Fused tetracycles with a benzene or cyclohexadiene core: [2 + 2 + 2] cycloadditions on macrocyclic systems

Abstract

A series of fused tetracycles with a benzene or cyclohexadiene core (2a-h) is satisfactorily prepared by intramolecular [2 + 2 + 2] cycloadditions of triynic and enediynic macrocycles (1a-h) under RhCl(PPh3)3 catalysis; the enantioselective cycloaddition of macrocycles 1b and 1e and gives chiral tetracycles with moderate enantiomeric excess.

Rhodium(I)‐Catalysed Intramolecular [2+2+2] Cyclotrimerisations of 15‐, 20‐ and 25‐Membered Azamacrocycles: Experimental and Theoretical Mechanistic Studies

“…Cyclisation of 10 with 1,4-dibromo-2-butyne in the presence of K 2 CO 3 as a base afforded a 60 % yield of macrocycle 3 a. When intermediate 10 was condensed with the dichloro derivative 11 a, previously prepared by us, [8] 25-membered pentaacetylenic macrocycle 4 was obtained with an almost quantitative yield. The p-tolylsulfonamide units give a high level of insolubility in the most common organic solvents in the 20-membered macrocycle.…”

“…To introduce an arylic unit that was different to the other three and to prepare 3 b, an alternative synthetic route was used (see Scheme 2). Condensation between dichloro derivative 11 b, [8] which introduces the differential aryl unit, and trisulfonamide 12 a [6] afforded a 96 % yield of macrocycle 3 b. Reaction of 12 b [6] with 11 b [8] gave macrocycle 3 c containing four units of 2,4,6-triisopropylphenyl.…”

“…[ [5][6][7][8] When 20-membered macrocycles 3 a-c, heated under reflux in toluene, were treated with [RhCl-…”

“…Partially intramolecular approaches or fully intramolecular cycloaddition processes represent efficient entries into various multiple-fused ring compounds. Over the last few years, we have developed an efficient rhodium(I)-catalysed [2+2+2] cyclotrimerisation process of 15-, 16-and 17-membered triynic and enediynic azamacrocycles of type 1 (to give compounds 2) and have described the first examples in the literature of completed closed systems [5][6][7][8] (Scheme 1). To broad-…”

[2+2+2] Cycloaddition Reactions of Macrocyclic Systems Catalyzed by Transition Metals. A Review

“…In recent years our group has been interested in the synthesis and applications of polyalkyne and enediyne azamacrocyclic systems [ 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Early on we observed that the [2+2+2] cycloisomerization of the closed derivatives could easily result in highly functionalized tetracyclic fused structures in one-pot and atom-economical process.…”