Three-Component Cycloadditions:  The First Transition Metal-Catalyzed [5+2+1] Cycloaddition Reactions

Abstract

Prompted by our studies of transition metal-catalyzed [4+4], [4+2], [5+2], and [6+2] cycloadditions and by the view that these two-component reactions could be intercepted by a third component of one or more atoms, a new three-component transition metal-catalyzed cycloaddition is described. This new [5+2+1] cycloaddition proceeds in good to excellent yield and with high or complete regioselectivity with a variety of carbonyl-substituted alkynes to give bicyclo[3.3.0]octenone adducts, resulting from transannular closure of the intermediate eight-membered-ring cycloadduct. Effects of concentration, temperature, pressure, and catalyst loading on the efficiency of the reaction are discussed. This process provides access to complex building blocks for synthesis based on simple, readily available components.

Rhodium‐Catalyzed [4+2+2] Cycloaddition Reaction of Two Enynes or Diynes with One Diene to Give Eight‐Membered Ring Compounds

“…[5i] conducted the catalytic reaction using [RhA C H T U N G T R E N N U N G (NBD)Cl] 2 /AgSbF 6 /Me-DuPHOS in the mixed solvent CH 2 Cl 2 and EtOAc (6:1) at 60 8C for 12 h. The combined yield of 1b and 1b' and the ratio of 1b:1b' were highly dependent upon the counteranion (entries 2-5) and the reaction medium (entries [5][6][7][8]. Interestingly, when acetonitrile was used as a solvent (entry 6), no reaction was observed.…”

“…However, the known transition metal-catalyzed [4 + 2 + 2] reactions are bimolecular and three-component cycloadditions of enynes with 1,3-butadiene, diynes with alkynes, diynes with 1,3-butadienes, diene-enes with alkynes, or dienynes to dimers. Although there have been many reports on trimolecular cycloadditions, such as [5 + 2 + 1], [6] [2 + 2 + 2], [7] and, [4 + 4 + 1] [8] cycloadditions, trimolecular [4 + 2 + 2] cycloadditions catalyzed by transition metals have not been forthcoming. Very recently, a three-molecular [3 + 2 + 2] cycloaddition of ethyl cyclopropylideneacetate and alkynes has been reported.…”

Silicon‐Initiated Carbonylative Carbotricyclization and [2 + 2 + 2 +1] Cycloaddition of Enediynes Catalyzed by Rhodium Complexes.

“…This reaction is believed to proceed through a series of metallacycles. The proposed mechanism includes (i) selective coordination of the diyne moiety of enediyne 7 to the active Rh-catalyst species, forming metallacycle A 13 ([2+2+M]), (ii) insertion of the olefin moiety of 7 into the Rh-C bond to form 5-7-5 fused tricyclic rhodacycle B 13 ([2+2+2+M]), (iii) coordination of CO to the [Rh] metal followed by migratory insertion of CO into the Rh-C bond to form 5-8-5 rhodacycle C 13 or D 13 ([2+2+2+1+M]), and (iv) reductive elimination to form [2+2+2+1] cycloadduct 8 and regenerate the active Rh-catalyst species. Reductive elimination from the 5-7-5 rhodacycle B 13 , prior to the CO insertion, gives [2+2+2] cycloadduct 17.…”

Intermolecular Dienyl Pauson–Khand Reaction

“…[1] Our studies toward this objective have thus far resulted in new metal-catalyzed [4+4], [2] [4+2], [3] [5+2], [4] and [6+2] [5] cycloadditions and three-component [5+2+1], [6] [4+2+1], and [2+2+1] reactions. [7] In the course of our studies on the rhodium(i)-catalyzed intramolecular dienyl [2+2+1] Pauson-Khand reaction, we observed that when a diene is used in place of an alkene the reaction rate is significantly accelerated.…”

“…Table 2 summarizes the effect of alkyne structure on the reaction. Various functionalities are tolerated, and under optimal conditions several alkynes underwent the desired reaction to provide the corresponding [2+2+1] cycloadducts in excellent yields (> 85 %; Table 2, entries [1][2][3][4]6). The reaction of the differentially substituted alkyne 6 proceeded in a completely regioselective fashion ( Table 2, entry 2), whereas the reaction of the n-pentyl-substituted alkyne 8 gave a 1:1.6 mixture of regioisomeric products 9 a and 9 b (Table 2, entry 3).…”