp3)-H bond of alkyl halides. This method achieves selective scission of the C(sp3)-H bond adjacent to halide atoms leading to an halo-substituted alkyl radical, and provides a new synthetic utilization of aryl halides toward polyhalo-substituted oxindoles in good to excellent yields. Moreover, the concise transformation of the products, polyhalo-substituted oxindoles, into vinyl halides and alkynyl halides was also illustrated.